<?xml version="1.0" encoding="UTF-8" standalone="no"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<article xml:lang="EN" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2023.1181942</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Nutrition</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Integrating LC-MS and HS-GC-MS for the metabolite characterization of the Chinese medicinal plant <italic>Platostoma palustre</italic> under different processing methods</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Tang</surname> <given-names>Danfeng</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/906698/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Quan</surname> <given-names>Changqian</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Huang</surname> <given-names>Suhua</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Wei</surname> <given-names>Fan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/2236948/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants</institution>, <addr-line>Nanning</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>National Traditional Chinese Medicine Inheritance and Innovation Center, Guangxi Botanical Garden of Medicinal Plants</institution>, <addr-line>Nanning</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>College of Pharmacy, Guangxi Medical University</institution>, <addr-line>Nanning</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Leandro De Morais Cardoso, Juiz de Fora Federal University, Brazil</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Nannan Zhang, Guangdong Academy of Sciences, China; Nguyen Cong-Hau, Nguyen Tat Thanh University, Vietnam; Mohamed Ashour, National Institute of Oceanography and Fisheries (NIOF), Egypt</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Fan Wei <email>wfmanuscript&#x00040;163.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>19</day>
<month>05</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>10</volume>
<elocation-id>1181942</elocation-id>
<history>
<date date-type="received">
<day>08</day>
<month>03</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>18</day>
<month>04</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2023 Tang, Quan, Huang and Wei.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Tang, Quan, Huang and Wei</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license> </permissions>
<abstract>
<p><italic>Platostoma palustre</italic> (or <italic>Mesona chinensis</italic> Benth) is an important medicinal and edible plant in China and Southeast Asian countries. To study the effects of different processing methods on the quality, nutrition, and flavor of <italic>P. palustre</italic>, we adopted the LC-MS and HS-GC-MS to compare the influences of tedding (S), sweating (M), and drying (H) on the metabolites and volatile substances of <italic>P. palustre</italic>. Biochemical determinations revealed that the M treatment could promote the accumulation of the contents of total sugar, soluble sugar, and total pectin compared with the H and S treatments but decrease the total flavonoid contents. LC-MS and HS-GC-MS uncovered 98 differential metabolites and 27 differential volatile substances among the three treatments, respectively. Overall, the M treatment facilitated the stabilization and improvement of the quality of polysaccharides and volatile substances, while the H treatment could promote the level of amino acids in <italic>P. palustre</italic>. The current study provided a theoretical reference for establishing standardized processing methods and sustaining the quality stability of <italic>P. palustre</italic> in future.</p></abstract>
<kwd-group>
<kwd><italic>Platostoma palustre</italic></kwd>
<kwd>processing methods</kwd>
<kwd>LC-MS</kwd>
<kwd>HS-GC-MS</kwd>
<kwd>metabolites</kwd>
<kwd>volatile substances</kwd>
</kwd-group>
<counts>
<fig-count count="6"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="98"/>
<page-count count="18"/>
<word-count count="11715"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Food Chemistry</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1. Introduction</title>
<p><italic>Platostoma palustre</italic> (or <italic>Mesona chinensis</italic> Benth), also known as &#x0201C;Xiancao,&#x0201D; is an annual herb of the Labiatae family, which is distributed in the provinces of Guangxi, Guangdong, Taiwan, Zhejiang, and Jiangxi in China (<xref ref-type="bibr" rid="B1">1</xref>). <italic>P. palustre</italic> is an important medicinal and edible plant (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B3">3</xref>), with the above-ground part or the whole plant constituting its medicinal parts. According to the records of &#x0201C;Chinese Materia Medica&#x0201D; and &#x0201C;Dictionary of Traditional Chinese Medicine,&#x0201D; <italic>P. palustre</italic> is effective in treating thirst and hypertension (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>). Modern research reports that <italic>P. palustre</italic> possesses antioxidation (<xref ref-type="bibr" rid="B6">6</xref>), antihypertensive (<xref ref-type="bibr" rid="B7">7</xref>), antibiosis (<xref ref-type="bibr" rid="B8">8</xref>), and hypolipidemic effects (<xref ref-type="bibr" rid="B9">9</xref>). <italic>P. palustre</italic> is rich in polysaccharides, flavonoids, phenolic acid, volatile oil, and other components (<xref ref-type="bibr" rid="B10">10</xref>). Among those, polysaccharides (or xiancao gum) represent one of the most important quality indicators of <italic>P. palustre</italic> (<xref ref-type="bibr" rid="B11">11</xref>), and volatile oil endows the species with a special flavor quality (<xref ref-type="bibr" rid="B12">12</xref>). At present, <italic>P. palustre</italic> is mainly used to produce herbal tea and jelly. With the development of the herbal tea industry, new products made of <italic>P. palustre</italic> are becoming increasingly popular, thus gradually making it a research hotspot (<xref ref-type="bibr" rid="B13">13</xref>).</p>
<p>Generally, the quality of traditional Chinese medicine (TCM) is affected by many factors, such as the variety, origin, harvesting, storage, processing methods, and extraction of the effective components of TCM. Among these, the processing methods include pretreatment, processing, and pulverization of TCM (<xref ref-type="bibr" rid="B14">14</xref>). Sweating (micro-fermentation) treatment is the primary processing method for many TCM. <italic>Magnolia officinalis</italic> has a brown surface, and its cross-section turns purplish-red after sweating treatment and the content of magnolol increases while the content of volatile oil and alkaloids decreases (<xref ref-type="bibr" rid="B15">15</xref>). The sweating treatment of <italic>Poria cocos</italic> after traditional sweating is whiter with better lustre compared with that after steaming, improving the water solubility of its polysaccharides (<xref ref-type="bibr" rid="B16">16</xref>). Tedding refers to use the heat emitted by the sun to evaporate water from medicinal materials, while the traditional drying method involves setting up a simple drying room, using outdoor auxiliary equipment to heat the room, and an exhaust fan to extract the generated moisture outside. Both of these methods are necessary steps for the primary processing of many TCM.</p>
<p>In fact, sweating treatment is also the primary processing method in the <italic>P. palustre</italic> industry. The whole herb medicine of <italic>P. palustre</italic> is usually harvested before flowering. After harvesting and proper drying, the sweating treatment should be carried out in the production area. Subsequently, through the sweating treatment by stacking, the final herbal medicine of <italic>P. palustre</italic> would be brownish or brown in color, having a unique aroma (<xref ref-type="bibr" rid="B17">17</xref>). Lu (<xref ref-type="bibr" rid="B18">18</xref>) reported that there were some differences in the total flavonoids and total sugar content of <italic>Mesina chinensis Benth</italic> with different (micro-fermentation, shade drying, and oven drying) processing methods, and the content of total flavonoids in <italic>M. chinensis</italic> treated by micro-fermentation was found to be lower than that in the dried samples. However, there was no obvious difference between the volatile components of the sample of micro-fermentation and the dry samples, but after fermentation was performed two times, the relative content of caryophyllene in the samples decreased significantly (&#x003B2;-caryophyllene 0.85% and &#x003B1;-caryophyllene 0.37%), while fora-selinene and &#x003B2;-selinene had little effect (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B18">18</xref>).</p>
<p>Up to now, there have been few comprehensive reports on the effects of processing methods on the metabolites and volatile substances of <italic>P. palustre</italic>. Therefore, in this study, we compared and analyzed the effects of different (tedding, drying, and sweating) processing treatments on the metabolites and volatile substances of <italic>P. palustre</italic>. Here, we adopted the LC-MS and HS-GC-MS methods to compare the effects of tedding, sweating, and drying on the quality and flavor of <italic>P. palustre</italic>, thus providing a theoretical reference for establishing standardized processing methods and maintaining the quality stability of <italic>P. palustre</italic> in future.</p></sec>
<sec id="s2">
<title>2. Materials and methods</title>
<sec>
<title>2.1. Sample preparation</title>
<p>The <italic>P. palustre</italic> plants from the same variety (Lingshan) and fields were harvested on 25 July 2022. Subsequently, the fresh plant materials were treated with sweating (M), tedding (S), and drying (H), respectively (<xref ref-type="fig" rid="F1">Figure 1</xref>). Sweating (M) method: Collect the aerial part of <italic>P. palustre</italic>, remove the roots and redundant soil, and spread and ted the materials in the field. When the materials wither to dark green and lose &#x0007E;&#x000BD; of their water content, bundle, stack, and seal the materials with transparent plastic film on the cement ground. Soak the package in the sun for 1 or 2 days, remove the film, spread out, and dry the materials until the stems are fragile, the leaves are slightly flexible, and the water content is &#x0007E;13&#x02013;15%. Tedding (S) method: The initial procedure is the same as above. When the materials wither to a dark green color and lose half of their water, transfer them to a cement ground to continue tedding (turn it over every 2 h) until the stems are fragile, the leaves are slightly flexible, and the water content is &#x0007E;13&#x02013;15%. Cover them with plastic film in the evening to prevent rain. Drying (H) method: Place the fresh plant materials in the oven and dry at a low temperature of 50&#x000B0;C until the moisture content is &#x0007E;13&#x02013;15%. Cut the processed materials into small sections, then grind them into powder, and sieved them with a 200 mesh sieve. All samples were used for subsequent analysis.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Schematic diagram of the experimental treatment flow in this study.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-10-1181942-g0001.tif"/>
</fig></sec>
<sec>
<title>2.2. Biochemical determination</title>
<p>The contents of total sugar, soluble sugar, total pectin, and total flavonoid were detected using the total sugar content kit (G0503F), soluble sugar content kit (G0501F), total pectin content kit (G0717F), and total flavonoid kit (G0118F), respectively (Grace Biotechnology, <ext-link ext-link-type="uri" xlink:href="http://geruisi-bio.com/">http://geruisi-bio.com/</ext-link>, Suzhou, China). All the kits were measured using a spectrophotometer method.</p></sec>
<sec>
<title>2.3. UHPLC-MS/MS analysis</title>
<p>A total of six biological replicates were used per treatment. The metabolite extraction was utilized for LC/MS analysis (<xref ref-type="bibr" rid="B19">19</xref>), with minor adjustments, and a bioinformatic analysis was carried out at Shanghai Majorbio Co., Ltd. (<ext-link ext-link-type="uri" xlink:href="http://wwwmajorbiocom/">http://wwwmajorbiocom/</ext-link>) following standard procedures.</p>
<sec>
<title>2.3.1. Metabolite extraction</title>
<p>In total, 50 mg of powder samples were accurately weighed, and the metabolites were extracted using a 400 &#x003BC;L methanol: water (4:1, v/v) solution with 0.02 mg/mL L-2-chlorophenylalanin as an internal standard. The mixture was allowed to settle at &#x02212;10&#x000B0;C, treated by high-throughput tissue crusher Wonbio-96c (Shanghai Wanbo Biotechnology Co., LTD) at 50 Hz for 6 min, and then followed by ultrasound at 40 kHz for 30 min at 5&#x000B0;C. The samples were placed at &#x02212;20&#x000B0;C for 30 min to precipitate proteins. After centrifugation at 13,000 &#x000D7; <italic>g</italic> at 4&#x000B0;C for 15 min, the supernatant was carefully transferred to sample vials for LC-MS/MS (UHPLC-Q Exactive HF-X system, Thermo Fisher Scientific) analysis.</p></sec>
<sec>
<title>2.3.2. Quality control sample</title>
<p>As a part of the system conditioning and quality control process, a pooled quality control (QC) sample was prepared by mixing equal volumes of all samples. The QC samples were disposed of and tested in the same manner as the analytic samples, thereby helping to represent the whole sample set, which was injected at regular intervals (every 5&#x02013;15 samples), in order to monitor the stability of the analysis.</p></sec>
<sec>
<title>2.3.3. Chromatographic conditions</title>
<p>In total, 2 &#x003BC;L of the sample was separated by an HSS T3 column (100 mm &#x000D7; 2.1 mm i.d., 1.8 &#x003BC;m) and then entered into mass spectrometry detection. The mobile phases consisted of 0.1% formic acid in water:acetonitrile (95:5, v/v; solvent A) and 0.1% formic acid in acetonitrile:isopropanol:water (47.5:47.5:5, v/v; solvent B). The solvent gradient changed according to the following conditions: from 0 to 3.5 min, 0% B to 24.5% B (0.4 mL/min); from 3.5 to 5 min, 24.5% B to 65% B (0.4 mL/min); from 5 to 5.5 min, 65% B to 100% B (0.4 mL/min); from 5.5 to 7.4 min, 100% B to 100% B (0.4 to 0.6 mL/min); from 7.4 to 7.6 min, 100% B to 51.5% B (0.6 mL/min); from 7.6 to 7.8 min, 51.5% B to 0% B (0.6 to 0.5 mL/min); from 7.8 to 9 min, 0% B to 0% B (0.5 to 0.4 mL/min); and from 9 to 10 min, 0% B to 0% B (0.4 mL/min) for equilibrating the systems. The sample injection volume was 2 &#x003BC;L, and the flow rate was set to 0.4 mL/min, with the column temperature maintained at 40&#x000B0;C. During the period of analysis, all these samples were stored at 4&#x000B0;C.</p></sec>
<sec>
<title>2.3.4. MS conditions</title>
<p>The mass spectrometric data were collected using a Thermo UHPLC -Q Exactive HF-X Mass Spectrometer, equipped with an electrospray ionization (ESI) source operating in either positive or negative ion modes. The optimal conditions were set as followed: heater temperature, 425&#x000B0;C; capillary temperature, 325&#x000B0;C; sheath gas flow rate, 50 arb; aux gas flow rate, 13 arb; ion-spray voltage floating (ISVF), &#x02212;3,500 V in negative mode, and 3,500 V in positive mode, respectively. Normalized collision energy and 20-40-60V rolling were employed for MS/MS. Full MS resolution was 60,000, and MS/MS resolution was 7,500. Data acquisition was performed using the Data Dependent Acquisition (DDA) mode. The detection was carried out over a mass range of 70&#x02013;1,050 m/z.</p></sec>
<sec>
<title>2.3.5. Data preprocessing and annotation</title>
<p>After the mass spectrometry detection was completed, the raw data of LC/MS were preprocessed by Progenesis QI software (Waters Corporation, Milford, USA), and a three-dimensional data matrix in CSV format was exported. The information in this three-dimensional matrix included as follows: sample information, metabolite name, and mass spectral response intensity. Internal standard peaks and any known false positive peaks (including noise, column bleed, and derivatized reagent peaks) were removed from the data matrix, deredundant, and peak pooled. At the same time, the metabolites were searched and identified, with the main databases being the HMDB (<ext-link ext-link-type="uri" xlink:href="http://www.hmdb.ca/">http://www.hmdb.ca/</ext-link>), Metlin (<ext-link ext-link-type="uri" xlink:href="https://metlin.scripps.edu/">https://metlin.scripps.edu/</ext-link>), and Majorbio databases.</p>
<p>The data obtained after the database search were uploaded to the Majorbio cloud platform (<ext-link ext-link-type="uri" xlink:href="https://cloud.majorbio.com">https://cloud.majorbio.com</ext-link>) for further analysis. Metabolic features detected in at least 80% of any set of samples were retained. After filtering, minimum metabolite values were imputed for specific samples, in which the metabolite levels fell below the lower limit of quantitation, and each metabolic feature was normalized by sum normalization. To reduce the errors caused by sample preparation and instrument instability, the response intensity of the sample mass spectrum peaks was normalized by the sum normalization method, thereby obtaining the normalized data matrix. At the same time, variables with relative standard deviation (RSD) &#x0003E; 30% of QC samples were removed, and log10 logarithmic transformation was performed to obtain the final data matrix for subsequent analysis.</p></sec>
<sec>
<title>2.3.6. Differential metabolites analysis</title>
<p>Variance analysis was performed on the matrix file after data preprocessing. The R package ropls (version 1.6.2) was used to perform principal component analysis (PCA) and orthogonal least partial squares discriminant analysis (OPLS-DA), and a seven-cycle interactive validation was used to evaluate the stability of the model. In addition, the Student&#x00027;s <italic>t</italic>-test and fold difference analysis were carried out. The selection of significantly different metabolites was determined based on the variable importance in the projection (VIP) obtained by the OPLS-DA model and the <italic>p</italic>-value of the Student&#x00027;s <italic>t</italic>-test, and the metabolites with VIP &#x0003E; 1 and <italic>p</italic> &#x0003C; 0.05 were significantly different metabolites (<xref ref-type="bibr" rid="B20">20</xref>).</p>
<p>Differential metabolites among the two groups were summarized and mapped into their biochemical pathways through metabolic enrichment and pathway analysis based on a database search (KEGG, <ext-link ext-link-type="uri" xlink:href="http://www.genome.jp/kegg/">http://www.genome.jp/kegg/</ext-link>). Scipy.stats (Python packages; <ext-link ext-link-type="uri" xlink:href="https://docs.scipy.org/doc/scipy/">https://docs.scipy.org/doc/scipy/</ext-link>) was exploited to identify statistically significantly enriched pathways using Fisher&#x00027;s exact test.</p></sec></sec>
<sec>
<title>2.4. HS-GC-MS analysis</title>
<p>In this study, six biological replicates were also employed per treatment. The extraction of volatile substances was used for HS-GC-MS analysis as per the method of Dong et al. (<xref ref-type="bibr" rid="B21">21</xref>), with minor modifications, and a bioinformatic analysis was carried out at Shanghai Majorbio Co., Ltd. (<ext-link ext-link-type="uri" xlink:href="http://wwwmajorbiocom/">http://wwwmajorbiocom/</ext-link>), followed by standard procedures.</p>
<sec>
<title>2.4.1. Extraction</title>
<p>Accurately, 3 g of the sample was weighed and placed into a 20 ml headspace bottle, and then the headspace bottle was immediately sealed until the analysis.</p></sec>
<sec>
<title>2.4.2. HS-GC-MS analysis</title>
<p>The analysis was performed using an Agilent 8890B gas chromatography, with a 7697A headspace sampler coupled to an Agilent 7000D mass selective detector with an inert electron impact (EI) ionization source and ionization voltage was 70 eV (Agilent, USA). Analyte compounds were separated with a VF-WAXms (25 m &#x000D7; 0.25 mm &#x000D7; 0.2 &#x003BC;m) capillary column, using 99.999% helium as a carrier gas at a constant flow rate (1 mL/ min). The temperature of the headspace strip heating box was 130&#x000B0;C, the quantitative ring was 150&#x000B0;C, the transmission line was 170&#x000B0;C, the balance time of the sample bottle was 20 min, and the GC cycle time was 35 min. The GC column temperature was programmed to hold at 40&#x000B0;C for 2 min and rose to 100&#x000B0;C at a rate of 5&#x000B0;C per minute, then rose to 230&#x000B0;C at a rate of 15&#x000B0;C per minute, for 5 min. The injection volume of samples was 1 &#x003BC;L and introduced in splitting mode (10:1) with the inlet temperature of 180&#x000B0;C. The ion sources temperature was 230&#x000B0;C, and the quadrupole temperature was 150&#x000B0;C. The scanning mode was full scan mode, the quality scanning range was 30&#x02013;1,000 m/z, and the scanning frequency was 3.2 scan/s.</p></sec>
<sec>
<title>2.4.3. Quality control</title>
<p>To evaluate the stability of the analytical system during the run-on process, a quality control (QC) sample was prepared during the experiment. QC samples were prepared by mixing all test samples and were handled in the same way as the formal samples. During instrument testing, a QC sample was inserted every 5&#x02013;15 samples. The repeatability of QC samples reflects the stability of the instrument in the whole analysis process. At the same time, it can also be used to identify variables with significant variations in the analysis system to ensure the reliability of the results.</p></sec>
<sec>
<title>2.4.4. Data preprocessing and annotation</title>
<p>After the mass spectrometry detection was completed, the raw data of GC/MS were preprocessed by MassHunter Workstation Quantitative Analysis (v10.0.707.0) software, and a three-dimensional data matrix in CSV format was exported. The internal standard peaks and any known false positive peaks were removed from the data matrix, deredundant, and peak pooled. Meanwhile, the metabolites were searched and identified, and the main database used was the Fiehn and NIST public databases.</p>
<p>The data after being retrieved from the database search were uploaded to the Majorbio cloud platform (<ext-link ext-link-type="uri" xlink:href="https://cloud.majorbio.com">https://cloud.majorbio.com</ext-link>) for analysis. Metabolic features detected at least 80% in any set of samples were retained. After filtering, minimum metabolite values were imputed for specific samples, in which the metabolite levels fell below the lower limit of quantitation, and each metabolic feature was normalized by sum. To reduce the errors caused by sample preparation and instrument instability, the response intensity of the sample mass spectrum peaks was normalized by the sum normalization method, thus obtaining a normalized data matrix. At the same time, variables with relative standard deviation (RSD) &#x0003E; 30% of QC samples were removed, and log10 logarithmization was performed to obtain the final data matrix for subsequent analysis.</p></sec>
<sec>
<title>2.4.5. Differential metabolites analysis</title>
<p>Variance analysis was conducted on the matrix file after data preprocessing. The R package ropls (version 1.6.2) was used to perform principal component analysis (PCA) and orthogonal least partial squares discriminant analysis (OPLS-DA), and a seven-cycle interactive validation was used to evaluate the stability of the model. In addition, Student&#x00027;s <italic>t</italic>-test and fold difference analysis were performed. The selection of significantly different metabolites was determined based on the variable importance in the projection (VIP), obtained by the OPLS-DA model and the <italic>p</italic>-value of Student&#x00027;s <italic>t</italic>-test, and the metabolites with VIP &#x0003E; 1 and <italic>p</italic> &#x0003C; 0.05 were considered to be significantly different metabolites (<xref ref-type="bibr" rid="B20">20</xref>).</p></sec></sec>
<sec>
<title>2.5. Statistical analysis</title>
<p>SPSS 17.0 software was employed for statistical analysis, and the data means were analyzed using the Duncan test for statistical significance (<italic>p</italic> &#x0003C; 0.05). Each test was analyzed independently, and the test for homogeneity of variance was performed prior to ANOVA. GraphPad Prism 7 and WPS software were used for data processing and graphic analysis.</p></sec></sec>
<sec id="s3">
<title>3. Results</title>
<sec>
<title>3.1. Influence of different processing methods on the quality of <italic>P. palustre</italic></title>
<p>As shown in <xref ref-type="fig" rid="F2">Figure 2</xref>, compared with the sweating (M) treatment, the total sugar contents significantly decreased by 19.9 and 14.5% in the drying (H) and tedding (S) treatments, respectively. Meanwhile, the soluble sugar contents dramatically reduced by 10.4 and 14.2%, and the total pectin contents significantly decreased by 18.9 and 8.9% in H and S treatments, respectively. However, the total flavonoid contents in H and S treatments significantly increased by 91.2 and 36.5% in comparison with the M treatment.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p>Comparison of total sugar, soluble sugar, total pectin, and total flavonoids under different treatments. The treatments containing the same letters indicated no significant differences (<italic>p</italic> &#x0003E; 0.05), while the treatments containing different letters indicated significant differences (<italic>p</italic> &#x0003C; 0.05).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-10-1181942-g0002.tif"/>
</fig></sec>
<sec>
<title>3.2. Metabolites of different treatments based on LC-MS</title>
<p>In this study, the metabolites were extracted from the aerial part of <italic>P. palustre</italic> plants, with six replicates of each treatment, and analyzed based on LC-MS. A total of 1,591 and 1,595 metabolites were identified under the positive and negative ion scanning modes, respectively (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 1</xref>). Analysis of correlation, PCA, Venn, and PLS-DA showed that the data were reliable (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 2</xref>). Based on these metabolites, the Kyoto Encyclopedia of Genes and Genomes (KEGG) compound classification revealed that a total of 174 metabolites could be categorized as phospholipids, monosaccharides, fatty acids, carboxylic acids, eicosanoids, amino acids, and vitamins (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 3A</xref>; <xref ref-type="supplementary-material" rid="SM2">Supplementary Tables 1</xref>, <xref ref-type="supplementary-material" rid="SM2">2</xref>). Further analysis of the KEGG pathway showed that they were involved in lipid metabolism, carbohydrate metabolism, biosynthesis of other secondary metabolites, amino acid metabolism, and metabolism of cofactors and vitamins (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 3B</xref>).</p></sec>
<sec>
<title>3.3. Differential metabolites analysis</title>
<p>In this study, the three groups could be better distinguished by OPLS-DA analysis in both positive and negative modes, and the OPLS-DA model was feasible, and the metabolites also differed significantly between the three comparison groups (<xref ref-type="fig" rid="F3">Figures 3A</xref>&#x02013;<xref ref-type="fig" rid="F3">C</xref>). All the identified metabolites were used for screening differential metabolites according to the VIP &#x0003E; 1 and <italic>p</italic> &#x0003C; 0.05, and the results of the three comparison groups are presented in <xref ref-type="fig" rid="F3">Figures 3D</xref>&#x02013;<xref ref-type="fig" rid="F3">F</xref>. A total of 1,594 differential metabolites were identified among the H, M, and S treatments (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 4</xref>). Of these, a total of 1,050, 1,036, and 956 differential metabolites were identified in H vs. M, H vs. S, and S vs. M comparisons, respectively (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figures 5A</xref>&#x02013;<xref ref-type="supplementary-material" rid="SM1">C</xref>). Based on these differential metabolites, the analysis of KEGG compounds classification showed that a total of 98 differential metabolites were detected among the three treatments (<xref ref-type="table" rid="T1">Table 1</xref>). Among these, there were 62, 53, and 69 differential metabolites in H vs. M, H vs. S, and S vs. M comparisons, respectively, which mainly included phospholipids, carboxylic acids, monosaccharides, amino acids, and vitamins (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figures 5D</xref>, <xref ref-type="supplementary-material" rid="SM1">E</xref>). Furthermore, KEGG enrichment analysis revealed that a total of 85, 79, and 46 differential metabolites in H vs. M, H vs. S, and S vs. M comparisons were significantly enriched in different pathways, respectively (<italic>p</italic> &#x0003C; 0.05; <xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 6</xref>; <xref ref-type="supplementary-material" rid="SM2">Supplementary Table 3</xref>). Notably, a total of 28, 51, and 19 differential metabolites presented the highest abundance in H, M, and S treatments, respectively (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
<fig id="F3" position="float">
<label>Figure 3</label>
<caption><p>The OPLS-DA plot and expression profile and VIP of metabolites between different comparison groups. <bold>(A&#x02013;C)</bold> The OPLS-DA plot of different comparison groups (the larger plot indicated the positive ion modes, and the smaller plot indicated the negative ion modes). <bold>(D&#x02013;F)</bold> The expression profile and VIP of metabolites of different comparison groups.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-10-1181942-g0003.tif"/>
</fig>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Details of 98 differential metabolites identified by LC-MS among the H, M, and S treatments.</p></caption> 
<table frame="box" rules="all">
<thead><tr style="background-color:#919497;color:#ffffff">
<th valign="top" align="left"><bold>Metabolite</bold></th>
<th valign="top" align="left"><bold>Formula</bold></th>
<th valign="top" align="center" colspan="3"><bold>H_vs_M</bold></th>
<th valign="top" align="center" colspan="3"><bold>H_vs_S</bold></th>
<th valign="top" align="center" colspan="3"><bold>S_vs_M</bold></th>
<th valign="top" align="center"><bold>H</bold></th>
<th valign="top" align="center"><bold>M</bold></th>
<th valign="top" align="center"><bold>S</bold></th>
</tr>
<tr style="background-color:#919497;color:#ffffff">
<td/>
<td/>
<td valign="top" align="center"><bold>VIP_PLS-DA</bold></td>
<td valign="top" align="center"><bold>FC(H/M)</bold></td>
<td valign="top" align="center"><italic><bold>P</bold></italic><bold>-value</bold></td>
<td valign="top" align="center"><bold>VIP_PLS-DA</bold></td>
<td valign="top" align="center"><bold>FC(H/S)</bold></td>
<td valign="top" align="center"><italic><bold>P</bold></italic><bold>-value</bold></td>
<td valign="top" align="center"><bold>VIP_PLS-DA</bold></td>
<td valign="top" align="center"><bold>FC(S/M)</bold></td>
<td valign="top" align="center"><italic><bold>P</bold></italic><bold>-value</bold></td>
<td/>
<td/>
<td/>
</tr> 
</thead>
<tbody>
<tr>
<td valign="top" align="left">12-Keto-tetrahydro-leukotriene B4</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>34</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.2881</td>
<td valign="top" align="center">0.9195</td>
<td valign="top" align="center">2.087E-14</td>
<td valign="top" align="center">0.6172</td>
<td valign="top" align="center">0.9814</td>
<td valign="top" align="center">2.679E-07</td>
<td valign="top" align="center">1.4599</td>
<td valign="top" align="center">0.9369</td>
<td valign="top" align="center">2.989E-14</td>
<td valign="top" align="center">6.44 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>7</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">6.56 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">2-Lysophosphatidylcholine (<xref ref-type="bibr" rid="B22">22</xref>)</td>
<td valign="top" align="left">C<sub>26</sub>H<sub>54</sub>NO<sub>7</sub>P</td>
<td valign="top" align="center">0.5838</td>
<td valign="top" align="center">0.9834</td>
<td valign="top" align="center">1.691E-07</td>
<td valign="top" align="center">0.5809</td>
<td valign="top" align="center">1.015</td>
<td valign="top" align="center">0.00000211</td>
<td valign="top" align="center">1.1207</td>
<td valign="top" align="center">0.9688</td>
<td valign="top" align="center">1.977E-10</td>
<td valign="top" align="center">7.22 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>7.34</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">7.12 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">2-Methoxyestradiol (<xref ref-type="bibr" rid="B23">23</xref>)</td>
<td valign="top" align="left">C<sub>19</sub>H<sub>26</sub>O<sub>3</sub></td>
<td valign="top" align="center">1.3934</td>
<td valign="top" align="center">0.8841</td>
<td valign="top" align="center">2.783E-09</td>
<td valign="top" align="center">0.7878</td>
<td valign="top" align="center">0.9609</td>
<td valign="top" align="center">0.0000174</td>
<td valign="top" align="center">1.4808</td>
<td valign="top" align="center">0.9201</td>
<td valign="top" align="center">2.552E-09</td>
<td valign="top" align="center">5.09 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.75</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.29 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">3-Methyl-2-oxovaleric acid (<xref ref-type="bibr" rid="B24">24</xref>)</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub>O<sub>3</sub></td>
<td valign="top" align="center">0.6357</td>
<td valign="top" align="center">1.024</td>
<td valign="top" align="center">0.000008318</td>
<td valign="top" align="center">1.3568</td>
<td valign="top" align="center">1.1</td>
<td valign="top" align="center">6.261E-13</td>
<td valign="top" align="center">1.4226</td>
<td valign="top" align="center">0.9309</td>
<td valign="top" align="center">9.081E-10</td>
<td valign="top" align="center"><bold>6.27</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.13 &#x000B1; 0.02</td>
<td valign="top" align="center">5.7 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">5,6-Dihydroxyprostaglandin F1a</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>36</sub>O<sub>7</sub></td>
<td valign="top" align="center">1.0454</td>
<td valign="top" align="center">0.9255</td>
<td valign="top" align="center">2.635E-07</td>
<td valign="top" align="center">1.4826</td>
<td valign="top" align="center">0.8747</td>
<td valign="top" align="center">1.044E-11</td>
<td valign="top" align="center">1.1795</td>
<td valign="top" align="center">1.0581</td>
<td valign="top" align="center">4.786E-07</td>
<td valign="top" align="center">4.76 &#x000B1; 0.02</td>
<td valign="top" align="center">5.14 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.44</bold> <bold>&#x000B1;0.01</bold></td>
</tr> <tr>
<td valign="top" align="left">Adenosine (<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>13</sub>N<sub>5</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.5127</td>
<td valign="top" align="center">1.134</td>
<td valign="top" align="center">2.726E-13</td>
<td valign="top" align="center">1.3645</td>
<td valign="top" align="center">1.0918</td>
<td valign="top" align="center">2.147E-12</td>
<td valign="top" align="center">1.107</td>
<td valign="top" align="center">1.0387</td>
<td valign="top" align="center">2.882E-07</td>
<td valign="top" align="center"><bold>6.71</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.92 &#x000B1; 0.01</td>
<td valign="top" align="center">6.14 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Aspartic acid (<xref ref-type="bibr" rid="B26">26</xref>)</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>7</sub>NO<sub>4</sub></td>
<td valign="top" align="center">1.0809</td>
<td valign="top" align="center">1.0817</td>
<td valign="top" align="center">5.692E-11</td>
<td valign="top" align="center">0.8941</td>
<td valign="top" align="center">1.0503</td>
<td valign="top" align="center">7.28E-08</td>
<td valign="top" align="center">0.808</td>
<td valign="top" align="center">1.0299</td>
<td valign="top" align="center">0.00001277</td>
<td valign="top" align="center"><bold>5.28</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">4.88 &#x000B1; 0.01</td>
<td valign="top" align="center">5.03 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Beta-alanine (<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>7</sub>NO<sub>2</sub></td>
<td valign="top" align="center">1.003</td>
<td valign="top" align="center">0.9474</td>
<td valign="top" align="center">9.56E-09</td>
<td valign="top" align="center">0.7627</td>
<td valign="top" align="center">0.9704</td>
<td valign="top" align="center">0.000003878</td>
<td valign="top" align="center">0.8361</td>
<td valign="top" align="center">0.9763</td>
<td valign="top" align="center">0.00001803</td>
<td valign="top" align="center">6.23 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.57</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.42 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Brassinolide (<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top" align="left">C<sub>28</sub>H<sub>48</sub>O<sub>6</sub></td>
<td valign="top" align="center">1.135</td>
<td valign="top" align="center">0.9405</td>
<td valign="top" align="center">1.08E-10</td>
<td valign="top" align="center">0.5866</td>
<td valign="top" align="center">0.9825</td>
<td valign="top" align="center">0.0003741</td>
<td valign="top" align="center">1.217</td>
<td valign="top" align="center">0.9573</td>
<td valign="top" align="center">0.000000167</td>
<td valign="top" align="center">6.95 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>7.39</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.08 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Bufalin (<xref ref-type="bibr" rid="B29">29</xref>)</td>
<td valign="top" align="left">C<sub>24</sub>H<sub>34</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.5954</td>
<td valign="top" align="center">0.8489</td>
<td valign="top" align="center">8.506E-09</td>
<td valign="top" align="center">0.6417</td>
<td valign="top" align="center">0.9666</td>
<td valign="top" align="center">0.009036</td>
<td valign="top" align="center">1.9781</td>
<td valign="top" align="center">0.8783</td>
<td valign="top" align="center">2.015E-08</td>
<td valign="top" align="center">5.03 &#x000B1; 0.04</td>
<td valign="top" align="center"><bold>5.92</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.2 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">Butyric acid (<xref ref-type="bibr" rid="B30">30</xref>)</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.4546</td>
<td valign="top" align="center">0.8526</td>
<td valign="top" align="center">1.137E-10</td>
<td valign="top" align="center">1.4403</td>
<td valign="top" align="center">0.8711</td>
<td valign="top" align="center">1.08E-10</td>
<td valign="top" align="center">0.6796</td>
<td valign="top" align="center">0.9788</td>
<td valign="top" align="center">0.002375</td>
<td valign="top" align="center">4.26 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>4.99</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">4.89 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Cephamycin C</td>
<td valign="top" align="left">C<sub>16</sub>H<sub>22</sub>N<sub>4</sub>O<sub>9</sub>S</td>
<td valign="top" align="center">0.6106</td>
<td valign="top" align="center">1.0277</td>
<td valign="top" align="center">0.01001</td>
<td valign="top" align="center">1.5627</td>
<td valign="top" align="center">1.1289</td>
<td valign="top" align="center">9.214E-07</td>
<td valign="top" align="center">1.7268</td>
<td valign="top" align="center">0.9104</td>
<td valign="top" align="center">0.00002892</td>
<td valign="top" align="center"><bold>6.74</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">6.56 &#x000B1; 0.05</td>
<td valign="top" align="center">5.97 &#x000B1; 0.07</td>
</tr> <tr>
<td valign="top" align="left">Cyclic AMP (<xref ref-type="bibr" rid="B31">31</xref>)</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>12</sub>N<sub>5</sub>O<sub>6</sub>P</td>
<td valign="top" align="center">1.2389</td>
<td valign="top" align="center">0.9085</td>
<td valign="top" align="center">2.538E-11</td>
<td valign="top" align="center">1.3459</td>
<td valign="top" align="center">0.9025</td>
<td valign="top" align="center">1.746E-12</td>
<td valign="top" align="center">0.3727</td>
<td valign="top" align="center">1.0066</td>
<td valign="top" align="center">0.004309</td>
<td valign="top" align="center">5.2 &#x000B1; 0.01</td>
<td valign="top" align="center">5.72 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.76</bold> <bold>&#x000B1;0</bold></td>
</tr> <tr>
<td valign="top" align="left">Cytidine (<xref ref-type="bibr" rid="B32">32</xref>)</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>13</sub>N<sub>3</sub>O<sub>5</sub></td>
<td valign="top" align="center">1.4123</td>
<td valign="top" align="center">0.89</td>
<td valign="top" align="center">1.256E-14</td>
<td valign="top" align="center">0.9494</td>
<td valign="top" align="center">0.9532</td>
<td valign="top" align="center">6.315E-11</td>
<td valign="top" align="center">1.5172</td>
<td valign="top" align="center">0.9337</td>
<td valign="top" align="center">3.443E-13</td>
<td valign="top" align="center">5.58 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.27</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.86 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Cytosine</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>5</sub>N<sub>3</sub>O</td>
<td valign="top" align="center">1.4064</td>
<td valign="top" align="center">0.8878</td>
<td valign="top" align="center">1.62E-14</td>
<td valign="top" align="center">0.9314</td>
<td valign="top" align="center">0.9537</td>
<td valign="top" align="center">1.881E-11</td>
<td valign="top" align="center">1.526</td>
<td valign="top" align="center">0.9309</td>
<td valign="top" align="center">4.702E-13</td>
<td valign="top" align="center">5.42 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.1</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.68 &#x000B1; 0</td>
</tr> <tr>
<td valign="top" align="left">D-(&#x0002B;)-Trehalose (<xref ref-type="bibr" rid="B33">33</xref>)</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>22</sub>O<sub>11</sub></td>
<td valign="top" align="center">0.5726</td>
<td valign="top" align="center">1.0144</td>
<td valign="top" align="center">0.000004033</td>
<td valign="top" align="center">1.181</td>
<td valign="top" align="center">1.0552</td>
<td valign="top" align="center">3.261E-10</td>
<td valign="top" align="center">1.2278</td>
<td valign="top" align="center">0.9613</td>
<td valign="top" align="center">5.058E-09</td>
<td valign="top" align="center"><bold>8.31</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">8.19 &#x000B1; 0.01</td>
<td valign="top" align="center">7.88 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Dehydroepiandrosterone Sulfate (<xref ref-type="bibr" rid="B34">34</xref>)</td>
<td valign="top" align="left">C<sub>19</sub>H<sub>28</sub>O<sub>5</sub>S</td>
<td valign="top" align="center">0.8396</td>
<td valign="top" align="center">0.9578</td>
<td valign="top" align="center">9.171E-08</td>
<td valign="top" align="center">1.1875</td>
<td valign="top" align="center">1.0849</td>
<td valign="top" align="center">1.665E-11</td>
<td valign="top" align="center">1.8122</td>
<td valign="top" align="center">0.8829</td>
<td valign="top" align="center">1.306E-11</td>
<td valign="top" align="center">5.59 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.83</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.15 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Deoxyuridine (<xref ref-type="bibr" rid="B35">35</xref>)</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>12</sub>N<sub>2</sub>O<sub>5</sub></td>
<td valign="top" align="center">2.0087</td>
<td valign="top" align="center">0.7362</td>
<td valign="top" align="center">5.484E-09</td>
<td valign="top" align="center">2.1873</td>
<td valign="top" align="center">0.7297</td>
<td valign="top" align="center">2.561E-09</td>
<td valign="top" align="center">0.3052</td>
<td valign="top" align="center">1.0089</td>
<td valign="top" align="center">0.2558</td>
<td valign="top" align="center">3.95 &#x000B1; 0.07</td>
<td valign="top" align="center">5.36 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.41</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">Diosgenin (<xref ref-type="bibr" rid="B36">36</xref>)</td>
<td valign="top" align="left">C<sub>27</sub>H<sub>42</sub>O<sub>3</sub></td>
<td valign="top" align="center">1.9033</td>
<td valign="top" align="center">0.8049</td>
<td valign="top" align="center">1.197E-12</td>
<td valign="top" align="center">1.9001</td>
<td valign="top" align="center">0.8255</td>
<td valign="top" align="center">4.764E-12</td>
<td valign="top" align="center">0.9343</td>
<td valign="top" align="center">0.975</td>
<td valign="top" align="center">7.904E-08</td>
<td valign="top" align="center">5.18 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>6.43</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.27 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Equilenin</td>
<td valign="top" align="left">C<sub>18</sub>H<sub>18</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.1279</td>
<td valign="top" align="center">0.9025</td>
<td valign="top" align="center">0.00001071</td>
<td valign="top" align="center">1.0862</td>
<td valign="top" align="center">1.1109</td>
<td valign="top" align="center">0.001193</td>
<td valign="top" align="center">2.1883</td>
<td valign="top" align="center">0.8124</td>
<td valign="top" align="center">0.000001781</td>
<td valign="top" align="center">4.37 &#x000B1; 0.05</td>
<td valign="top" align="center"><bold>4.84</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">3.93 &#x000B1; 0.09</td>
</tr> <tr>
<td valign="top" align="left">Ergocalciferol (<xref ref-type="bibr" rid="B37">37</xref>)</td>
<td valign="top" align="left">C<sub>28</sub>H<sub>44</sub>O</td>
<td valign="top" align="center">2.3201</td>
<td valign="top" align="center">0.7179</td>
<td valign="top" align="center">5.527E-12</td>
<td valign="top" align="center">2.4369</td>
<td valign="top" align="center">0.7253</td>
<td valign="top" align="center">8.566E-12</td>
<td valign="top" align="center">0.5711</td>
<td valign="top" align="center">0.9897</td>
<td valign="top" align="center">0.0002349</td>
<td valign="top" align="center">4.75 &#x000B1; 0.05</td>
<td valign="top" align="center"><bold>6.62</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.55 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Estrone (<xref ref-type="bibr" rid="B38">38</xref>)</td>
<td valign="top" align="left">C<sub>18</sub>H<sub>22</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.4975</td>
<td valign="top" align="center">0.8296</td>
<td valign="top" align="center">1.423E-07</td>
<td valign="top" align="center">1.7527</td>
<td valign="top" align="center">0.7979</td>
<td valign="top" align="center">1.351E-08</td>
<td valign="top" align="center">0.8834</td>
<td valign="top" align="center">1.0398</td>
<td valign="top" align="center">0.0001423</td>
<td valign="top" align="center">3.81 &#x000B1; 0.06</td>
<td valign="top" align="center">4.6 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>4.78</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">Ganosporeric acid A</td>
<td valign="top" align="left">C<sub>30</sub>H<sub>38</sub>O<sub>8</sub></td>
<td valign="top" align="center">0.8042</td>
<td valign="top" align="center">1.0653</td>
<td valign="top" align="center">0.02369</td>
<td valign="top" align="center">1.2672</td>
<td valign="top" align="center">1.1044</td>
<td valign="top" align="center">0.00004382</td>
<td valign="top" align="center">0.6269</td>
<td valign="top" align="center">0.9645</td>
<td valign="top" align="center">0.2246</td>
<td valign="top" align="center"><bold>5.65</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.3 &#x000B1; 0.13</td>
<td valign="top" align="center">5.11 &#x000B1; 0.07</td>
</tr> <tr>
<td valign="top" align="left">Geldanamycin (<xref ref-type="bibr" rid="B39">39</xref>)</td>
<td valign="top" align="left">C<sub>29</sub>H<sub>40</sub>N<sub>2</sub>O<sub>9</sub></td>
<td valign="top" align="center">1.2966</td>
<td valign="top" align="center">1.1057</td>
<td valign="top" align="center">1.713E-07</td>
<td valign="top" align="center">1.1005</td>
<td valign="top" align="center">1.0669</td>
<td valign="top" align="center">1.804E-07</td>
<td valign="top" align="center">0.868</td>
<td valign="top" align="center">1.0364</td>
<td valign="top" align="center">0.003196</td>
<td valign="top" align="center"><bold>6.14</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.55 &#x000B1; 0.04</td>
<td valign="top" align="center">5.75 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">Gluconic acid (<xref ref-type="bibr" rid="B40">40</xref>)</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>12</sub>O<sub>7</sub></td>
<td valign="top" align="center">0.8804</td>
<td valign="top" align="center">0.9614</td>
<td valign="top" align="center">2.142E-07</td>
<td valign="top" align="center">1.0331</td>
<td valign="top" align="center">0.9525</td>
<td valign="top" align="center">1.938E-08</td>
<td valign="top" align="center">0.454</td>
<td valign="top" align="center">1.0093</td>
<td valign="top" align="center">0.02008</td>
<td valign="top" align="center">6.74 &#x000B1; 0.01</td>
<td valign="top" align="center">7.01 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>7.08</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">GPCho (22:5/14:1)</td>
<td valign="top" align="left">C<sub>44</sub>H<sub>76</sub>NO<sub>8</sub>P</td>
<td valign="top" align="center">0.1699</td>
<td valign="top" align="center">0.996</td>
<td valign="top" align="center">0.2083</td>
<td valign="top" align="center">1.13</td>
<td valign="top" align="center">1.0669</td>
<td valign="top" align="center">0.000000014</td>
<td valign="top" align="center">1.5156</td>
<td valign="top" align="center">0.9336</td>
<td valign="top" align="center">2.189E-10</td>
<td valign="top" align="center">6.27 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.3</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.88 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Guanine (<xref ref-type="bibr" rid="B41">41</xref>)</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>5</sub>N<sub>5</sub>O</td>
<td valign="top" align="center">1.0697</td>
<td valign="top" align="center">0.9382</td>
<td valign="top" align="center">1.512E-12</td>
<td valign="top" align="center">0.3387</td>
<td valign="top" align="center">0.9929</td>
<td valign="top" align="center">0.001421</td>
<td valign="top" align="center">1.3975</td>
<td valign="top" align="center">0.9449</td>
<td valign="top" align="center">5.398E-12</td>
<td valign="top" align="center">6.03 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.43</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.08 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Guanosine (<xref ref-type="bibr" rid="B42">42</xref>)</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>13</sub>N<sub>5</sub>O<sub>5</sub></td>
<td valign="top" align="center">1.127</td>
<td valign="top" align="center">0.9375</td>
<td valign="top" align="center">2.015E-13</td>
<td valign="top" align="center">0.4325</td>
<td valign="top" align="center">0.9907</td>
<td valign="top" align="center">0.000006202</td>
<td valign="top" align="center">1.3355</td>
<td valign="top" align="center">0.9463</td>
<td valign="top" align="center">3.445E-13</td>
<td valign="top" align="center">6.46 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.9</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.53 &#x000B1; 0</td>
</tr> <tr>
<td valign="top" align="left">Ketoleucine (<xref ref-type="bibr" rid="B43">43</xref>)</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub>O<sub>3</sub></td>
<td valign="top" align="center">0.3546</td>
<td valign="top" align="center">1.0098</td>
<td valign="top" align="center">0.003071</td>
<td valign="top" align="center">0.9446</td>
<td valign="top" align="center">1.0514</td>
<td valign="top" align="center">1.795E-10</td>
<td valign="top" align="center">1.0261</td>
<td valign="top" align="center">0.9604</td>
<td valign="top" align="center">2.946E-08</td>
<td valign="top" align="center"><bold>5.69</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.63 &#x000B1; 0.01</td>
<td valign="top" align="center">5.41 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">L-(&#x0002B;)-Arginine (<xref ref-type="bibr" rid="B44">44</xref>)</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>14</sub>N<sub>4</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.5255</td>
<td valign="top" align="center">1.1735</td>
<td valign="top" align="center">1.83E-11</td>
<td valign="top" align="center">1.3891</td>
<td valign="top" align="center">1.1199</td>
<td valign="top" align="center">1.621E-11</td>
<td valign="top" align="center">1.0703</td>
<td valign="top" align="center">1.0479</td>
<td valign="top" align="center">0.00001412</td>
<td valign="top" align="center"><bold>5.47</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">4.66 &#x000B1; 0.02</td>
<td valign="top" align="center">4.88 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">L-Alanine (<xref ref-type="bibr" rid="B45">45</xref>)</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>7</sub>NO<sub>2</sub></td>
<td valign="top" align="center">0.3492</td>
<td valign="top" align="center">1.0076</td>
<td valign="top" align="center">0.00005126</td>
<td valign="top" align="center">0.946</td>
<td valign="top" align="center">1.0466</td>
<td valign="top" align="center">4.718E-11</td>
<td valign="top" align="center">1.113</td>
<td valign="top" align="center">0.9627</td>
<td valign="top" align="center">9.76E-11</td>
<td valign="top" align="center"><bold>6.09</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.04 &#x000B1; 0</td>
<td valign="top" align="center">5.81 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">L-Dopa (<xref ref-type="bibr" rid="B46">46</xref>)</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>11</sub>NO<sub>4</sub></td>
<td valign="top" align="center">1.2629</td>
<td valign="top" align="center">0.8902</td>
<td valign="top" align="center">1.162E-07</td>
<td valign="top" align="center">1.3286</td>
<td valign="top" align="center">0.8906</td>
<td valign="top" align="center">9.824E-09</td>
<td valign="top" align="center">0.0106</td>
<td valign="top" align="center">0.9996</td>
<td valign="top" align="center">0.9694</td>
<td valign="top" align="center">4.51 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>5.07</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.06 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Leukotriene B4 (<xref ref-type="bibr" rid="B47">47</xref>)</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>32</sub>O<sub>4</sub></td>
<td valign="top" align="center">0.2656</td>
<td valign="top" align="center">0.9877</td>
<td valign="top" align="center">0.2412</td>
<td valign="top" align="center">0.9371</td>
<td valign="top" align="center">0.9432</td>
<td valign="top" align="center">0.0001077</td>
<td valign="top" align="center">1.0264</td>
<td valign="top" align="center">1.0471</td>
<td valign="top" align="center">0.0000528</td>
<td valign="top" align="center">5.05 &#x000B1; 0.04</td>
<td valign="top" align="center">5.11 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.35</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">L-Glutamine (<xref ref-type="bibr" rid="B48">48</xref>)</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>10</sub>N<sub>2</sub>O<sub>3</sub></td>
<td valign="top" align="center">1.6822</td>
<td valign="top" align="center">1.1632</td>
<td valign="top" align="center">4.519E-17</td>
<td valign="top" align="center">1.933</td>
<td valign="top" align="center">1.1931</td>
<td valign="top" align="center">5.136E-19</td>
<td valign="top" align="center">0.9045</td>
<td valign="top" align="center">0.975</td>
<td valign="top" align="center">2.623E-09</td>
<td valign="top" align="center"><bold>6.97</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">5.99 &#x000B1; 0.01</td>
<td valign="top" align="center">5.84 &#x000B1; 0</td>
</tr> <tr>
<td valign="top" align="left">L-Phenylalanine (<xref ref-type="bibr" rid="B49">49</xref>)</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>11</sub>NO<sub>2</sub></td>
<td valign="top" align="center">1.7595</td>
<td valign="top" align="center">1.1779</td>
<td valign="top" align="center">4.929E-16</td>
<td valign="top" align="center">1.7053</td>
<td valign="top" align="center">1.1415</td>
<td valign="top" align="center">3.182E-15</td>
<td valign="top" align="center">1.02</td>
<td valign="top" align="center">1.0319</td>
<td valign="top" align="center">0.000000044</td>
<td valign="top" align="center"><bold>7.09</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.02 &#x000B1; 0.01</td>
<td valign="top" align="center">6.21 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">L-Proline (<xref ref-type="bibr" rid="B50">50</xref>)</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>9</sub>NO<sub>2</sub></td>
<td valign="top" align="center">0.8701</td>
<td valign="top" align="center">1.0392</td>
<td valign="top" align="center">2.109E-10</td>
<td valign="top" align="center">1.0631</td>
<td valign="top" align="center">1.0516</td>
<td valign="top" align="center">2.859E-10</td>
<td valign="top" align="center">0.6259</td>
<td valign="top" align="center">0.9881</td>
<td valign="top" align="center">0.0001529</td>
<td valign="top" align="center"><bold>7.01</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.74 &#x000B1; 0.01</td>
<td valign="top" align="center">6.66 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">L-Threonine (<xref ref-type="bibr" rid="B51">51</xref>)</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>9</sub>NO<sub>3</sub></td>
<td valign="top" align="center">0.9301</td>
<td valign="top" align="center">1.0537</td>
<td valign="top" align="center">5.07E-13</td>
<td valign="top" align="center">1.1132</td>
<td valign="top" align="center">1.0683</td>
<td valign="top" align="center">3.241E-12</td>
<td valign="top" align="center">0.6213</td>
<td valign="top" align="center">0.9863</td>
<td valign="top" align="center">0.0000209</td>
<td valign="top" align="center"><bold>5.87</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">5.57 &#x000B1; 0</td>
<td valign="top" align="center">5.49 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">L-Tryptophan (<xref ref-type="bibr" rid="B52">52</xref>)</td>
<td valign="top" align="left">C<sub>11</sub>H<sub>12</sub>N<sub>2</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.1645</td>
<td valign="top" align="center">1.0863</td>
<td valign="top" align="center">5.313E-13</td>
<td valign="top" align="center">1.1532</td>
<td valign="top" align="center">1.0767</td>
<td valign="top" align="center">7.973E-11</td>
<td valign="top" align="center">0.4141</td>
<td valign="top" align="center">1.009</td>
<td valign="top" align="center">0.005414</td>
<td valign="top" align="center"><bold>5.8</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.34 &#x000B1; 0.01</td>
<td valign="top" align="center">5.39 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">L-Tyrosine (<xref ref-type="bibr" rid="B53">53</xref>)</td>
<td valign="top" align="center">C9H11NO3</td>
<td valign="top" align="center">1.3773</td>
<td valign="top" align="center">1.126</td>
<td valign="top" align="center">1.63E-12</td>
<td valign="top" align="center">1.4919</td>
<td valign="top" align="center">1.1366</td>
<td valign="top" align="center">3.685E-10</td>
<td valign="top" align="center">0.32</td>
<td valign="top" align="center">0.9906</td>
<td valign="top" align="center">0.1615</td>
<td valign="top" align="center"><bold>5.77</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.12 &#x000B1; 0.01</td>
<td valign="top" align="center">5.07 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">LysoPC (15:0/0:0)</td>
<td valign="top" align="left">C<sub>23</sub>H<sub>48</sub>NO<sub>7</sub>P</td>
<td valign="top" align="center">0.5986</td>
<td valign="top" align="center">0.9786</td>
<td valign="top" align="center">3.555E-07</td>
<td valign="top" align="center">0.6493</td>
<td valign="top" align="center">1.0227</td>
<td valign="top" align="center">5.261E-08</td>
<td valign="top" align="center">1.1922</td>
<td valign="top" align="center">0.9569</td>
<td valign="top" align="center">1.796E-10</td>
<td valign="top" align="center">5.86 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.99</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.73 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">LysoPC (16:0/0:0)</td>
<td valign="top" align="left">C<sub>24</sub>H<sub>50</sub>NO<sub>7</sub>P</td>
<td valign="top" align="center">0.4884</td>
<td valign="top" align="center">0.9893</td>
<td valign="top" align="center">3.269E-07</td>
<td valign="top" align="center">0.5682</td>
<td valign="top" align="center">1.0129</td>
<td valign="top" align="center">3.924E-08</td>
<td valign="top" align="center">1.0086</td>
<td valign="top" align="center">0.9767</td>
<td valign="top" align="center">1.431E-10</td>
<td valign="top" align="center">7.85 &#x000B1; 0</td>
<td valign="top" align="center"><bold>7.93</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.75 &#x000B1; 0</td>
</tr> <tr>
<td valign="top" align="left">LysoPC [18:3 (6Z, 9Z, 12Z)/0:0]</td>
<td valign="top" align="left">C<sub>26</sub>H<sub>48</sub>NO<sub>7</sub>P</td>
<td valign="top" align="center">0.6051</td>
<td valign="top" align="center">1.017</td>
<td valign="top" align="center">0.000002267</td>
<td valign="top" align="center">1.1171</td>
<td valign="top" align="center">1.0499</td>
<td valign="top" align="center">7.677E-10</td>
<td valign="top" align="center">1.1627</td>
<td valign="top" align="center">0.9686</td>
<td valign="top" align="center">2.677E-09</td>
<td valign="top" align="center"><bold>8.01</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.88 &#x000B1; 0.01</td>
<td valign="top" align="center">7.63 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Malonic acid (<xref ref-type="bibr" rid="B54">54</xref>)</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>4</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.5618</td>
<td valign="top" align="center">1.171</td>
<td valign="top" align="center">8.85E-11</td>
<td valign="top" align="center">1.1371</td>
<td valign="top" align="center">1.0809</td>
<td valign="top" align="center">0.000007453</td>
<td valign="top" align="center">1.3505</td>
<td valign="top" align="center">1.0833</td>
<td valign="top" align="center">0.00001208</td>
<td valign="top" align="center"><bold>5.7</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">4.87 &#x000B1; 0.02</td>
<td valign="top" align="center">5.28 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">Mitomycin (<xref ref-type="bibr" rid="B55">55</xref>)</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>18</sub>N<sub>4</sub>O<sub>5</sub></td>
<td valign="top" align="center">0.2909</td>
<td valign="top" align="center">0.9915</td>
<td valign="top" align="center">0.03008</td>
<td valign="top" align="center">0.8314</td>
<td valign="top" align="center">1.0439</td>
<td valign="top" align="center">1.828E-07</td>
<td valign="top" align="center">1.1179</td>
<td valign="top" align="center">0.9498</td>
<td valign="top" align="center">1.123E-07</td>
<td valign="top" align="center">5.23 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.28</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.01 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Muramic acid</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>17</sub>NO<sub>7</sub></td>
<td valign="top" align="center">0.9483</td>
<td valign="top" align="center">0.9526</td>
<td valign="top" align="center">4.024E-10</td>
<td valign="top" align="center">0.373</td>
<td valign="top" align="center">1.0094</td>
<td valign="top" align="center">0.009346</td>
<td valign="top" align="center">1.4316</td>
<td valign="top" align="center">0.9437</td>
<td valign="top" align="center">9.616E-11</td>
<td valign="top" align="center">6.31 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.63</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">6.26 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">N-Acetylmannosamine (<xref ref-type="bibr" rid="B56">56</xref>)</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>15</sub>NO<sub>6</sub></td>
<td valign="top" align="center">0.7634</td>
<td valign="top" align="center">0.9631</td>
<td valign="top" align="center">5.354E-09</td>
<td valign="top" align="center">1.094</td>
<td valign="top" align="center">0.9365</td>
<td valign="top" align="center">5.816E-11</td>
<td valign="top" align="center">0.9232</td>
<td valign="top" align="center">1.0284</td>
<td valign="top" align="center">2.493E-07</td>
<td valign="top" align="center">5.36 &#x000B1; 0.01</td>
<td valign="top" align="center">5.56 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.72</bold> <bold>&#x000B1;0.01</bold></td>
</tr> <tr>
<td valign="top" align="left">N-Acetylmuramate</td>
<td valign="top" align="left">C<sub>11</sub>H<sub>19</sub>NO<sub>8</sub></td>
<td valign="top" align="center">1.296</td>
<td valign="top" align="center">0.8928</td>
<td valign="top" align="center">2.984E-09</td>
<td valign="top" align="center">0.4641</td>
<td valign="top" align="center">0.9802</td>
<td valign="top" align="center">0.02189</td>
<td valign="top" align="center">1.6295</td>
<td valign="top" align="center">0.9109</td>
<td valign="top" align="center">1.657E-08</td>
<td valign="top" align="center">4.9 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.49</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">N-Acetylneuraminic acid (<xref ref-type="bibr" rid="B57">57</xref>)</td>
<td valign="top" align="left">C<sub>11</sub>H<sub>19</sub>NO<sub>9</sub></td>
<td valign="top" align="center">0.7658</td>
<td valign="top" align="center">1.0304</td>
<td valign="top" align="center">9.489E-09</td>
<td valign="top" align="center">1.1511</td>
<td valign="top" align="center">1.0643</td>
<td valign="top" align="center">1.929E-09</td>
<td valign="top" align="center">0.9844</td>
<td valign="top" align="center">0.9682</td>
<td valign="top" align="center">0.000003255</td>
<td valign="top" align="center"><bold>6.87</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">6.67 &#x000B1; 0.01</td>
<td valign="top" align="center">6.46 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Nalidixic acid (<xref ref-type="bibr" rid="B58">58</xref>)</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>12</sub>N<sub>2</sub>O<sub>3</sub></td>
<td valign="top" align="center">1.1579</td>
<td valign="top" align="center">0.9087</td>
<td valign="top" align="center">2.029E-07</td>
<td valign="top" align="center">0.95</td>
<td valign="top" align="center">1.0694</td>
<td valign="top" align="center">0.0000251</td>
<td valign="top" align="center">1.9229</td>
<td valign="top" align="center">0.8497</td>
<td valign="top" align="center">2.164E-10</td>
<td valign="top" align="center">4.67 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.14</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">4.37 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Neomycin sulfate (<xref ref-type="bibr" rid="B59">59</xref>)</td>
<td valign="top" align="left">C<sub>23</sub>H<sub>46</sub>N<sub>6</sub>O<sub>13</sub></td>
<td valign="top" align="center">1.1703</td>
<td valign="top" align="center">0.9216</td>
<td valign="top" align="center">0.00001831</td>
<td valign="top" align="center">0.2307</td>
<td valign="top" align="center">0.9901</td>
<td valign="top" align="center">0.4427</td>
<td valign="top" align="center">1.56</td>
<td valign="top" align="center">0.9308</td>
<td valign="top" align="center">1.591E-07</td>
<td valign="top" align="center">6.02 &#x000B1; 0.07</td>
<td valign="top" align="center"><bold>6.53</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.08 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">Norepinephrine (<xref ref-type="bibr" rid="B60">60</xref>)</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>11</sub>NO<sub>3</sub></td>
<td valign="top" align="center">1.5133</td>
<td valign="top" align="center">0.8338</td>
<td valign="top" align="center">5.22E-09</td>
<td valign="top" align="center">1.2365</td>
<td valign="top" align="center">0.8893</td>
<td valign="top" align="center">7.604E-07</td>
<td valign="top" align="center">1.1774</td>
<td valign="top" align="center">0.9376</td>
<td valign="top" align="center">2.197E-07</td>
<td valign="top" align="center">3.95 &#x000B1; 0.04</td>
<td valign="top" align="center"><bold>4.74</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">4.44 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Ouabain (<xref ref-type="bibr" rid="B61">61</xref>)</td>
<td valign="top" align="left">C<sub>29</sub>H<sub>44</sub>O<sub>12</sub></td>
<td valign="top" align="center">1.4754</td>
<td valign="top" align="center">0.8844</td>
<td valign="top" align="center">3.256E-11</td>
<td valign="top" align="center">1.399</td>
<td valign="top" align="center">0.9031</td>
<td valign="top" align="center">1.709E-10</td>
<td valign="top" align="center">0.7647</td>
<td valign="top" align="center">0.9793</td>
<td valign="top" align="center">0.00004191</td>
<td valign="top" align="center">5.68 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.42</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.29 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Oxoglutaric acid</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>6</sub>O<sub>5</sub></td>
<td valign="top" align="center">1.4058</td>
<td valign="top" align="center">1.1129</td>
<td valign="top" align="center">1.327E-09</td>
<td valign="top" align="center">1.9174</td>
<td valign="top" align="center">1.2056</td>
<td valign="top" align="center">1.318E-11</td>
<td valign="top" align="center">1.4795</td>
<td valign="top" align="center">0.9231</td>
<td valign="top" align="center">2.862E-08</td>
<td valign="top" align="center"><bold>6.69</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">6.01 &#x000B1; 0.02</td>
<td valign="top" align="center">5.54 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [14:1 (9Z)/20:4 (8Z, 11Z, 14Z, 17Z)]</td>
<td valign="top" align="left">C<sub>37</sub>H<sub>63</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">0.9727</td>
<td valign="top" align="center">1.0565</td>
<td valign="top" align="center">1.243E-10</td>
<td valign="top" align="center">1.1752</td>
<td valign="top" align="center">1.0733</td>
<td valign="top" align="center">6.158E-10</td>
<td valign="top" align="center">0.6503</td>
<td valign="top" align="center">0.9844</td>
<td valign="top" align="center">0.0007635</td>
<td valign="top" align="center"><bold>6.17</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.84 &#x000B1; 0.01</td>
<td valign="top" align="center">5.75 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [16:1 (9Z)/22:4 (7Z, 10Z, 13Z, 16Z)]</td>
<td valign="top" align="left">C<sub>41</sub>H<sub>71</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">0.8219</td>
<td valign="top" align="center">0.9587</td>
<td valign="top" align="center">0.0001234</td>
<td valign="top" align="center">1.1136</td>
<td valign="top" align="center">0.9381</td>
<td valign="top" align="center">2.151E-07</td>
<td valign="top" align="center">0.7006</td>
<td valign="top" align="center">1.0219</td>
<td valign="top" align="center">0.005787</td>
<td valign="top" align="center">5.99 &#x000B1; 0.03</td>
<td valign="top" align="center">6.25 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>6.38</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">PA [18:3 (9Z, 12Z, 15Z)/18:3 (6Z, 9Z, 12Z)]</td>
<td valign="top" align="left">C<sub>39</sub>H<sub>65</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.2009</td>
<td valign="top" align="center">1.0922</td>
<td valign="top" align="center">0.000003993</td>
<td valign="top" align="center">0.943</td>
<td valign="top" align="center">1.0462</td>
<td valign="top" align="center">1.629E-07</td>
<td valign="top" align="center">1.0678</td>
<td valign="top" align="center">1.044</td>
<td valign="top" align="center">0.001126</td>
<td valign="top" align="center"><bold>6.25</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.73 &#x000B1; 0.06</td>
<td valign="top" align="center">5.98 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">PA [18:3 (9Z, 12Z, 15Z)/22:1 (13Z)]</td>
<td valign="top" align="left">C<sub>43</sub>H<sub>77</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.2323</td>
<td valign="top" align="center">0.9288</td>
<td valign="top" align="center">1.037E-09</td>
<td valign="top" align="center">0.7468</td>
<td valign="top" align="center">0.9736</td>
<td valign="top" align="center">0.00007617</td>
<td valign="top" align="center">1.3683</td>
<td valign="top" align="center">0.954</td>
<td valign="top" align="center">4.377E-09</td>
<td valign="top" align="center">6.93 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>7.46</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.12 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [18:4 (6Z, 9Z, 12Z, 15Z)/18:3 (6Z, 9Z, 12Z)]</td>
<td valign="top" align="left">C<sub>39</sub>H<sub>63</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.2772</td>
<td valign="top" align="center">1.0951</td>
<td valign="top" align="center">1.704E-09</td>
<td valign="top" align="center">1.1746</td>
<td valign="top" align="center">1.0687</td>
<td valign="top" align="center">2.409E-09</td>
<td valign="top" align="center">0.8253</td>
<td valign="top" align="center">1.0247</td>
<td valign="top" align="center">0.0009023</td>
<td valign="top" align="center"><bold>6.57</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6 &#x000B1; 0.03</td>
<td valign="top" align="center">6.14 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [20:0/20:4 (8Z, 11Z, 14Z, 17Z)]</td>
<td valign="top" align="left">C<sub>43</sub>H<sub>77</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.4539</td>
<td valign="top" align="center">0.8724</td>
<td valign="top" align="center">2.996E-08</td>
<td valign="top" align="center">1.7141</td>
<td valign="top" align="center">0.8499</td>
<td valign="top" align="center">7.768E-09</td>
<td valign="top" align="center">0.8744</td>
<td valign="top" align="center">1.0265</td>
<td valign="top" align="center">0.0001046</td>
<td valign="top" align="center">5.1 &#x000B1; 0.05</td>
<td valign="top" align="center">5.85 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">PA [20:1 (11Z)/22:5 (7Z, 10Z, 13Z, 16Z, 19Z)]</td>
<td valign="top" align="left">C<sub>45</sub>H<sub>77</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">0.9406</td>
<td valign="top" align="center">0.954</td>
<td valign="top" align="center">4.54E-08</td>
<td valign="top" align="center">0.2938</td>
<td valign="top" align="center">1.0081</td>
<td valign="top" align="center">0.09852</td>
<td valign="top" align="center">1.4076</td>
<td valign="top" align="center">0.9464</td>
<td valign="top" align="center">2.542E-08</td>
<td valign="top" align="center">6.5 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.81</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.44 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [20:3 (8Z, 11Z, 14Z)/22:2 (13Z, 16Z)]</td>
<td valign="top" align="left">C<sub>45</sub>H<sub>79</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.0355</td>
<td valign="top" align="center">0.9398</td>
<td valign="top" align="center">3.986E-09</td>
<td valign="top" align="center">0.5818</td>
<td valign="top" align="center">1.0228</td>
<td valign="top" align="center">0.001128</td>
<td valign="top" align="center">1.5376</td>
<td valign="top" align="center">0.9188</td>
<td valign="top" align="center">3.757E-09</td>
<td valign="top" align="center">5.74 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.11</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.62 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [20:4 (8Z, 11Z, 14Z, 17Z)/22:2 (13Z, 16Z)]</td>
<td valign="top" align="left">C<sub>45</sub>H<sub>77</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.0387</td>
<td valign="top" align="center">0.9434</td>
<td valign="top" align="center">3.526E-10</td>
<td valign="top" align="center">0.5468</td>
<td valign="top" align="center">1.0172</td>
<td valign="top" align="center">0.0001249</td>
<td valign="top" align="center">1.5058</td>
<td valign="top" align="center">0.9274</td>
<td valign="top" align="center">2.112E-10</td>
<td valign="top" align="center">6.14 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.51</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.04 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">PA [22:1 (13Z)/18:3 (9Z, 12Z, 15Z)]</td>
<td valign="top" align="left">C<sub>43</sub>H<sub>77</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.3305</td>
<td valign="top" align="center">0.9088</td>
<td valign="top" align="center">2.803E-10</td>
<td valign="top" align="center">0.7893</td>
<td valign="top" align="center">0.9672</td>
<td valign="top" align="center">0.000005046</td>
<td valign="top" align="center">1.3792</td>
<td valign="top" align="center">0.9397</td>
<td valign="top" align="center">1.305E-08</td>
<td valign="top" align="center">6.04 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.65</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">6.25 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">PA [22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/20:1 (11Z)]</td>
<td valign="top" align="left">C<sub>45</sub>H<sub>75</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">0.654</td>
<td valign="top" align="center">0.981</td>
<td valign="top" align="center">3.528E-07</td>
<td valign="top" align="center">0.7743</td>
<td valign="top" align="center">1.024</td>
<td valign="top" align="center">3.39E-08</td>
<td valign="top" align="center">1.3605</td>
<td valign="top" align="center">0.958</td>
<td valign="top" align="center">1.501E-09</td>
<td valign="top" align="center">7.9 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>8.05</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.71 &#x000B1; 0.01</td>
</tr> 
<tr>
<td valign="top" align="left">PA (8:0/12:0)</td>
<td valign="top" align="left">C<sub>23</sub>H<sub>45</sub>O<sub>8</sub>P</td>
<td valign="top" align="center">1.3973</td>
<td valign="top" align="center">0.8562</td>
<td valign="top" align="center">5.291E-08</td>
<td valign="top" align="center">0.4949</td>
<td valign="top" align="center">0.9821</td>
<td valign="top" align="center">1.267E-09</td>
<td valign="top" align="center">1.8206</td>
<td valign="top" align="center">0.8718</td>
<td valign="top" align="center">0.000000155</td>
<td valign="top" align="center">4.11 &#x000B1; 0</td>
<td valign="top" align="center"><bold>4.81</bold> <bold>&#x000B1;0.05</bold></td>
<td valign="top" align="center">4.19 &#x000B1; 0</td>
</tr> <tr>
<td valign="top" align="left">PC [14:0/22:5 (7Z, 10Z, 13Z, 16Z, 19Z)]</td>
<td valign="top" align="left">C<sub>44</sub>H<sub>78</sub>NO<sub>8</sub>P</td>
<td valign="top" align="center">0.5197</td>
<td valign="top" align="center">0.9815</td>
<td valign="top" align="center">0.01155</td>
<td valign="top" align="center">0.7204</td>
<td valign="top" align="center">1.0269</td>
<td valign="top" align="center">0.0006396</td>
<td valign="top" align="center">1.2483</td>
<td valign="top" align="center">0.9558</td>
<td valign="top" align="center">0.0001697</td>
<td valign="top" align="center">7.11 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>7.24</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">6.92 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">PC [14:0/22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)]</td>
<td valign="top" align="left">C<sub>44</sub>H<sub>76</sub>NO<sub>8</sub>P</td>
<td valign="top" align="center">0.5838</td>
<td valign="top" align="center">0.9812</td>
<td valign="top" align="center">0.00004699</td>
<td valign="top" align="center">0.8575</td>
<td valign="top" align="center">1.0349</td>
<td valign="top" align="center">2.131E-07</td>
<td valign="top" align="center">1.3986</td>
<td valign="top" align="center">0.9481</td>
<td valign="top" align="center">8.681E-09</td>
<td valign="top" align="center">6.79 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.92</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">6.56 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">PC [16:0/18:3 (9Z, 12Z, 15Z)]</td>
<td valign="top" align="left">C<sub>42</sub>H<sub>78</sub>NO<sub>8</sub>P</td>
<td valign="top" align="center">0.688</td>
<td valign="top" align="center">0.9739</td>
<td valign="top" align="center">0.0004022</td>
<td valign="top" align="center">0.4924</td>
<td valign="top" align="center">1.0123</td>
<td valign="top" align="center">0.0006259</td>
<td valign="top" align="center">1.1911</td>
<td valign="top" align="center">0.9621</td>
<td valign="top" align="center">0.00002371</td>
<td valign="top" align="center">7.16 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>7.35</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">7.07 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">PC [20:2 (11Z, 14Z)/14:0]</td>
<td valign="top" align="left">C<sub>42</sub>H<sub>80</sub>NO<sub>8</sub>P</td>
<td valign="top" align="center">1.572</td>
<td valign="top" align="center">0.8191</td>
<td valign="top" align="center">0.0008414</td>
<td valign="top" align="center">0.9179</td>
<td valign="top" align="center">0.9048</td>
<td valign="top" align="center">0.08466</td>
<td valign="top" align="center">1.3406</td>
<td valign="top" align="center">0.9054</td>
<td valign="top" align="center">0.03823</td>
<td valign="top" align="center">4.67 &#x000B1; 0.18</td>
<td valign="top" align="center"><bold>5.69</bold> <bold>&#x000B1;0.13</bold></td>
<td valign="top" align="center">5.16 &#x000B1; 0.19</td>
</tr> <tr>
<td valign="top" align="left">PE [22:4 (7Z, 10Z, 13Z, 16Z)/22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)]</td>
<td valign="top" align="left">C<sub>49</sub>H<sub>78</sub>NO<sub>8</sub>P</td>
<td valign="top" align="center">0.1155</td>
<td valign="top" align="center">1.0034</td>
<td valign="top" align="center">0.4959</td>
<td valign="top" align="center">0.893</td>
<td valign="top" align="center">0.9575</td>
<td valign="top" align="center">0.0001779</td>
<td valign="top" align="center">1.197</td>
<td valign="top" align="center">1.0479</td>
<td valign="top" align="center">0.0001871</td>
<td valign="top" align="center">6.18 &#x000B1; 0.02</td>
<td valign="top" align="center">6.16 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>6.45</bold> <bold>&#x000B1;0.04</bold></td>
</tr> <tr>
<td valign="top" align="left">PG (16:0/16:0)</td>
<td valign="top" align="left">C<sub>38</sub>H<sub>75</sub>O<sub>10</sub>P</td>
<td valign="top" align="center">0.7731</td>
<td valign="top" align="center">1.0509</td>
<td valign="top" align="center">0.005275</td>
<td valign="top" align="center">0.5675</td>
<td valign="top" align="center">0.967</td>
<td valign="top" align="center">0.08432</td>
<td valign="top" align="center">1.3345</td>
<td valign="top" align="center">1.0867</td>
<td valign="top" align="center">0.001889</td>
<td valign="top" align="center">5.6 &#x000B1; 0.04</td>
<td valign="top" align="center">5.33 &#x000B1; 0.06</td>
<td valign="top" align="center"><bold>5.79</bold> <bold>&#x000B1;0.09</bold></td>
</tr> <tr>
<td valign="top" align="left">PG [16:1 (9Z)/18:0]</td>
<td valign="top" align="left">C<sub>40</sub>H<sub>77</sub>O<sub>10</sub>P</td>
<td valign="top" align="center">1.8157</td>
<td valign="top" align="center">0.812</td>
<td valign="top" align="center">2.696E-10</td>
<td valign="top" align="center">1.2541</td>
<td valign="top" align="center">0.9084</td>
<td valign="top" align="center">0.000002623</td>
<td valign="top" align="center">1.8825</td>
<td valign="top" align="center">0.8939</td>
<td valign="top" align="center">2.97E-09</td>
<td valign="top" align="center">4.96 &#x000B1; 0.04</td>
<td valign="top" align="center"><bold>6.11</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.46 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">PG [18:2 (9Z, 12Z)/16:0]</td>
<td valign="top" align="left">C<sub>40</sub>H<sub>75</sub>O<sub>10</sub>P</td>
<td valign="top" align="center">1.4936</td>
<td valign="top" align="center">0.8873</td>
<td valign="top" align="center">9.34E-13</td>
<td valign="top" align="center">0.9864</td>
<td valign="top" align="center">0.9532</td>
<td valign="top" align="center">1.386E-08</td>
<td valign="top" align="center">1.6176</td>
<td valign="top" align="center">0.9309</td>
<td valign="top" align="center">3.772E-12</td>
<td valign="top" align="center">6.09 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.86</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.39 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">PG [22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/20:3 (8Z, 11Z, 14Z)]</td>
<td valign="top" align="left">C<sub>48</sub>H<sub>77</sub>O<sub>10</sub>P</td>
<td valign="top" align="center">1.2207</td>
<td valign="top" align="center">0.9237</td>
<td valign="top" align="center">3.143E-09</td>
<td valign="top" align="center">1.2945</td>
<td valign="top" align="center">0.9223</td>
<td valign="top" align="center">7.805E-10</td>
<td valign="top" align="center">0.0754</td>
<td valign="top" align="center">1.0015</td>
<td valign="top" align="center">0.7435</td>
<td valign="top" align="center">6.2 &#x000B1; 0.01</td>
<td valign="top" align="center">6.71 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.72</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">PGF2alpha (<xref ref-type="bibr" rid="B62">62</xref>)</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>34</sub>O<sub>5</sub></td>
<td valign="top" align="center">1.3698</td>
<td valign="top" align="center">0.9012</td>
<td valign="top" align="center">8.128E-15</td>
<td valign="top" align="center">0.8094</td>
<td valign="top" align="center">0.9659</td>
<td valign="top" align="center">1.035E-08</td>
<td valign="top" align="center">1.4399</td>
<td valign="top" align="center">0.933</td>
<td valign="top" align="center">1.408E-11</td>
<td valign="top" align="center">5.8 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.43</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Phenethylamine (<xref ref-type="bibr" rid="B63">63</xref>)</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>11</sub>N</td>
<td valign="top" align="center">1.5871</td>
<td valign="top" align="center">0.8151</td>
<td valign="top" align="center">3.489E-11</td>
<td valign="top" align="center">1.0509</td>
<td valign="top" align="center">0.9168</td>
<td valign="top" align="center">0.000001844</td>
<td valign="top" align="center">1.6969</td>
<td valign="top" align="center">0.8891</td>
<td valign="top" align="center">8.698E-10</td>
<td valign="top" align="center">3.86 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>4.73</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">4.21 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Pimelic acid</td>
<td valign="top" align="left">C<sub>7</sub>H<sub>12</sub>O<sub>4</sub></td>
<td valign="top" align="center">0.7622</td>
<td valign="top" align="center">1.0428</td>
<td valign="top" align="center">0.0001089</td>
<td valign="top" align="center">1.854</td>
<td valign="top" align="center">1.2503</td>
<td valign="top" align="center">8.601E-09</td>
<td valign="top" align="center">2.0098</td>
<td valign="top" align="center">0.834</td>
<td valign="top" align="center">8.096E-08</td>
<td valign="top" align="center"><bold>5.39</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.17 &#x000B1; 0.03</td>
<td valign="top" align="center">4.31 &#x000B1; 0.06</td>
</tr> <tr>
<td valign="top" align="left">Pregnenolone (<xref ref-type="bibr" rid="B64">64</xref>)</td>
<td valign="top" align="left">C<sub>21</sub>H<sub>32</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.0552</td>
<td valign="top" align="center">1.0677</td>
<td valign="top" align="center">6.302E-10</td>
<td valign="top" align="center">0.1636</td>
<td valign="top" align="center">1.0029</td>
<td valign="top" align="center">0.1285</td>
<td valign="top" align="center">1.4284</td>
<td valign="top" align="center">1.0646</td>
<td valign="top" align="center">1.846E-10</td>
<td valign="top" align="center"><bold>6.13</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.74 &#x000B1; 0.01</td>
<td valign="top" align="center">6.11 &#x000B1; 0</td>
</tr> <tr>
<td valign="top" align="left">Prostaglandin A1 (<xref ref-type="bibr" rid="B65">65</xref>)</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>32</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.2637</td>
<td valign="top" align="center">0.9188</td>
<td valign="top" align="center">1.22E-11</td>
<td valign="top" align="center">0.7696</td>
<td valign="top" align="center">0.9715</td>
<td valign="top" align="center">7.029E-08</td>
<td valign="top" align="center">1.4282</td>
<td valign="top" align="center">0.9457</td>
<td valign="top" align="center">2.111E-10</td>
<td valign="top" align="center">6.28 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.84</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.47 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Prostaglandin B1</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>32</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.1885</td>
<td valign="top" align="center">0.9278</td>
<td valign="top" align="center">1.268E-13</td>
<td valign="top" align="center">0.7168</td>
<td valign="top" align="center">0.9742</td>
<td valign="top" align="center">7.559E-08</td>
<td valign="top" align="center">1.2353</td>
<td valign="top" align="center">0.9523</td>
<td valign="top" align="center">7.229E-12</td>
<td valign="top" align="center">6.16 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.64</bold> <bold>&#x000B1;0</bold></td>
<td valign="top" align="center">6.33 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Prostaglandin B2</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>30</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.2817</td>
<td valign="top" align="center">0.8996</td>
<td valign="top" align="center">8.161E-11</td>
<td valign="top" align="center">0.9739</td>
<td valign="top" align="center">0.9438</td>
<td valign="top" align="center">2.87E-08</td>
<td valign="top" align="center">1.1156</td>
<td valign="top" align="center">0.9531</td>
<td valign="top" align="center">5.584E-09</td>
<td valign="top" align="center">5.03 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>5.59</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.33 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Prostaglandin D2 (<xref ref-type="bibr" rid="B66">66</xref>)</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>32</sub>O<sub>5</sub></td>
<td valign="top" align="center">0.4911</td>
<td valign="top" align="center">0.9827</td>
<td valign="top" align="center">0.001075</td>
<td valign="top" align="center">1.2123</td>
<td valign="top" align="center">0.9285</td>
<td valign="top" align="center">1.142E-10</td>
<td valign="top" align="center">1.3668</td>
<td valign="top" align="center">1.0584</td>
<td valign="top" align="center">4.715E-08</td>
<td valign="top" align="center">5.81 &#x000B1; 0.01</td>
<td valign="top" align="center">5.91 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.26</bold> <bold>&#x000B1;0.01</bold></td>
</tr> <tr>
<td valign="top" align="left">Prostaglandin E1 (<xref ref-type="bibr" rid="B67">67</xref>)</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>34</sub>O<sub>5</sub></td>
<td valign="top" align="center">1.4184</td>
<td valign="top" align="center">0.8865</td>
<td valign="top" align="center">1.212E-10</td>
<td valign="top" align="center">1.7529</td>
<td valign="top" align="center">0.8545</td>
<td valign="top" align="center">8.69E-12</td>
<td valign="top" align="center">1.119</td>
<td valign="top" align="center">1.0375</td>
<td valign="top" align="center">3.573E-08</td>
<td valign="top" align="center">5.47 &#x000B1; 0.02</td>
<td valign="top" align="center">6.17 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.4</bold> <bold>&#x000B1;0.01</bold></td>
</tr> <tr>
<td valign="top" align="left">Prostaglandin F1a</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>36</sub>O<sub>5</sub></td>
<td valign="top" align="center">1.8087</td>
<td valign="top" align="center">0.782</td>
<td valign="top" align="center">0.00000566</td>
<td valign="top" align="center">2.3332</td>
<td valign="top" align="center">0.718</td>
<td valign="top" align="center">2.109E-07</td>
<td valign="top" align="center">1.6338</td>
<td valign="top" align="center">1.0891</td>
<td valign="top" align="center">3.552E-08</td>
<td valign="top" align="center">4.32 &#x000B1; 0.14</td>
<td valign="top" align="center">5.52 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>6.01</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">Prostavasin (<xref ref-type="bibr" rid="B68">68</xref>)</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>34</sub>O<sub>5</sub></td>
<td valign="top" align="center">0.5111</td>
<td valign="top" align="center">0.9795</td>
<td valign="top" align="center">0.005108</td>
<td valign="top" align="center">1.2199</td>
<td valign="top" align="center">0.9264</td>
<td valign="top" align="center">3.93E-08</td>
<td valign="top" align="center">1.3557</td>
<td valign="top" align="center">1.0574</td>
<td valign="top" align="center">3.157E-08</td>
<td valign="top" align="center">5.79 &#x000B1; 0.03</td>
<td valign="top" align="center">5.91 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.25</bold> <bold>&#x000B1;0.01</bold></td>
</tr> <tr>
<td valign="top" align="left">PS [18:1 (9Z)/20:1 (11Z)]</td>
<td valign="top" align="left">C<sub>44</sub>H<sub>82</sub>NO<sub>10</sub>P</td>
<td valign="top" align="center">1.9575</td>
<td valign="top" align="center">0.7833</td>
<td valign="top" align="center">1.166E-07</td>
<td valign="top" align="center">1.5521</td>
<td valign="top" align="center">0.8621</td>
<td valign="top" align="center">0.00001838</td>
<td valign="top" align="center">1.7747</td>
<td valign="top" align="center">0.9085</td>
<td valign="top" align="center">8.99E-10</td>
<td valign="top" align="center">4.92 &#x000B1; 0.1</td>
<td valign="top" align="center"><bold>6.28</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.71 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Pyridoxine (<xref ref-type="bibr" rid="B69">69</xref>)</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>11</sub>NO<sub>3</sub></td>
<td valign="top" align="center">0.5143</td>
<td valign="top" align="center">1.0187</td>
<td valign="top" align="center">0.0006751</td>
<td valign="top" align="center">0.5471</td>
<td valign="top" align="center">0.9812</td>
<td valign="top" align="center">0.002176</td>
<td valign="top" align="center">1.0699</td>
<td valign="top" align="center">1.0383</td>
<td valign="top" align="center">0.00001543</td>
<td valign="top" align="center">5.93 &#x000B1; 0.02</td>
<td valign="top" align="center">5.82 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>6.05</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">Riboflavin (<xref ref-type="bibr" rid="B70">70</xref>)</td>
<td valign="top" align="left">C<sub>17</sub>H<sub>20</sub>N<sub>4</sub>O<sub>6</sub></td>
<td valign="top" align="center">0.9617</td>
<td valign="top" align="center">0.9443</td>
<td valign="top" align="center">3.59E-10</td>
<td valign="top" align="center">0.5364</td>
<td valign="top" align="center">0.9834</td>
<td valign="top" align="center">0.000004509</td>
<td valign="top" align="center">1.1174</td>
<td valign="top" align="center">0.9602</td>
<td valign="top" align="center">3.432E-08</td>
<td valign="top" align="center">5.46 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.78</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">5.55 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">S-adenosyl-L-methioninamine</td>
<td valign="top" align="left">C<sub>14</sub>H<sub>24</sub>N<sub>6</sub>O<sub>3</sub>S&#x0002B;2</td>
<td valign="top" align="center">2.0755</td>
<td valign="top" align="center">0.7605</td>
<td valign="top" align="center">1.751E-11</td>
<td valign="top" align="center">2.1985</td>
<td valign="top" align="center">0.7568</td>
<td valign="top" align="center">2.559E-12</td>
<td valign="top" align="center">0.1811</td>
<td valign="top" align="center">1.0049</td>
<td valign="top" align="center">0.4756</td>
<td valign="top" align="center">4.66 &#x000B1; 0.03</td>
<td valign="top" align="center">6.13 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>6.16</bold> <bold>&#x000B1;0.02</bold></td>
</tr> <tr>
<td valign="top" align="left">S-Adenosylmethionine (<xref ref-type="bibr" rid="B71">71</xref>)</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>23</sub>N<sub>6</sub>O<sub>5</sub>S&#x0002B;</td>
<td valign="top" align="center">2.4903</td>
<td valign="top" align="center">0.6324</td>
<td valign="top" align="center">2.639E-09</td>
<td valign="top" align="center">1.5273</td>
<td valign="top" align="center">0.822</td>
<td valign="top" align="center">0.00004823</td>
<td valign="top" align="center">2.531</td>
<td valign="top" align="center">0.7693</td>
<td valign="top" align="center">2.298E-10</td>
<td valign="top" align="center">3.66 &#x000B1; 0.11</td>
<td valign="top" align="center"><bold>5.79</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">4.45 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">Serotonin (<xref ref-type="bibr" rid="B72">72</xref>)</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>12</sub>N<sub>2</sub>O</td>
<td valign="top" align="center">1.4567</td>
<td valign="top" align="center">1.1507</td>
<td valign="top" align="center">5.291E-13</td>
<td valign="top" align="center">1.3166</td>
<td valign="top" align="center">1.1032</td>
<td valign="top" align="center">1.48E-12</td>
<td valign="top" align="center">1.0708</td>
<td valign="top" align="center">1.0431</td>
<td valign="top" align="center">8.973E-09</td>
<td valign="top" align="center"><bold>5.61</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">4.88 &#x000B1; 0.01</td>
<td valign="top" align="center">5.09 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Suberic acid</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>14</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.0863</td>
<td valign="top" align="center">0.9267</td>
<td valign="top" align="center">1.068E-09</td>
<td valign="top" align="center">1.2671</td>
<td valign="top" align="center">0.9111</td>
<td valign="top" align="center">3.023E-11</td>
<td valign="top" align="center">0.6243</td>
<td valign="top" align="center">1.0171</td>
<td valign="top" align="center">0.0003453</td>
<td valign="top" align="center">5.1 &#x000B1; 0.01</td>
<td valign="top" align="center">5.51 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>5.6</bold> <bold>&#x000B1;0.01</bold></td>
</tr> <tr>
<td valign="top" align="left">Sucrose (<xref ref-type="bibr" rid="B73">73</xref>)</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>22</sub>O<sub>11</sub></td>
<td valign="top" align="center">0.8143</td>
<td valign="top" align="center">1.0305</td>
<td valign="top" align="center">0.000002013</td>
<td valign="top" align="center">1.1728</td>
<td valign="top" align="center">1.0573</td>
<td valign="top" align="center">9.601E-09</td>
<td valign="top" align="center">0.9264</td>
<td valign="top" align="center">0.9747</td>
<td valign="top" align="center">0.00004525</td>
<td valign="top" align="center"><bold>7.97</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.74 &#x000B1; 0.02</td>
<td valign="top" align="center">7.54 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Thromboxane B2</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>34</sub>O<sub>6</sub></td>
<td valign="top" align="center">1.1626</td>
<td valign="top" align="center">0.9171</td>
<td valign="top" align="center">2.354E-09</td>
<td valign="top" align="center">1.0983</td>
<td valign="top" align="center">0.9321</td>
<td valign="top" align="center">3.497E-12</td>
<td valign="top" align="center">0.5755</td>
<td valign="top" align="center">0.9839</td>
<td valign="top" align="center">0.004316</td>
<td valign="top" align="center">5.14 &#x000B1; 0</td>
<td valign="top" align="center"><bold>5.6</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.51 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Thyrotropin-releasing factor (<xref ref-type="bibr" rid="B74">74</xref>)</td>
<td valign="top" align="left">C<sub>16</sub>H<sub>22</sub>N<sub>6</sub>O<sub>4</sub></td>
<td valign="top" align="center">1.5535</td>
<td valign="top" align="center">0.8584</td>
<td valign="top" align="center">5.68E-10</td>
<td valign="top" align="center">1.1585</td>
<td valign="top" align="center">0.9216</td>
<td valign="top" align="center">1.523E-07</td>
<td valign="top" align="center">1.3764</td>
<td valign="top" align="center">0.9314</td>
<td valign="top" align="center">1.753E-08</td>
<td valign="top" align="center">5.01 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.83</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.43 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Trehalose (<xref ref-type="bibr" rid="B75">75</xref>)</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>22</sub>O<sub>11</sub></td>
<td valign="top" align="center">0.5691</td>
<td valign="top" align="center">1.0165</td>
<td valign="top" align="center">0.00005649</td>
<td valign="top" align="center">1.0235</td>
<td valign="top" align="center">1.0443</td>
<td valign="top" align="center">5.364E-08</td>
<td valign="top" align="center">1.016</td>
<td valign="top" align="center">0.9734</td>
<td valign="top" align="center">0.00001035</td>
<td valign="top" align="center"><bold>7.64</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.51 &#x000B1; 0.01</td>
<td valign="top" align="center">7.31 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">Uracil (<xref ref-type="bibr" rid="B76">76</xref>)</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub></td>
<td valign="top" align="center">1.0516</td>
<td valign="top" align="center">0.9392</td>
<td valign="top" align="center">8.617E-13</td>
<td valign="top" align="center">0.6838</td>
<td valign="top" align="center">0.9761</td>
<td valign="top" align="center">4.514E-08</td>
<td valign="top" align="center">1.1451</td>
<td valign="top" align="center">0.9622</td>
<td valign="top" align="center">4.122E-10</td>
<td valign="top" align="center">5.92 &#x000B1; 0.01</td>
<td valign="top" align="center"><bold>6.3</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">6.07 &#x000B1; 0.01</td>
</tr> <tr>
<td valign="top" align="left">Uridine (<xref ref-type="bibr" rid="B77">77</xref>)</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>12</sub>N<sub>2</sub>O<sub>6</sub></td>
<td valign="top" align="center">1.0592</td>
<td valign="top" align="center">0.9482</td>
<td valign="top" align="center">1.785E-10</td>
<td valign="top" align="center">0.4745</td>
<td valign="top" align="center">0.9895</td>
<td valign="top" align="center">0.000007563</td>
<td valign="top" align="center">1.2138</td>
<td valign="top" align="center">0.9582</td>
<td valign="top" align="center">3.083E-09</td>
<td valign="top" align="center">7 &#x000B1; 0</td>
<td valign="top" align="center"><bold>7.39</bold> <bold>&#x000B1;0.01</bold></td>
<td valign="top" align="center">7.08 &#x000B1; 0.01</td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>The bold values indicated the highest abundance.</p>
</table-wrap-foot>
</table-wrap>
<sec>
<title>3.3.1. Saccharides</title>
<p>As shown in <xref ref-type="fig" rid="F4">Figures 4A</xref>&#x02013;<xref ref-type="fig" rid="F4">C</xref>, the abundances of sucrose, trehalose, and D-(&#x0002B;)-trehalose were ranked as H&#x0003E;M&#x0003E;S, suggesting that the H and M treatments favored the formation and accumulation of these three substances in comparison with the S treatment. Meanwhile, the abundances of gluconic acid and N-acetylmannosamine under the three treatments were ranked as S&#x0003E;M&#x0003E;H, indicating that the S and M treatments were more conducive to the formation and accumulation of these two substances in comparison to the H treatment (<xref ref-type="fig" rid="F4">Figures 4D</xref>, <xref ref-type="fig" rid="F4">E</xref>).</p>
<fig id="F4" position="float">
<label>Figure 4</label>
<caption><p>The relative abundance of the differential saccharides among the H, M, and S treatments. <bold>(A&#x02013;E)</bold> The abundances of Sucrose, Trehalose, D-(&#x0002B;)-Trehalose, NAcetylmannosamine, and Gluconic Acid among the three treatments, respectively. The treatments containing the same letters indicated no significant differences (<italic>p</italic> &#x0003E; 0.05), while the treatments containing different letters indicated significant differences (<italic>p</italic> &#x0003C; 0.05).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-10-1181942-g0004.tif"/>
</fig></sec>
<sec>
<title>3.3.2. Amino acids</title>
<p>Amino acids are important nutrients for <italic>P. palustre</italic>. Here, we identified 11 differential amino acids, including L-dopa, L-proline, L-alanine, L-glutamine, L-phenylalanine, L-threonine, L-(&#x0002B;)-arginine, beta-alanine, L-tryptophan, L-tyrosine, and aspartic Acid. As shown in <xref ref-type="fig" rid="F5">Figure 5</xref>, the relative abundances of L-dopa and L-alanine in the H treatment were significantly lower than those of the M and S treatments, whereas the relative abundances of the other nine amino acids in the H treatment were dramatically higher than those of the M and S treatments. This suggested that the H treatment could promote the amino acid content of <italic>P. palustre</italic>. In particular, aspartic acid and glutamic acid are delicious amino acids, and alanine, serine, and glycine are sweet amino acids in <italic>P. palustre</italic> (<xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B78">78</xref>). In our investigation, the abundances of aspartic acid and L-alanine in the H treatment were significantly increased compared with the M and S treatments, while the beta-alanine presented the lowest abundance in the H treatment.</p>
<fig id="F5" position="float">
<label>Figure 5</label>
<caption><p>The relative abundance of the differential amino acids among the H, M, and S treatments. <bold>(A&#x02013;K)</bold> The abundances of Aspartic Acid, L-(&#x0002B;)-Arginine, L-Phenylalanine, LProline, L-Threonine, L-Glutamine, L-Tryptophan, L-Tyrosine, L-Alanine, L-Dopa, and Beta-Alanine among the three treatments, respectively. The treatments containing the same letters indicated no significant differences (<italic>p</italic> &#x0003E; 0.05), while the treatments containing different letters indicated significant differences (<italic>p</italic> &#x0003C; 0.05).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-10-1181942-g0005.tif"/>
</fig></sec></sec>
<sec>
<title>3.4. Volatile compounds analysis based on HS-GC-MS</title>
<p>In this study, we also used the HS-GC-MS technique to investigate the effects of different processing treatments on the volatile components of <italic>P. palustre</italic>. The results showed that a total of 242 metabolites were identified by HS-GC-MS. The analysis of correlation, PCA, Venn, and PLS-DA indicated that the data were reliable and available (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 7</xref>). Based on these metabolites, in total, 55 volatile substances were identified in HMDB, including organic oxygen compounds (17, 30.91%), lipids and lipid-like molecules (15, 27.27%), organic acids and derivatives (8, 14.55%), organoheterocyclic compounds (8, 14.55%), benzenoids (6, 10.91%), and hydrocarbons (1, 1.82%; <xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 8A</xref>; <xref ref-type="supplementary-material" rid="SM2">Supplementary Table 4</xref>). Among these, carbonyl compounds, fatty acids and conjugates, and pyrazines accounted for almost half of the volatile substances (27/55; <xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 8B</xref>).</p></sec>
<sec>
<title>3.5. Differential volatile substances among the different treatments</title>
<p>The different groups could be better distinguished by OPLS-DA analysis (<xref ref-type="fig" rid="F6">Figures 6A</xref>&#x02013;<xref ref-type="fig" rid="F6">C</xref>). All the identified volatile substances were employed for screening differential metabolites according to the VIP &#x0003E; 1 and <italic>p</italic> &#x0003C; 0.05, and the results of the three comparison groups are shown in <xref ref-type="fig" rid="F6">Figures 6D</xref>&#x02013;<xref ref-type="fig" rid="F6">F</xref>. The results showed that a total of 109 differential volatile substances were detected among the H, M, and S treatments (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 8C</xref>). Of these, there were 70 (23 upregulated and 47 downregulated), 74 (20 upregulated and 54 downregulated), and 44 (22 upregulated and 22 downregulated) differential volatile substances in H vs. M, H vs. S, and S vs. M treatments, respectively (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figures 8D</xref>&#x02013;<xref ref-type="supplementary-material" rid="SM1">F</xref>). Based on these differential volatile substances, we identified 27 differential volatile substances in HMDB (<xref ref-type="table" rid="T2">Table 2</xref>), including lipids and lipid-like molecules (10, 37.04%), organic oxygen compounds (7, 25.93%), organoheterocyclic compounds (5, 18.52%), benzenoids (2, 7.41%), organic acids and derivatives (2, 7.41%), and hydrocarbons (1, 3.7%) under superclass classification or carbonyl compounds (6, 22.22%), fatty acids and conjugates (6, 22.22%), pyrazines (4, 14.81%), unknown (3, 11.11%), fatty alcohols (2, 7.41%), monoterpenoids (2, 7.41%), benzoic acids and derivatives (1, 3.7%), carboxylic acid derivatives (1, 3.7%), carboxylic acids (1, 3.7%), and olefins (1, 3.7%), under subclass classification (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 9</xref>; <xref ref-type="supplementary-material" rid="SM2">Supplementary Table 5</xref>). Of these, there were 18, 17, and 11 differential volatile substances in H vs. M, H vs. S, and S vs. M comparisons, respectively. In addition, among the three treatments, there were 11, 9, and 7 differential volatile substances showing the highest abundance in the H, M, and S treatments, respectively (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
<fig id="F6" position="float">
<label>Figure 6</label>
<caption><p>The OPLS-DA plot and expression profile and VIP of volatile substances. <bold>(A&#x02013;C)</bold> The OPLSDA plot of different comparison groups. <bold>(D&#x02013;F)</bold> The expression profile and VIP of volatile substances of different comparison groups.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-10-1181942-g0006.tif"/>
</fig>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Details of 27 differential metabolites identified by HS-GC-MS among the H, M, and S treatments.</p></caption> 
<table frame="box" rules="all">
<thead><tr style="background-color:#919497;color:#ffffff">
<th valign="top" align="left"><bold>Metabolite</bold></th>
<th valign="top" align="center"><bold>Quant mass</bold></th>
<th valign="top" align="center"><bold>Formula</bold></th>
<th valign="top" align="center"><bold>Retention time</bold></th>
<th valign="top" align="center"><bold>RSD</bold></th>
<th valign="top" align="center"><bold>Score</bold></th>
<th valign="top" align="center"><bold>CAS ID</bold></th>
<th valign="top" align="center"><bold>H</bold></th>
<th valign="top" align="center"><bold>M</bold></th>
<th valign="top" align="center"><bold>S</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">3-methylcyclopentene</td>
<td valign="top" align="center">67</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub></td>
<td valign="top" align="center">1.569</td>
<td valign="top" align="center">0.070507784</td>
<td valign="top" align="center">84.7829959</td>
<td valign="top" align="center">1120-62-3</td>
<td valign="top" align="center">4.17 &#x000B1; 0.02</td>
<td valign="top" align="center"><bold>4.79</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">4.72 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">2-methylpropanal</td>
<td valign="top" align="center">72</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>O</td>
<td valign="top" align="center">1.625</td>
<td valign="top" align="center">0.068787109</td>
<td valign="top" align="center">96.96030378</td>
<td valign="top" align="center">78-84-2</td>
<td valign="top" align="center"><bold>6.46</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">6.27 &#x000B1; 0.02</td>
<td valign="top" align="center">6.35 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">Acetohydrazide</td>
<td valign="top" align="center">74</td>
<td valign="top" align="left">C<sub>2</sub>H<sub>6</sub>N<sub>2</sub>O</td>
<td valign="top" align="center">1.694</td>
<td valign="top" align="center">0.0762885</td>
<td valign="top" align="center">95.19998129</td>
<td valign="top" align="center">7467-32-5</td>
<td valign="top" align="center">6.01 &#x000B1; 0.02</td>
<td valign="top" align="center">5.86 &#x000B1; 0.04</td>
<td valign="top" align="center"><bold>6.09</bold> <bold>&#x000B1;0.03</bold></td>
</tr> <tr>
<td valign="top" align="left">Butan-2-one</td>
<td valign="top" align="center">72.1</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>O</td>
<td valign="top" align="center">1.933</td>
<td valign="top" align="center">0.07628602</td>
<td valign="top" align="center">84.38764977</td>
<td valign="top" align="center">78-93-3</td>
<td valign="top" align="center">4.63 &#x000B1; 0.02</td>
<td valign="top" align="center">4.67 &#x000B1; 0.09</td>
<td valign="top" align="center"><bold>4.87</bold> <bold>&#x000B1;0.05</bold></td>
</tr> <tr>
<td valign="top" align="left">2-ethoxyacetic acid</td>
<td valign="top" align="center">60</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>O<sub>3</sub></td>
<td valign="top" align="center">2.049</td>
<td valign="top" align="center">0.058061107</td>
<td valign="top" align="center">63.28450641</td>
<td valign="top" align="center">627-03-2</td>
<td valign="top" align="center"><bold>3.64</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">3.42 &#x000B1; 0.03</td>
<td valign="top" align="center">3.56 &#x000B1; 0.03</td>
</tr> <tr>
<td valign="top" align="left">2-methylbutanal (<xref ref-type="bibr" rid="B79">79</xref>)</td>
<td valign="top" align="center">57</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>10</sub>O</td>
<td valign="top" align="center">2.211</td>
<td valign="top" align="center">0.074138387</td>
<td valign="top" align="center">97.24812074</td>
<td valign="top" align="center">57456-98-1;96-17-3</td>
<td valign="top" align="center"><bold>6.58</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">6.28 &#x000B1; 0.04</td>
<td valign="top" align="center">6.33 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">2-ethyl-5-methylfuran</td>
<td valign="top" align="center">95</td>
<td valign="top" align="left">C<sub>7</sub>H<sub>10</sub>O</td>
<td valign="top" align="center">3.597</td>
<td valign="top" align="center">0.130583098</td>
<td valign="top" align="center">50.40601524</td>
<td valign="top" align="center">1703-52-2</td>
<td valign="top" align="center">4.05 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>4.49</bold> <bold>&#x000B1;0.14</bold></td>
<td valign="top" align="center">4.16 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">Terpinolene (<xref ref-type="bibr" rid="B80">80</xref>)</td>
<td valign="top" align="center">93</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>16</sub></td>
<td valign="top" align="center">4.036</td>
<td valign="top" align="center">0.082818836</td>
<td valign="top" align="center">53.3918106</td>
<td valign="top" align="center">586-62-9</td>
<td valign="top" align="center"><bold>4.02</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">3.75 &#x000B1; 0.1</td>
<td valign="top" align="center">3.88 &#x000B1; 0.06</td>
</tr> <tr>
<td valign="top" align="left">Hexanal (<xref ref-type="bibr" rid="B81">81</xref>)</td>
<td valign="top" align="center">56</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>12</sub>O</td>
<td valign="top" align="center">4.418</td>
<td valign="top" align="center">0.0853182</td>
<td valign="top" align="center">92.3798746</td>
<td valign="top" align="center">66-25-1</td>
<td valign="top" align="center">4.94 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.17</bold> <bold>&#x000B1;0.09</bold></td>
<td valign="top" align="center">5.14 &#x000B1; 0.07</td>
</tr> <tr>
<td valign="top" align="left">(3E)-4,8-dimethylnona-1,3,7-triene</td>
<td valign="top" align="center">69</td>
<td valign="top" align="left">C<sub>11</sub>H<sub>18</sub></td>
<td valign="top" align="center">8.618</td>
<td valign="top" align="center">0.060793879</td>
<td valign="top" align="center">73.47215285</td>
<td valign="top" align="center">19945-61-0</td>
<td valign="top" align="center"><bold>4.91</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">4.15 &#x000B1; 0.24</td>
<td valign="top" align="center">4.68 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">2-Methylpyrazine</td>
<td valign="top" align="center">94</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>6</sub>N<sub>2</sub></td>
<td valign="top" align="center">8.877</td>
<td valign="top" align="center">0.057517825</td>
<td valign="top" align="center">95.00709536</td>
<td valign="top" align="center">109-08-0</td>
<td valign="top" align="center"><bold>5.92</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.59 &#x000B1; 0.02</td>
<td valign="top" align="center">5.67 &#x000B1; 0.02</td>
</tr> <tr>
<td valign="top" align="left">2,3-Pentanedione</td>
<td valign="top" align="center">57</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>8</sub>O<sub>2</sub></td>
<td valign="top" align="center">9.369</td>
<td valign="top" align="center">0.015632225</td>
<td valign="top" align="center">57.40072131</td>
<td valign="top" align="center">600-14-6</td>
<td valign="top" align="center">3.99 &#x000B1; 0.06</td>
<td valign="top" align="center"><bold>4.18</bold> <bold>&#x000B1;0.05</bold></td>
<td valign="top" align="center">3.99 &#x000B1; 0.06</td>
</tr> <tr>
<td valign="top" align="left">2-methylpentanoic acid</td>
<td valign="top" align="center">98.9</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>12</sub>O<sub>2</sub></td>
<td valign="top" align="center">9.709</td>
<td valign="top" align="center">0.063366089</td>
<td valign="top" align="center">83.01372596</td>
<td valign="top" align="center">22160-39-0;97-61-0</td>
<td valign="top" align="center">4.27 &#x000B1; 0.03</td>
<td valign="top" align="center">4.21 &#x000B1; 0.49</td>
<td valign="top" align="center"><bold>4.65</bold> <bold>&#x000B1;0.04</bold></td>
</tr> <tr>
<td valign="top" align="left">2,5-dimethylpyrazine (<xref ref-type="bibr" rid="B82">82</xref>)</td>
<td valign="top" align="center">108</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>8</sub>N<sub>2</sub></td>
<td valign="top" align="center">10.203</td>
<td valign="top" align="center">0.071420374</td>
<td valign="top" align="center">59.35896515</td>
<td valign="top" align="center">123-32-0</td>
<td valign="top" align="center"><bold>5.14</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">4.84 &#x000B1; 0.07</td>
<td valign="top" align="center">4.82 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">2-ethylpyrazine (<xref ref-type="bibr" rid="B83">83</xref>)</td>
<td valign="top" align="center">108</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>8</sub>N<sub>2</sub></td>
<td valign="top" align="center">10.356</td>
<td valign="top" align="center">0.058623043</td>
<td valign="top" align="center">92.05534271</td>
<td valign="top" align="center">13925-00-3</td>
<td valign="top" align="center"><bold>5.4</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">5 &#x000B1; 0.06</td>
<td valign="top" align="center">5.08 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">Oct-1-en-3-ol</td>
<td valign="top" align="center">57.2</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>16</sub>O</td>
<td valign="top" align="center">13.278</td>
<td valign="top" align="center">0.076718503</td>
<td valign="top" align="center">76.40710428</td>
<td valign="top" align="center">-</td>
<td valign="top" align="center"><bold>5.44</bold> <bold>&#x000B1;0.02</bold></td>
<td valign="top" align="center">5.13 &#x000B1; 0.1</td>
<td valign="top" align="center">4.85 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">2,6,6-trimethylcyclohexa-1,3-diene-1-carbaldehyde</td>
<td valign="top" align="center">107.1</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>14</sub>O</td>
<td valign="top" align="center">16.439</td>
<td valign="top" align="center">0.071249392</td>
<td valign="top" align="center">92.88423312</td>
<td valign="top" align="center">116-26-7</td>
<td valign="top" align="center">4.92 &#x000B1; 0.03</td>
<td valign="top" align="center">5.12 &#x000B1; 0.07</td>
<td valign="top" align="center"><bold>5.12</bold> <bold>&#x000B1;0.04</bold></td>
</tr> <tr>
<td valign="top" align="left">3-methylbutanoic acid</td>
<td valign="top" align="center">60</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>10</sub>O<sub>2</sub></td>
<td valign="top" align="center">17.024</td>
<td valign="top" align="center">0.062274418</td>
<td valign="top" align="center">85.17913453</td>
<td valign="top" align="center">503-74-2</td>
<td valign="top" align="center">6.02 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>6.09</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.88 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">2-methylbutanoic acid</td>
<td valign="top" align="center">74</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>10</sub>O<sub>2</sub></td>
<td valign="top" align="center">17.028</td>
<td valign="top" align="center">0.069051142</td>
<td valign="top" align="center">81.26700239</td>
<td valign="top" align="center">116-53-0</td>
<td valign="top" align="center">5.42 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>5.61</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.43 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">2,6,6-trimethylcyclohex-2-ene-1,4-dione</td>
<td valign="top" align="center">96.1</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>12</sub>O<sub>2</sub></td>
<td valign="top" align="center">17.081</td>
<td valign="top" align="center">0.059543144</td>
<td valign="top" align="center">75.47973568</td>
<td valign="top" align="center">1125-21-9</td>
<td valign="top" align="center">4.22 &#x000B1; 0.04</td>
<td valign="top" align="center"><bold>4.47</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">4.46 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">Pyrazine-2-carboxamide</td>
<td valign="top" align="center">80</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>5</sub>N<sub>3</sub>O</td>
<td valign="top" align="center">17.461</td>
<td valign="top" align="center">0.052748754</td>
<td valign="top" align="center">59.91665839</td>
<td valign="top" align="center">98-96-4</td>
<td valign="top" align="center">4.58 &#x000B1; 0.03</td>
<td valign="top" align="center">4.5 &#x000B1; 0.03</td>
<td valign="top" align="center"><bold>4.64</bold> <bold>&#x000B1;0.05</bold></td>
</tr> <tr>
<td valign="top" align="left">Valeric acid (<xref ref-type="bibr" rid="B84">84</xref>)</td>
<td valign="top" align="center">60.1</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>10</sub>O<sub>2</sub></td>
<td valign="top" align="center">18.642</td>
<td valign="top" align="center">0.058225562</td>
<td valign="top" align="center">91.46195141</td>
<td valign="top" align="center">109-52-4</td>
<td valign="top" align="center">5.18 &#x000B1; 0.05</td>
<td valign="top" align="center"><bold>5.42</bold> <bold>&#x000B1;0.04</bold></td>
<td valign="top" align="center">5.31 &#x000B1; 0.05</td>
</tr> <tr>
<td valign="top" align="left">2-phenylethanol (<xref ref-type="bibr" rid="B85">85</xref>)</td>
<td valign="top" align="center">91</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>10</sub>O</td>
<td valign="top" align="center">19.141</td>
<td valign="top" align="center">0.055682023</td>
<td valign="top" align="center">93.71279349</td>
<td valign="top" align="center">1960/12/8</td>
<td valign="top" align="center"><bold>5.27</bold> <bold>&#x000B1;0.03</bold></td>
<td valign="top" align="center">5.2 &#x000B1; 0.04</td>
<td valign="top" align="center">5.09 &#x000B1; 0.06</td>
</tr> <tr>
<td valign="top" align="left">2-butyloctan-1-ol</td>
<td valign="top" align="center">57</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>26</sub>O</td>
<td valign="top" align="center">19.318</td>
<td valign="top" align="center">0.059641269</td>
<td valign="top" align="center">72.8249512</td>
<td valign="top" align="center">3913/2/8</td>
<td valign="top" align="center">3.51 &#x000B1; 0.08</td>
<td valign="top" align="center"><bold>4.13</bold> <bold>&#x000B1;0.16</bold></td>
<td valign="top" align="center">4.07 &#x000B1; 0.06</td>
</tr> <tr>
<td valign="top" align="left">Hexadecanoic acid</td>
<td valign="top" align="center">74</td>
<td valign="top" align="left">C<sub>16</sub>H<sub>32</sub>O<sub>2</sub></td>
<td valign="top" align="center">21.219</td>
<td valign="top" align="center">0.058917775</td>
<td valign="top" align="center">82.23031131</td>
<td valign="top" align="center">1957/10/3</td>
<td valign="top" align="center">4.39 &#x000B1; 0.04</td>
<td valign="top" align="center">4.33 &#x000B1; 0.05</td>
<td valign="top" align="center"><bold>4.76</bold> <bold>&#x000B1;0.06</bold></td>
</tr> <tr>
<td valign="top" align="left">Diisobutyl phthalate</td>
<td valign="top" align="center">148.9</td>
<td valign="top" align="left">C<sub>16</sub>H<sub>22</sub>O<sub>4</sub></td>
<td valign="top" align="center">23.142</td>
<td valign="top" align="center">0.063856537</td>
<td valign="top" align="center">89.91536639</td>
<td valign="top" align="center">84-69-5</td>
<td valign="top" align="center"><bold>4.61</bold> <bold>&#x000B1;0.1</bold></td>
<td valign="top" align="center">4.13 &#x000B1; 0.06</td>
<td valign="top" align="center">4.26 &#x000B1; 0.04</td>
</tr> <tr>
<td valign="top" align="left">Palmitic acid (<xref ref-type="bibr" rid="B86">86</xref>)</td>
<td valign="top" align="center">73.1</td>
<td valign="top" align="left">C<sub>16</sub>H<sub>32</sub>O<sub>2</sub></td>
<td valign="top" align="center">26.354</td>
<td valign="top" align="center">0.098671895</td>
<td valign="top" align="center">87.30590317</td>
<td valign="top" align="center">1957/10/3</td>
<td valign="top" align="center">5.28 &#x000B1; 0.05</td>
<td valign="top" align="center">5.05 &#x000B1; 0.08</td>
<td valign="top" align="center"><bold>5.71</bold> <bold>&#x000B1;0.04</bold></td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>The bold values indicated the highest abundance.</p>
</table-wrap-foot>
</table-wrap>
</sec></sec>
<sec id="s4">
<title>4. Discussion</title>
<p><italic>P. palustre</italic> mainly contains polysaccharides, flavonoids, triterpenoids, phenolic acid, etc. (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B87">87</xref>). For evaluating the impact of different processing methods on the quality of <italic>P. palustre</italic>, we determined the contents of total sugar, soluble sugar, total pectin, and total flavonoids. In this study, we adopted three processing methods including sweating (M), tedding (S), and drying (H) to study the influences of different processing methods on the quality of <italic>P. palustre</italic>. The results indicated that the M treatment promoted the accumulation of the contents of total sugar, soluble sugar, and total pectin when compared with the H and S treatments (<xref ref-type="fig" rid="F2">Figure 2</xref>). It was inferred that the M treatment could promote the quality of <italic>P. palustre</italic>. It was also similar to the conclusion of Zhang et al. (<xref ref-type="bibr" rid="B16">16</xref>). During the sweating process, the external nutrient supply of <italic>P. palustre</italic> was cut off, and the tissue cells used nutrients such as polysaccharides stored internally for life activities. The polysaccharides might undergo hydrolysis reactions under the catalysis of hydrolytic enzymes, resulting in reduced molecular weight and improved water solubility of polysaccharides, which were manifested by an increase in the water-soluble polysaccharides. However, the total flavonoid content in the M treatment significantly decreased in comparison with the H and S treatments. It was inferred that the M treatment was not favorable to the improvement of total flavonoids. It was consistent with the results of Lu (<xref ref-type="bibr" rid="B18">18</xref>). Overall, the M treatment favored the improvement of the polysaccharide quality of <italic>P. palustre</italic>.</p>
<p>The metabolites of each treatment were also analyzed based on LC-MS. The results revealed that a total of 174 metabolites included phospholipids, monosaccharides, fatty acids, carboxylic acids, eicosanoids, amino acids, and vitamins were presented (<xref ref-type="supplementary-material" rid="SM2">Supplementary Table 1</xref>). Tang et al. (<xref ref-type="bibr" rid="B2">2</xref>) identified 184 metabolites in <italic>M. chinensis</italic> Benth by using LC-MS detection, which contained carbohydrates and carbohydrate conjugates, fatty acids and conjugates, eicosanoids, and so on. It was inferred that the number and type of metabolites identified in the present study were similar to the study by Tang et al. (<xref ref-type="bibr" rid="B2">2</xref>). This indicated that LC-MS technology was stable and suitable for the identification of <italic>P. palustre</italic> metabolites. Furthermore, we identified 98 differential metabolites among the three treatments. Notably, a total of 28, 51, and 19 metabolites presented the highest abundance in the H, M, and S treatments, respectively (<xref ref-type="table" rid="T1">Table 1</xref>). We could observe that the M treatment could promote the abundance of more than half of the differential metabolites (51 out of 98) in comparison with the H and S treatments. It was indicated that the M treatment could significantly change the type and abundance of metabolites of <italic>P. palustre</italic>. These changes might have significant impacts on the quality and flavor of this herbal medicine.</p>
<p>The content of polysaccharides is an important index for evaluating the quality of <italic>P. palustre</italic> (<xref ref-type="bibr" rid="B11">11</xref>). Zhang et al. (<xref ref-type="bibr" rid="B88">88</xref>) found that <italic>P. palustre</italic> polysaccharides consisted of eight monosaccharides, including galacturonic acid, glucose, galactose, xylose, mannose, rhamnose, ribose, and glucuronic acid. In this study, the relative abundances of sucrose, gluconic acid, D-(&#x0002B;)-trehalose, trehalose, and N-acetylmannosamine among the H, M, and S treatments were identified and analyzed. The abundances of gluconic acid and N-acetylmannosamine under three treatments were ranked as S&#x0003E;M&#x0003E;H, and the abundances of D-(&#x0002B;)-trehalose, sucrose, and trehalose were ranked as H&#x0003E;M&#x0003E;S (<xref ref-type="fig" rid="F4">Figure 4</xref>). This suggested that the M treatment was beneficial to the stability of the polysaccharide quality of <italic>P. palustre</italic>. Combined with the results in <xref ref-type="fig" rid="F2">Figures 2</xref>, <xref ref-type="fig" rid="F4">4</xref>, the M treatment seemed to be more favorable for the stability and improvement of the quality of <italic>P. palustre</italic> polysaccharides, although it decreased the content of total flavonoids.</p>
<p><italic>P. palustre</italic> is also rich in amino acids, and at least 18 types of amino acids including aspartic acid (Asp), threonine (Thr), serine (Ser), glutamic acid (Glu), glycine (Gly), cysteine (Cys), methionine (Met), valine (Val), isoleucine (Ile), tyrosine (Tyr), phenylalanine (Phe), lysine (Lys), histidine (His), arginine (Arg), proline (Pro), alanine (Ala), leucine (Leu), and tryptophan (Trp) were determined by Liu and Chen (<xref ref-type="bibr" rid="B89">89</xref>). Similarly, Su et al. (<xref ref-type="bibr" rid="B78">78</xref>) reported 17 types of amino acids in <italic>P. palustre</italic> from different production areas, which were almost the same with the results of Liu and Chen (<xref ref-type="bibr" rid="B89">89</xref>). In this study, we identified 11 differential amino acids, such as L-dopa, L-proline, L-alanine, L-glutamine, L-phenylalanine, L-threonine, L-(&#x0002B;)-arginine, beta-alanine, L-tryptophan, L-tyrosine, and aspartic Acid, and the abundances of nine amino acids significantly increased in the H treatment (<xref ref-type="fig" rid="F5">Figure 5</xref>). It was indicated that the H treatments could significantly change the abundances of the most differential amino acids in <italic>P. palustre</italic>. This might be because that the relatively high-temperature condition (50&#x000B0;C) in the H treatment promoted the degradation of protein into amino acids, thereby increasing the expression abundance of amino acids, thus improving their nutritional levels. In addition, since Asp and Glu are delicious amino acids, and Ala, Ser, and Gly are sweet amino acids in <italic>P. palustre</italic> (<xref ref-type="bibr" rid="B78">78</xref>). The abundances of aspartic acid and L-alanine in the H treatment were significantly increased compared with the M and S treatments, indicating that the H treatment could promote the flavor level of <italic>P. palustre</italic>. Therefore, in general, the H treatment could improve the nutrition and flavor level of <italic>P. palustre</italic>.</p>
<p>Volatile oil, or essential oil, is a general term used for oily liquids that are volatile and can be distilled with steam (<xref ref-type="bibr" rid="B90">90</xref>), and has various effects such as antibacterial (<xref ref-type="bibr" rid="B91">91</xref>), anti-inflammatory (<xref ref-type="bibr" rid="B92">92</xref>), and antitumor (<xref ref-type="bibr" rid="B93">93</xref>). Volatile oil is widely found in herbal medicines such as <italic>P. palustre</italic> (<xref ref-type="bibr" rid="B17">17</xref>). Lu et al. (<xref ref-type="bibr" rid="B12">12</xref>) identified 24 types of volatile constituents from Taiwan <italic>Mesona chinensis</italic> Benth, while Xu and Wei (<xref ref-type="bibr" rid="B94">94</xref>) found 56, 54, and 58 types of volatile flavor compounds in Vietnam, Thailand, and Indonesia, respectively. Wei et al. (<xref ref-type="bibr" rid="B95">95</xref>) extracted and detected 59 volatile components from the water-soluble extract of <italic>Mesona Benth</italic> prepared by the solvent extraction method, while Chen et al. (<xref ref-type="bibr" rid="B96">96</xref>) identified 40 and 34 volatile components using supercritical CO<sub>2</sub> extraction and hydrodistillation methods, respectively. Kung et al. (<xref ref-type="bibr" rid="B97">97</xref>) determined 56 and 108 volatile components using headspace solid-phase microextraction (HS-SPME) and simultaneous distillation&#x02013;extraction (SDE), respectively. In this study, a total of 55 volatile substances were identified in HMDB by HS-GC-MS (<xref ref-type="supplementary-material" rid="SM2">Supplementary Table 4</xref>). It was inferred that different volatile components of <italic>P. palustre</italic> could be obtained from different varieties (or regional sources) and different extraction methods and technologies. Furthermore, the main volatile compounds identified in <italic>P. palustre</italic> were alkenes, alcohols, ketones, aldehydes, and phenols (<xref ref-type="bibr" rid="B95">95</xref>) or alkenes, ketones, alkanes, and fatty acids (<xref ref-type="bibr" rid="B98">98</xref>), or terpenoids and carbonyl compounds (<xref ref-type="bibr" rid="B94">94</xref>). In the present study, the volatile substances identified mainly included organic oxygen compounds (17, 30.91%), lipids and lipid-like molecules (15, 27.27%), organic acids and derivatives (8, 14.55%), organoheterocyclic compounds (8, 14.55%), benzenoids (6, 10.91%), and hydrocarbons (1, 1.82%; <xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 8</xref>; <xref ref-type="supplementary-material" rid="SM2">Supplementary Table 4</xref>). In general, the volatile components identified in this study were similar to those previously reported, although there were some differences. This might be caused by the different experimental materials, different experimental treatments, and different sample pretreatments. In particular, we identified 27 differential volatile substances among the H, M, and S treatments, and there were 11, 9, and 7 differential volatile substances showing the highest abundance in the H, M, and S treatments, respectively (<xref ref-type="table" rid="T2">Table 2</xref>). It was inferred that different processing methods had a great impact on the volatile substances in <italic>P. palustre</italic>, especially the M treatment. The fermentation in the H treatment, the constant temperature (50&#x000B0;C) in the H treatment, and the variable temperature in the S treatment might account for the differences in volatile substances in <italic>P. palustre</italic>.</p></sec>
<sec id="s5">
<title>5. Conclusion</title>
<p>To study the effects of different processing methods on the quality, nutrition, and flavor of <italic>Platostoma palustre</italic>, we adopted the LC-MS and HS-GC-MS methods to compare the effects of tedding (S), sweating (M), and drying (H) on the metabolites and volatile substances of <italic>P. palustre</italic>. The results showed that the M treatment facilitated the stabilization and improvement of the polysaccharide and volatile substances quality of <italic>P. palustre</italic>, while the H treatment could promote the nutrition level of <italic>P. palustre</italic>. Considering the quality of polysaccharides and volatile substances, the M treatment was the optimal processing method for <italic>P. palustre</italic>. This study provides a theoretical reference for establishing standardized processing methods and maintaining the quality stability of <italic>P. palustre</italic> in future.</p></sec>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref>, further inquiries can be directed to the corresponding author.</p></sec>
<sec sec-type="author-contributions" id="s7">
<title>Author contributions</title>
<p>DT: conceptualization, methodology, data curation, formal analysis, writing&#x02014;original draft, writing&#x02014;reviewing and editing, and funding acquisition. FW: supervision, methodology, writing&#x02014;reviewing and editing, and funding acquisition. CQ and SH: software, data curation, and formal analysis. All authors contributed to the article and approved the submitted version.</p></sec>
</body>
<back>
<sec sec-type="funding-information" id="s8">
<title>Funding</title>
<p>This study was supported by the Fund Projects of the Central Government in Guidance of Local Science and Technology Development (GuiKeZY22096020), the National Natural Science Foundation of China (82260750 and 82260749), the Appropriate Technology Development and Promotion Project of Guangxi Traditional Chinese Medicine Administration (GZSY23-07), Guangxi Elite Team of Medicinal Mlant Conservation (2023), and the Scientific Research Funding Project of Guangxi Botanical Garden of Medicinal Plants (GuiYaoJi202011).</p>
</sec>
<ack><p>The authors thank Guangxi Elite Team of Medicinal Plant Conservation (2023).</p>
</ack>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="s9">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="s10">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1181942/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fnut.2023.1181942/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.xlsx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.spreadsheetml.sheet" xmlns:xlink="http://www.w3.org/1999/xlink"/>
<supplementary-material xlink:href="Data_Sheet_1.docx" id="SM2" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
<ref-list>
<title>References</title>
<ref id="B1">
<label>1.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname> <given-names>DF</given-names></name> <name><surname>Lin</surname> <given-names>Y</given-names></name> <name><surname>Wei</surname> <given-names>F</given-names></name> <name><surname>Quan</surname> <given-names>CQ</given-names></name> <name><surname>Wei</surname> <given-names>KH</given-names></name> <name><surname>Wei</surname> <given-names>YY</given-names></name> <etal/></person-group>. <article-title>Characteristics and comparative analysis of <italic>Mesona chinensis</italic> Benth chloroplast genome reveal DNA barcode regions for species identification</article-title>. <source>Funct Integr Genomics.</source> (<year>2022</year>) <volume>22</volume>:<fpage>467</fpage>&#x02013;<lpage>79</lpage>. <pub-id pub-id-type="doi">10.1007/s10142-022-00846-8</pub-id><pub-id pub-id-type="pmid">35318559</pub-id></citation></ref>
<ref id="B2">
<label>2.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname> <given-names>DF</given-names></name> <name><surname>Huang</surname> <given-names>QF</given-names></name> <name><surname>Wei</surname> <given-names>KH</given-names></name> <name><surname>Yang</surname> <given-names>XN</given-names></name> <name><surname>Wei</surname> <given-names>F</given-names></name> <name><surname>Miao</surname> <given-names>JH</given-names></name></person-group>. <article-title>Identification of differentially expressed genes and pathways involved in growth and development of <italic>Mesona chinensis</italic> Benth under red and blue light conditions</article-title>. <source>Front Plant Sci.</source> (<year>2021</year>) <volume>12</volume>:<fpage>761068</fpage>. <pub-id pub-id-type="doi">10.3389/fpls.2021.761068</pub-id><pub-id pub-id-type="pmid">34899784</pub-id></citation></ref>
<ref id="B3">
<label>3.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname> <given-names>DF</given-names></name> <name><surname>Quan</surname> <given-names>CQ</given-names></name> <name><surname>Wei</surname> <given-names>KH</given-names></name> <name><surname>Lin</surname> <given-names>Y</given-names></name> <name><surname>Huang</surname> <given-names>QF</given-names></name> <name><surname>Wei</surname> <given-names>F</given-names></name> <etal/></person-group>. <article-title>Physio-morphological, biochemical and transcriptomic analyses provide insights into drought stress responses in <italic>Mesona chinensis</italic> Benth</article-title>. <source>Front Plant Sci.</source> (<year>2022</year>) <volume>13</volume>:<fpage>809723</fpage>. <pub-id pub-id-type="doi">10.3389/fpls.2022.809723</pub-id><pub-id pub-id-type="pmid">35222473</pub-id></citation></ref>
<ref id="B4">
<label>4.</label>
<citation citation-type="book"><person-group person-group-type="author"><collab>Chinese Materia Medica</collab></person-group>. <source>Editorial Board of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine. Volume 19</source>. <publisher-loc>Shanghai</publisher-loc>: <publisher-name>Shanghai Science and Technology Press.</publisher-name> (<year>1999</year>). <fpage>p. 421</fpage>.</citation>
</ref>
<ref id="B5">
<label>5.</label>
<citation citation-type="book"><person-group person-group-type="author"><collab>Dictionary of Traditional Chinese Medicine</collab></person-group>. <source>Nanjing University of Traditional Chinese Medicine</source>. <publisher-loc>Shanghai</publisher-loc>: <publisher-name>Shanghai Science and Technology Press.</publisher-name> (<year>2006</year>).</citation>
</ref>
<ref id="B6">
<label>6.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yen</surname> <given-names>GC</given-names></name> <name><surname>Hung</surname> <given-names>CY</given-names></name></person-group>. <article-title>Effects of alkaline and heat treatment on antioxidative activity and total henolics of extract from Hsian-tsao (<italic>Mesona procumbens</italic> Hemsl)</article-title>. <source>Food ResInt.</source> (<year>2000</year>) <volume>33</volume>:<fpage>487</fpage>&#x02013;<lpage>92</lpage>. <pub-id pub-id-type="doi">10.1016/S0963-9969(00)00073-9</pub-id></citation>
</ref>
<ref id="B7">
<label>7.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yeha</surname> <given-names>CT</given-names></name> <name><surname>Huang</surname> <given-names>WH</given-names></name> <name><surname>Yen</surname> <given-names>GC</given-names></name></person-group>. <article-title>Antihypertensive effects of Hsian-tsao and its active compound in spontaneously hypertensive rats</article-title>. <source>J Nutrit Biochem.</source> (<year>2009</year>) <volume>20</volume>:<fpage>866</fpage>&#x02013;<lpage>75</lpage>. <pub-id pub-id-type="doi">10.1016/j.jnutbio.2008.07.015</pub-id><pub-id pub-id-type="pmid">18993049</pub-id></citation></ref>
<ref id="B8">
<label>8.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname> <given-names>FL</given-names></name> <name><surname>Feng</surname> <given-names>CL</given-names></name></person-group>. <article-title><italic>In vitro</italic> antibacterial test of Hsian-tsao (<italic>Mesona chinensis</italic> Benth) against avian <italic>Escherichia coli</italic></article-title>. <source>Guangdong J Anim Vet Sci</source>. (<year>2008</year>) <volume>33</volume>:<fpage>17</fpage>&#x02013;<lpage>43</lpage>.</citation>
</ref>
<ref id="B9">
<label>9.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Li</surname> <given-names>DY</given-names></name> <name><surname>Lu</surname> <given-names>G</given-names></name> <name><surname>Wang</surname> <given-names>DD</given-names></name> <name><surname>Wang</surname> <given-names>M</given-names></name></person-group>. <article-title>The influence of Xiancao hypolipidemic tea on the TC and TG metabolism of the experimental rabbits</article-title>. <source>Chin General Practice.</source> (<year>2010</year>) <volume>13</volume>:<fpage>9</fpage>&#x02013;<lpage>10</lpage>.</citation>
</ref>
<ref id="B10">
<label>10.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname> <given-names>LH</given-names></name> <name><surname>Huang</surname> <given-names>LC</given-names></name> <name><surname>Xie</surname> <given-names>JH</given-names></name></person-group>. <article-title>Review on main chemical constituents and biological activities of <italic>Mesona chinensis</italic></article-title>. <source>Sci Technol Food Industry</source>. (<year>2016</year>) <volume>37</volume>:<fpage>356</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.13386/j.issn1002-0306.2016.20.063</pub-id></citation>
</ref>
<ref id="B11">
<label>11.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname> <given-names>LS</given-names></name> <name><surname>Zhang</surname> <given-names>S</given-names></name> <name><surname>Chan</surname> <given-names>YL</given-names></name> <name><surname>Wang</surname> <given-names>ZK</given-names></name> <name><surname>Lin</surname> <given-names>HT</given-names></name></person-group>. <article-title>A review of chemical constituents and medicinal function of <italic>Mesona chinensis</italic> Benth</article-title>. <source>Current Biotechnology.</source> (<year>2013</year>) <volume>3</volume>:<fpage>448</fpage>&#x02013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.3969/j.issn.20952341.2013.06.14</pub-id></citation>
</ref>
<ref id="B12">
<label>12.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lu</surname> <given-names>XY</given-names></name> <name><surname>Lin</surname> <given-names>CQ</given-names></name> <name><surname>Lai</surname> <given-names>ZM</given-names></name> <name><surname>Jiang</surname> <given-names>XX</given-names></name> <name><surname>Yan</surname> <given-names>P</given-names></name> <name><surname>Zhan</surname> <given-names>RT</given-names></name></person-group>. <article-title>Analysis of volatile constituents from <italic>Mesona chinensis</italic> Benth. by HS- GC-MS</article-title>. <source>J Guangzhou Univ Trad Chin Med.</source> (<year>2021</year>) <volume>38</volume>:<fpage>1025</fpage>&#x02013;<lpage>31</lpage>. <pub-id pub-id-type="doi">10.13359/j.cnki.gzxbtcm.2021.05.029</pub-id></citation>
</ref>
<ref id="B13">
<label>13.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname> <given-names>DF</given-names></name> <name><surname>Wei</surname> <given-names>F</given-names></name> <name><surname>Quan</surname> <given-names>CQ</given-names></name> <name><surname>Huang</surname> <given-names>SH</given-names></name> <name><surname>Huang</surname> <given-names>Y</given-names></name> <name><surname>Wei</surname> <given-names>KH</given-names></name> <etal/></person-group>. <article-title>Codon usage bias and evolution analysis in the mitochondrial genome of <italic>Mesona chinensis</italic> Benth</article-title>. <source>Acta Physiologiae Plantarum.</source> (<year>2022</year>) <volume>44</volume>:<fpage>118</fpage>. <pub-id pub-id-type="doi">10.1007/s11738-022-03453-z</pub-id></citation>
</ref>
<ref id="B14">
<label>14.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname> <given-names>ML</given-names></name> <name><surname>Liu</surname> <given-names>A</given-names></name> <name><surname>Chen</surname> <given-names>YW</given-names></name></person-group>. <article-title>Study on the influence of Chinese medicinal materials and its processing on the efficacy of traditional Chinese drugs</article-title>. <source>Guid J Trad Chin Med Pharm.</source> (<year>2015</year>) <volume>21</volume>:<fpage>26</fpage>&#x02013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.13862/j.cnki.cn43-1446/r.2015.08.008</pub-id></citation>
</ref>
<ref id="B15">
<label>15.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname> <given-names>HL</given-names></name> <name><surname>Wei</surname> <given-names>YF</given-names></name> <name><surname>Ma</surname> <given-names>XW</given-names></name> <name><surname>Pan</surname> <given-names>L</given-names></name> <name><surname>Yan</surname> <given-names>J</given-names></name> <name><surname>Lu</surname> <given-names>JR</given-names></name></person-group>. <article-title>Effect of different processing methods on the contents of the main chemical constituents of <italic>Magnolia officinalis</italic> Cortex</article-title>. <source>Chin Trad Pat Med.</source> (<year>2011</year>) <volume>33</volume>:<fpage>834</fpage>&#x02013;<lpage>7</lpage>.</citation>
</ref>
<ref id="B16">
<label>16.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>P</given-names></name> <name><surname>Zheng</surname> <given-names>ZA</given-names></name> <name><surname>Jiang</surname> <given-names>QW</given-names></name></person-group>. <article-title>Effects of different pretreatment methods on quality and drying characteristics of <italic>Poria cocos</italic> after harvest</article-title>. <source>Trans Chin Soc Agri Eng.</source> (<year>2018</year>) <volume>34</volume>:<fpage>294</fpage>&#x02013;<lpage>304</lpage>.</citation>
</ref>
<ref id="B17">
<label>17.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname> <given-names>BC</given-names></name> <name><surname>Chen</surname> <given-names>JY</given-names></name> <name><surname>Huang</surname> <given-names>YZ</given-names></name> <name><surname>Zhao</surname> <given-names>YQ</given-names></name> <name><surname>Cai</surname> <given-names>SZ</given-names></name></person-group>. <article-title>Current status and future development of <italic>Mesona chinensis</italic> Benth agriculture</article-title>. <source>Fujian J Agri Sci.</source> (<year>2015</year>) <volume>30</volume>:<fpage>718</fpage>&#x02013;<lpage>25</lpage>. <pub-id pub-id-type="doi">10.13651/j.cnki.fjnykj.2015.05.019</pub-id><pub-id pub-id-type="pmid">6404524</pub-id></citation></ref>
<ref id="B18">
<label>18.</label>
<citation citation-type="book"><person-group person-group-type="author"><name><surname>Lu</surname> <given-names>XY</given-names></name></person-group>. <source>Study on Effects of Processing Methods on the Quality of Mesona chinensis Benth and Its Lipid-Lowering Activity in vitro</source>. <publisher-loc>Guangzhou</publisher-loc>: <publisher-name>Guangzhou University of Chinese Medicine</publisher-name> (<year>2020</year>).</citation>
</ref>
<ref id="B19">
<label>19.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xie</surname> <given-names>M</given-names></name> <name><surname>Chen</surname> <given-names>W</given-names></name> <name><surname>Lai</surname> <given-names>X</given-names></name> <name><surname>Dai</surname> <given-names>H</given-names></name> <name><surname>Sun</surname> <given-names>H</given-names></name> <name><surname>Zhou</surname> <given-names>X</given-names></name> <etal/></person-group>. <article-title>Metabolic responses and their correlations with phytochelatins in <italic>Amaranthus hypochondriacus</italic> under cadmium stress</article-title>. <source>Environ Pollut.</source> (<year>2019</year>) <volume>252</volume>:<fpage>1791</fpage>&#x02013;<lpage>800</lpage>. <pub-id pub-id-type="doi">10.1016/j.envpol.2019.06.103</pub-id><pub-id pub-id-type="pmid">31299508</pub-id></citation></ref>
<ref id="B20">
<label>20.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kong</surname> <given-names>XG</given-names></name> <name><surname>Guo</surname> <given-names>ZA</given-names></name> <name><surname>Yao</surname> <given-names>Y</given-names></name> <name><surname>Xia</surname> <given-names>LC</given-names></name> <name><surname>Liu</surname> <given-names>RX</given-names></name> <name><surname>Song</surname> <given-names>HF</given-names></name> <etal/></person-group>. <article-title>Acetic acid alters rhizosphere microbes and metabolic composition to improve willows drought resistance</article-title>. <source>Sci Tot Environ.</source> (<year>2022</year>) <volume>844</volume>:<fpage>157132</fpage>. <pub-id pub-id-type="doi">10.1016/j.scitotenv.2022.157132</pub-id><pub-id pub-id-type="pmid">35798115</pub-id></citation></ref>
<ref id="B21">
<label>21.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Dong</surname> <given-names>XY</given-names></name> <name><surname>Mu</surname> <given-names>QX</given-names></name> <name><surname>Song</surname> <given-names>LL</given-names></name> <name><surname>Liu</surname> <given-names>BY</given-names></name> <name><surname>Zhang</surname> <given-names>LH</given-names></name> <name><surname>Wang</surname> <given-names>YF</given-names></name></person-group>. <article-title>Study on discrimination of <italic>Decoction pieces</italic> from Rutaceae by HS-GC-MS</article-title>. <source>J Chin Med Mater.</source> (<year>2022</year>) <volume>45</volume>:<fpage>2920</fpage>&#x02013;<lpage>5</lpage>.</citation>
</ref>
<ref id="B22">
<label>22.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Andreesen</surname> <given-names>R</given-names></name> <name><surname>Osterholz</surname> <given-names>J</given-names></name> <name><surname>Luckenbach</surname> <given-names>GA</given-names></name> <name><surname>Costabel</surname> <given-names>U</given-names></name> <name><surname>Schulz</surname> <given-names>A</given-names></name> <name><surname>Speth</surname> <given-names>V</given-names></name> <etal/></person-group>. <article-title>Tumor cytotoxicity of human macrophages after incubation with synthetic analogues of 2-lysophosphatidylcholine</article-title>. <source>J Natl Cancer I.</source> (<year>1984</year>) <volume>72</volume>:<fpage>53</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1093/jnci/72.1.53</pub-id><pub-id pub-id-type="pmid">6582303</pub-id></citation></ref>
<ref id="B23">
<label>23.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gorska-Ponikowska</surname> <given-names>M</given-names></name> <name><surname>Kuban-Jankowska</surname> <given-names>A</given-names></name> <name><surname>Daca</surname> <given-names>A</given-names></name> <name><surname>Nussberger</surname> <given-names>S</given-names></name></person-group>. <article-title>2-Methoxyestradiol reverses the pro-carcinogenic effect of L-Lactate in Osteosarcoma 143B cells</article-title>. <source>Cancer Genom Proteom.</source> (<year>2017</year>) <volume>14</volume>:<fpage>483</fpage>&#x02013;<lpage>93</lpage>. <pub-id pub-id-type="doi">10.21873/cgp.20058</pub-id><pub-id pub-id-type="pmid">29109098</pub-id></citation></ref>
<ref id="B24">
<label>24.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Whitehead</surname> <given-names>A</given-names></name> <name><surname>Krause</surname> <given-names>FN</given-names></name> <name><surname>Moran</surname> <given-names>A</given-names></name> <name><surname>Maccannell</surname> <given-names>A</given-names></name> <name><surname>Roberts</surname> <given-names>LD</given-names></name></person-group>. <article-title>Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis</article-title>. <source>Nat Commun.</source> (<year>2021</year>) <volume>12</volume>:<fpage>1905</fpage>. <pub-id pub-id-type="doi">10.1038/s41467-021-22272-3</pub-id><pub-id pub-id-type="pmid">33772024</pub-id></citation></ref>
<ref id="B25">
<label>25.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname> <given-names>J</given-names></name> <name><surname>Zheng</surname> <given-names>X</given-names></name> <name><surname>Haugen</surname> <given-names>F</given-names></name> <name><surname>Dar&#x000E8;</surname> <given-names>E</given-names></name> <name><surname>Lvdahl</surname> <given-names>C</given-names></name> <name><surname>Schulte</surname> <given-names>G</given-names></name> <etal/></person-group>. <article-title>Adenosine increases LPS-induced nuclear factor kappa B activation in smooth muscle cells via an intracellular mechanism and modulates it via actions on adenosine receptors</article-title>. <source>Acta Physiol.</source> (<year>2013</year>) <volume>210</volume>:<fpage>590</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1111/apha.12176</pub-id><pub-id pub-id-type="pmid">24119187</pub-id></citation></ref>
<ref id="B26">
<label>26.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yamaguchi</surname> <given-names>Y</given-names></name> <name><surname>Yamamoto</surname> <given-names>K</given-names></name> <name><surname>Sato</surname> <given-names>Y</given-names></name> <name><surname>Inoue</surname> <given-names>S</given-names></name> <name><surname>Morinaga</surname> <given-names>T</given-names></name> <name><surname>Hirano</surname> <given-names>E</given-names></name></person-group>. <article-title>Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation</article-title>. <source>Biomed Res-Tokyo.</source> (<year>2016</year>) <volume>37</volume>:<fpage>153</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.2220/biomedres.37.153</pub-id><pub-id pub-id-type="pmid">27108884</pub-id></citation></ref>
<ref id="B27">
<label>27.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname> <given-names>SY</given-names></name> <name><surname>Kim</surname> <given-names>YC</given-names></name></person-group>. <article-title>Effect of beta-alanine administration on carbon tetrachloride-induced acute hepatotoxicity</article-title>. <source>Amino Acids.</source> (<year>2006</year>) <volume>33</volume>:<fpage>543</fpage>&#x02013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1007/s00726-006-0450-7</pub-id><pub-id pub-id-type="pmid">17086479</pub-id></citation></ref>
<ref id="B28">
<label>28.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Nakagawa</surname> <given-names>Y</given-names></name> <name><surname>Nishikawa</surname> <given-names>B</given-names></name> <name><surname>Miyagawa</surname> <given-names>H</given-names></name></person-group>. <article-title>Effects of brassinolide on the growing of rice plants</article-title>. <source>J Pestic Sci.</source> (<year>2021</year>) <volume>46</volume>:<fpage>274</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1584/jpestics.D21-024</pub-id><pub-id pub-id-type="pmid">34566461</pub-id></citation></ref>
<ref id="B29">
<label>29.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fang</surname> <given-names>K</given-names></name> <name><surname>Zhan</surname> <given-names>Y</given-names></name> <name><surname>Zhu</surname> <given-names>R</given-names></name> <name><surname>Wang</surname> <given-names>YQ</given-names></name> <name><surname>Wu</surname> <given-names>CQ</given-names></name> <name><surname>Sun</surname> <given-names>M</given-names></name> <etal/></person-group>. <article-title>Bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway</article-title>. <source>J Transl Med.</source> (<year>2021</year>) <volume>19</volume>:<fpage>383</fpage>. <pub-id pub-id-type="doi">10.1186/s12967-021-03058-z</pub-id><pub-id pub-id-type="pmid">34496870</pub-id></citation></ref>
<ref id="B30">
<label>30.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Manrique-Vergara</surname> <given-names>D</given-names></name> <name><surname>Gonz&#x000E1;lez-S&#x000E1;nchez</surname> <given-names>ME</given-names></name></person-group>. <article-title>Short chain fatty acids (butyric acid) and intestinal diseases</article-title>. <source>Nutr Hosp.</source> (<year>2017</year>) <volume>34</volume>:<fpage>58</fpage>&#x02013;<lpage>61</lpage>. <pub-id pub-id-type="doi">10.20960/nh.1573</pub-id><pub-id pub-id-type="pmid">29156934</pub-id></citation></ref>
<ref id="B31">
<label>31.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Newman</surname> <given-names>WH</given-names></name> <name><surname>Castresana</surname> <given-names>MR</given-names></name> <name><surname>Webb</surname> <given-names>JG</given-names></name> <name><surname>Wang</surname> <given-names>Z</given-names></name></person-group>. <article-title>Cyclic AMP inhibits production of interleukin-6 and migration in human vascular smooth muscle cells</article-title>. <source>J Surg Res.</source> (<year>2003</year>) <volume>109</volume>:<fpage>57</fpage>&#x02013;<lpage>61</lpage>. <pub-id pub-id-type="doi">10.1016/S0022-4804(02)00038-0</pub-id><pub-id pub-id-type="pmid">12591236</pub-id></citation></ref>
<ref id="B32">
<label>32.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Baswan</surname> <given-names>SM</given-names></name> <name><surname>Leverett</surname> <given-names>J</given-names></name> <name><surname>Pawelek</surname> <given-names>J</given-names></name></person-group>. <article-title>Clinical evaluation of the lightening effect of cytidine on hyperpigmented skin</article-title>. <source>J Cosmet Dermatol-US.</source> (<year>2018</year>) <volume>18</volume>:<fpage>278</fpage>&#x02013;<lpage>85</lpage>. <pub-id pub-id-type="doi">10.1111/jocd.12784</pub-id><pub-id pub-id-type="pmid">30291682</pub-id></citation></ref>
<ref id="B33">
<label>33.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Nazari-Robati</surname> <given-names>M</given-names></name> <name><surname>Akbari</surname> <given-names>M</given-names></name> <name><surname>Khaksari</surname> <given-names>M</given-names></name> <name><surname>Mirzaee</surname> <given-names>M</given-names></name></person-group>. <article-title>Trehalose attenuates spinal cord injury through the regulation of oxidative stress, inflammation and GFAP expression in rats</article-title>. <source>J Spinal Cord Med.</source> (<year>2018</year>) <volume>42</volume>:<fpage>387</fpage>&#x02013;<lpage>94</lpage>. <pub-id pub-id-type="doi">10.1080/10790268.2018.1527077</pub-id><pub-id pub-id-type="pmid">30513271</pub-id></citation></ref>
<ref id="B34">
<label>34.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Jim&#x000E9;nez</surname> <given-names>MC</given-names></name> <name><surname>Sun</surname> <given-names>Q</given-names></name> <name><surname>Sch&#x000FC;rks</surname> <given-names>M</given-names></name> <name><surname>Chiuve</surname> <given-names>S</given-names></name> <name><surname>Hu</surname> <given-names>FB</given-names></name> <name><surname>Manson</surname> <given-names>JE</given-names></name> <etal/></person-group>. <article-title>Low dehydroepiandrosterone sulfate is associated with increased risk of ischemic stroke among women</article-title>. <source>Stroke.</source> (<year>2013</year>) <volume>44</volume>:<fpage>1784</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1161/STROKEAHA.111.000485</pub-id><pub-id pub-id-type="pmid">23704104</pub-id></citation></ref>
<ref id="B35">
<label>35.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Martiniova</surname> <given-names>L</given-names></name> <name><surname>Field</surname> <given-names>MS</given-names></name> <name><surname>Finkelstein</surname> <given-names>JL</given-names></name> <name><surname>Perry</surname> <given-names>CA</given-names></name> <name><surname>Stover</surname> <given-names>PJ</given-names></name></person-group>. <article-title>Maternal dietary uridine causes, and deoxyuridine prevents, neural tube closure defects in a mouse model of folate-responsive neural tube defects</article-title>. <source>Am J Clin Nutr.</source> (<year>2015</year>) <volume>101</volume>:<fpage>860</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.3945/ajcn.114.097279</pub-id><pub-id pub-id-type="pmid">25833982</pub-id></citation></ref>
<ref id="B36">
<label>36.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname> <given-names>S</given-names></name> <name><surname>Fan</surname> <given-names>J</given-names></name> <name><surname>Wang</surname> <given-names>Q</given-names></name> <name><surname>Ju</surname> <given-names>DW</given-names></name> <name><surname>Feng</surname> <given-names>MQ</given-names></name> <name><surname>Li</surname> <given-names>JY</given-names></name> <etal/></person-group>. <article-title>Diosgenin induces ROS-dependent autophagy and cytotoxicity via mTOR signaling pathway in chronic myeloid leukemia cells</article-title>. <source>Phytomedicine</source>. (<year>2016</year>) <volume>23</volume>:<fpage>243</fpage>&#x02013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.1016/j.phymed.2016.01.010</pub-id><pub-id pub-id-type="pmid">26969378</pub-id></citation></ref>
<ref id="B37">
<label>37.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Dreyer</surname> <given-names>G</given-names></name> <name><surname>Kieswich</surname> <given-names>J</given-names></name> <name><surname>Harwood</surname> <given-names>S</given-names></name> <name><surname>Ahluwalia</surname> <given-names>A</given-names></name> <name><surname>Yaqoob</surname> <given-names>MM</given-names></name></person-group>. <article-title>Ergocalciferol improves endothelial vasodilatory and vasoconstrictor function in an <italic>in vivo</italic> model of mild uraemia</article-title>. <source>Bioscience Rep</source>. (<year>2019</year>) <volume>39</volume>:<fpage>BSR20190711</fpage>. <pub-id pub-id-type="doi">10.1042/BSR20190711</pub-id><pub-id pub-id-type="pmid">31789348</pub-id></citation></ref>
<ref id="B38">
<label>38.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Crescitelli</surname> <given-names>MC</given-names></name> <name><surname>Rauschemberger</surname> <given-names>MB</given-names></name> <name><surname>Cepeda</surname> <given-names>S</given-names></name> <name><surname>Sandoval</surname> <given-names>M</given-names></name> <name><surname>Massheimer</surname> <given-names>VL</given-names></name></person-group>. <article-title>Role of estrone on the regulation of osteoblastogenesis</article-title>. <source>Mol Cell Endocrinol.</source> (<year>2019</year>) <volume>498</volume>:<fpage>110582</fpage>. <pub-id pub-id-type="doi">10.1016/j.mce.2019.110582</pub-id><pub-id pub-id-type="pmid">31525430</pub-id></citation></ref>
<ref id="B39">
<label>39.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Manaenko</surname> <given-names>A</given-names></name> <name><surname>Fathali</surname> <given-names>N</given-names></name> <name><surname>Chen</surname> <given-names>H</given-names></name> <name><surname>Suzuki</surname> <given-names>H</given-names></name> <name><surname>Williams</surname> <given-names>S</given-names></name> <name><surname>Zhang</surname> <given-names>JH</given-names></name> <etal/></person-group>. <article-title>Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage</article-title>. <source>Neurochem Int.</source> (<year>2010</year>) <volume>57</volume>:<fpage>844</fpage>&#x02013;<lpage>50</lpage>. <pub-id pub-id-type="doi">10.1016/j.neuint.2010.09.001</pub-id><pub-id pub-id-type="pmid">20849898</pub-id></citation></ref>
<ref id="B40">
<label>40.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Michiels</surname> <given-names>J</given-names></name> <name><surname>Truffin</surname> <given-names>D</given-names></name> <name><surname>Majdeddin</surname> <given-names>M</given-names></name> <name><surname>Van Poucke</surname> <given-names>M</given-names></name> <name><surname>Van Liefferinge</surname> <given-names>E</given-names></name> <name><surname>Van Noten</surname> <given-names>N</given-names></name> <etal/></person-group>. <article-title>Gluconic acid improves performance of newly weaned piglets associated with alterations in gut microbiome and fermentation</article-title>. <source>Porcine Health Manag.</source> (<year>2023</year>) <volume>9</volume>:<fpage>10</fpage>. <pub-id pub-id-type="doi">10.1186/s40813-023-00305-1</pub-id><pub-id pub-id-type="pmid">37016456</pub-id></citation></ref>
<ref id="B41">
<label>41.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>de Oliveira</surname> <given-names>ED</given-names></name> <name><surname>Schallenberger</surname> <given-names>C</given-names></name> <name><surname>B&#x000F6;hmer</surname> <given-names>AE</given-names></name> <name><surname>Hansel</surname> <given-names>G</given-names></name> <name><surname>Schmidt</surname> <given-names>AP</given-names></name></person-group>. <article-title>Mechanisms involved in the antinociception induced by spinal administration of inosine or guanine in mice</article-title>. <source>Eur J Pharmacol.</source> (<year>2015</year>) <volume>772</volume>:<fpage>71</fpage>&#x02013;<lpage>82</lpage>. <pub-id pub-id-type="doi">10.1016/j.ejphar.2015.12.034</pub-id><pub-id pub-id-type="pmid">26712379</pub-id></citation></ref>
<ref id="B42">
<label>42.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Camargo</surname> <given-names>A</given-names></name> <name><surname>Dalmagro</surname> <given-names>AP</given-names></name> <name><surname>Fraga</surname> <given-names>DB</given-names></name> <name><surname>Rosa</surname> <given-names>JM</given-names></name> <name><surname>Zeni</surname> <given-names>ALB</given-names></name> <name><surname>Kaster</surname> <given-names>MP</given-names></name> <etal/></person-group>. <article-title>Low doses of ketamine and guanosine abrogate corticosterone-induced anxiety-related behavior, but not disturbances in the hippocampal NLRP3 inflammasome pathway</article-title>. <source>Psychopharmacology.</source> (<year>2021</year>) <volume>238</volume>:<fpage>2555</fpage>&#x02013;<lpage>68</lpage>. <pub-id pub-id-type="doi">10.1007/s00213-021-05879-8</pub-id><pub-id pub-id-type="pmid">34342672</pub-id></citation></ref>
<ref id="B43">
<label>43.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>H&#x000F6;rl</surname> <given-names>WH</given-names></name> <name><surname>Kittel</surname> <given-names>R</given-names></name> <name><surname>Heidland</surname> <given-names>A</given-names></name></person-group>. <article-title>Effects of high doses of leucine and ketoleucine on glycogen and protein metabolism in acute uremia</article-title>. <source>Am J Clin Nutr.</source> (<year>1980</year>) <volume>33</volume>:<fpage>1468</fpage>&#x02013;<lpage>75</lpage>. <pub-id pub-id-type="doi">10.1093/ajcn/33.7.1468</pub-id><pub-id pub-id-type="pmid">6772010</pub-id></citation></ref>
<ref id="B44">
<label>44.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Akar</surname> <given-names>E</given-names></name> <name><surname>Emon</surname> <given-names>ST</given-names></name> <name><surname>Uslu</surname> <given-names>S</given-names></name> <name><surname>Orakdogen</surname> <given-names>M</given-names></name> <name><surname>Somay</surname> <given-names>H</given-names></name></person-group>. <article-title>Effect of L-Arginine therapy on vasospasm: Experimental study in rats</article-title>. <source>World Neurosurg.</source> (<year>2019</year>) <volume>132</volume>:<fpage>e443</fpage>&#x02013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1016/j.wneu.2019.08.119</pub-id><pub-id pub-id-type="pmid">31494312</pub-id></citation></ref>
<ref id="B45">
<label>45.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Dandare</surname> <given-names>SU</given-names></name> <name><surname>Ezeonwumelu</surname> <given-names>IJ</given-names></name> <name><surname>Shinkafi</surname> <given-names>TS</given-names></name> <name><surname>Magaji</surname> <given-names>UF</given-names></name> <name><surname>Adio</surname> <given-names>AAI</given-names></name> <name><surname>Ahmad</surname> <given-names>K</given-names></name></person-group>. <article-title>L-alanine supplementation improves blood glucose level and biochemical indices in alloxan-induced diabetic rats</article-title>. <source>J Food Biochem.</source> (<year>2020</year>) <volume>45</volume>:<fpage>e13590</fpage>. <pub-id pub-id-type="doi">10.1111/jfbc.13590</pub-id><pub-id pub-id-type="pmid">33346923</pub-id></citation></ref>
<ref id="B46">
<label>46.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Schmitt</surname> <given-names>I</given-names></name> <name><surname>Kaut</surname> <given-names>O</given-names></name> <name><surname>Khazneh</surname> <given-names>H</given-names></name> <name><surname>deBoni</surname> <given-names>L</given-names></name> <name><surname>Ahmad</surname> <given-names>A</given-names></name> <name><surname>Berg</surname> <given-names>D</given-names></name> <etal/></person-group>. <article-title>L-dopa increases &#x003B1;-synuclein DNA methylation in Parkinson&#x00027;s disease patients <italic>in vivo</italic> and <italic>in vitro</italic></article-title>. <source>Movement Disord.</source> (<year>2015</year>) <volume>30</volume>:<fpage>1794</fpage>&#x02013;<lpage>801</lpage>. <pub-id pub-id-type="doi">10.1002/mds.26319</pub-id><pub-id pub-id-type="pmid">26173746</pub-id></citation></ref>
<ref id="B47">
<label>47.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Rabe</surname> <given-names>T</given-names></name> <name><surname>Przylipiak</surname> <given-names>A</given-names></name> <name><surname>Grunwald</surname> <given-names>K</given-names></name> <name><surname>Parta</surname> <given-names>S</given-names></name> <name><surname>Przylipiak</surname> <given-names>M</given-names></name> <name><surname>Runnebaum</surname> <given-names>B</given-names></name></person-group>. <article-title>Action of leukotriene B4 in human granulosa cells <italic>in vitro</italic></article-title>. <source>Hum Reprod.</source> (<year>1995</year>) <volume>10</volume>:<fpage>1881</fpage>&#x02013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1093/oxfordjournals.humrep.a136201</pub-id><pub-id pub-id-type="pmid">8583005</pub-id></citation></ref>
<ref id="B48">
<label>48.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Shao</surname> <given-names>H</given-names></name> <name><surname>Dong</surname> <given-names>L</given-names></name> <name><surname>Feng</surname> <given-names>Y</given-names></name> <name><surname>Wang</surname> <given-names>CH</given-names></name> <name><surname>Tong</surname> <given-names>HX</given-names></name></person-group>. <article-title>The protective effect of L-glutamine against acute Cantharidin-induced Cardiotoxicity in the mice</article-title>. <source>BMC Pharmacol Toxicol.</source> (<year>2020</year>) <volume>21</volume>:<fpage>71</fpage>. <pub-id pub-id-type="doi">10.1186/s40360-020-00449-8</pub-id><pub-id pub-id-type="pmid">33004081</pub-id></citation></ref>
<ref id="B49">
<label>49.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Amin</surname> <given-names>A</given-names></name> <name><surname>Frampton</surname> <given-names>J</given-names></name> <name><surname>Liu</surname> <given-names>Z</given-names></name> <name><surname>Franco-Becker</surname> <given-names>G</given-names></name> <name><surname>Norton</surname> <given-names>M</given-names></name> <name><surname>Alaa</surname> <given-names>A</given-names></name> <etal/></person-group>. <article-title>Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized crossover study</article-title>. <source>Diabetes Obes Metab.</source> (<year>2020</year>) <volume>23</volume>:<fpage>147</fpage>&#x02013;<lpage>57</lpage>. <pub-id pub-id-type="doi">10.1111/dom.14204</pub-id><pub-id pub-id-type="pmid">32991046</pub-id></citation></ref>
<ref id="B50">
<label>50.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Moradi</surname> <given-names>M</given-names></name> <name><surname>Moradi</surname> <given-names>B</given-names></name> <name><surname>Hashemian</surname> <given-names>AH</given-names></name> <name><surname>Bakhtiari</surname> <given-names>M</given-names></name> <name><surname>Khazaei</surname> <given-names>M</given-names></name> <name><surname>Esmaeili</surname> <given-names>F</given-names></name> <etal/></person-group>. <article-title>Beneficial effect of L-Proline supplementation on the quality of human spermatozoa</article-title>. <source>Andrologia.</source> (<year>2022</year>) <volume>54</volume>:<fpage>e14486</fpage>. <pub-id pub-id-type="doi">10.1111/and.14486</pub-id><pub-id pub-id-type="pmid">35716071</pub-id></citation></ref>
<ref id="B51">
<label>51.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>H</given-names></name> <name><surname>Chen</surname> <given-names>Y</given-names></name> <name><surname>Li</surname> <given-names>Y</given-names></name> <name><surname>Zhang</surname> <given-names>T</given-names></name> <name><surname>Ying</surname> <given-names>ZX</given-names></name> <name><surname>Su</surname> <given-names>WP</given-names></name> <etal/></person-group>. <article-title>l-Threonine improves intestinal mucin synthesis and immune function of intrauterine growth-retarded weanling piglets</article-title>. <source>Nutrition.</source> (<year>2018</year>) <volume>59</volume>:<fpage>182</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1016/j.nut.2018.07.114</pub-id><pub-id pub-id-type="pmid">30504005</pub-id></citation></ref>
<ref id="B52">
<label>52.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>van Zyl</surname> <given-names>LT</given-names></name> <name><surname>Chung</surname> <given-names>SA</given-names></name> <name><surname>Shahid</surname> <given-names>A</given-names></name></person-group>. <article-title>L-tryptophan as treatment for pediatric non-rapid eye movement parasomnia</article-title>. <source>J Child Adol Psychop.</source> (<year>2018</year>) <volume>28</volume>:<fpage>395</fpage>&#x02013;<lpage>401</lpage>. <pub-id pub-id-type="doi">10.1089/cap.2017.0164</pub-id><pub-id pub-id-type="pmid">29741922</pub-id></citation></ref>
<ref id="B53">
<label>53.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hung</surname> <given-names>CH</given-names></name> <name><surname>Chiu</surname> <given-names>CC</given-names></name> <name><surname>Liu</surname> <given-names>KS</given-names></name> <name><surname>Chen</surname> <given-names>YW</given-names></name> <name><surname>Wang</surname> <given-names>JJ</given-names></name></person-group>. <article-title>Subcutaneous L-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats</article-title>. <source>Eur J Pharmacol.</source> (<year>2015</year>) <volume>765</volume>:<fpage>457</fpage>&#x02013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.1016/j.ejphar.2015.09.010</pub-id><pub-id pub-id-type="pmid">26376025</pub-id></citation></ref>
<ref id="B54">
<label>54.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname> <given-names>H</given-names></name> <name><surname>Jang</surname> <given-names>JH</given-names></name> <name><surname>Kim</surname> <given-names>SJ</given-names></name></person-group>. <article-title>Malonic acid suppresses lipopolysaccharide-induced BV2 microglia cell activation by inhibiting the p38 MAPK/NF-&#x003BA;B pathway</article-title>. <source>Anim Cells Syst.</source> (<year>2021</year>) <volume>25</volume>:<fpage>110</fpage>&#x02013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1080/19768354.2021.1901781</pub-id><pub-id pub-id-type="pmid">34234892</pub-id></citation></ref>
<ref id="B55">
<label>55.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname> <given-names>X</given-names></name> <name><surname>Sun</surname> <given-names>X</given-names></name> <name><surname>Wan</surname> <given-names>X</given-names></name> <name><surname>Chen</surname> <given-names>X</given-names></name> <name><surname>Jiang</surname> <given-names>X</given-names></name></person-group>. <article-title>Mitomycin induces alveolar epithelial cell senescence by down-regulating GSK3&#x003B2; signaling</article-title>. <source>Toxicol Lett.</source> (<year>2021</year>) <volume>352</volume>:<fpage>61</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1016/j.toxlet.2021.09.015</pub-id><pub-id pub-id-type="pmid">34624459</pub-id></citation></ref>
<ref id="B56">
<label>56.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kuwahara</surname> <given-names>M</given-names></name> <name><surname>Ito</surname> <given-names>K</given-names></name> <name><surname>Hayakawa</surname> <given-names>K</given-names></name> <name><surname>Yagi</surname> <given-names>S</given-names></name> <name><surname>Shiota</surname> <given-names>K</given-names></name></person-group>. <article-title>N-Acetylmannosamine improves sleep-wake quality in middle-aged mice: Relevance to autonomic nervous function</article-title>. <source>Auton Neurosci-Basic.</source> (<year>2014</year>) <volume>187</volume>:<fpage>56</fpage>&#x02013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.1016/j.autneu.2014.11.005</pub-id><pub-id pub-id-type="pmid">25443216</pub-id></citation></ref>
<ref id="B57">
<label>57.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hwang</surname> <given-names>J</given-names></name> <name><surname>Kim</surname> <given-names>YR</given-names></name> <name><surname>Park</surname> <given-names>JY</given-names></name> <name><surname>Nam</surname> <given-names>WH</given-names></name> <name><surname>Kim</surname> <given-names>J</given-names></name> <name><surname>Cho</surname> <given-names>J</given-names></name> <etal/></person-group>. <article-title>Selective anticancer materials by self-assembly of synthetic amphiphiles based on N-Acetylneuraminic acid</article-title>. <source>ACS Appl Mater Inter.</source> (<year>2022</year>) <volume>14</volume>:<fpage>16100</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1021/acsami.2c02922</pub-id><pub-id pub-id-type="pmid">35377593</pub-id></citation></ref>
<ref id="B58">
<label>58.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cook</surname> <given-names>TM</given-names></name> <name><surname>Brown</surname> <given-names>KG</given-names></name> <name><surname>Boyle</surname> <given-names>JV</given-names></name> <name><surname>Goss</surname> <given-names>WA</given-names></name></person-group>. <article-title>Bactericidal action of nalidixic acid on <italic>Bacillus subtilis</italic></article-title>. <source>J Bacteriol</source>. (<year>1966</year>) <volume>92</volume>:<fpage>1510</fpage>&#x02013;<lpage>4</lpage>. <pub-id pub-id-type="doi">10.1128/jb.92.5.1510-1514.1966</pub-id><pub-id pub-id-type="pmid">4958883</pub-id></citation></ref>
<ref id="B59">
<label>59.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Blanchard</surname> <given-names>C</given-names></name> <name><surname>Brooks</surname> <given-names>L</given-names></name> <name><surname>Beckley</surname> <given-names>A</given-names></name> <name><surname>Colquhoun</surname> <given-names>J</given-names></name> <name><surname>Dewhurst</surname> <given-names>S</given-names></name></person-group>. <article-title>Neomycin sulfate improves the antimicrobial activity of mupirocin-based antibacterial ointments</article-title>. <source>Antimicrob Agents Ch.</source> (<year>2015</year>) <volume>60</volume>:<fpage>862</fpage>&#x02013;<lpage>72</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.02083-15</pub-id><pub-id pub-id-type="pmid">26596945</pub-id></citation></ref>
<ref id="B60">
<label>60.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Levy</surname> <given-names>B</given-names></name> <name><surname>Clere-Jehl</surname> <given-names>R</given-names></name> <name><surname>Legras</surname> <given-names>A</given-names></name> <name><surname>Morichau-Beauchant</surname> <given-names>T</given-names></name> <name><surname>Leone</surname> <given-names>M</given-names></name> <name><surname>Frederique</surname> <given-names>G</given-names></name> <etal/></person-group>. <article-title>Epinephrine versus norepinephrine for cardiogenic shock after acute myocardial infarction</article-title>. <source>J Am Coll Cardiol.</source> (<year>2018</year>) <volume>72</volume>:<fpage>173</fpage>&#x02013;<lpage>82</lpage>. <pub-id pub-id-type="doi">10.1016/j.jacc.2018.04.051</pub-id><pub-id pub-id-type="pmid">30384901</pub-id></citation></ref>
<ref id="B61">
<label>61.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Valvassori</surname> <given-names>SS</given-names></name> <name><surname>Dal-Pont</surname> <given-names>GC</given-names></name> <name><surname>Varela</surname> <given-names>RB</given-names></name> <name><surname>Resende</surname> <given-names>WR</given-names></name> <name><surname>Quevedo</surname> <given-names>J</given-names></name></person-group>. <article-title>Ouabain induces memory impairment and alter the BDNF signaling pathway in an animal model of bipolar disorder: Cognitive and neurochemical alterations in BD model</article-title>. <source>J Affect Disord.</source> (<year>2020</year>) <volume>282</volume>:<fpage>1195</fpage>&#x02013;<lpage>202</lpage>. <pub-id pub-id-type="doi">10.1016/j.jad.2020.12.190</pub-id><pub-id pub-id-type="pmid">33601696</pub-id></citation></ref>
<ref id="B62">
<label>62.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Callegari</surname> <given-names>EA</given-names></name> <name><surname>Ferguson-Gottschall</surname> <given-names>S</given-names></name> <name><surname>Gibori</surname> <given-names>G</given-names></name></person-group>. <article-title>PGF2alpha induced differential expression of genes involved in turnover of extracellular matrix in rat decidual cells</article-title>. <source>Reprod Biol Endocrinol.</source> (<year>2005</year>) <volume>3</volume>:<fpage>3</fpage>. <pub-id pub-id-type="doi">10.1186/1477-7827-3-3</pub-id><pub-id pub-id-type="pmid">15644143</pub-id></citation></ref>
<ref id="B63">
<label>63.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zheng</surname> <given-names>Y</given-names></name> <name><surname>Martin-Morales</surname> <given-names>A</given-names></name> <name><surname>Wang</surname> <given-names>J</given-names></name> <name><surname>Fujishima</surname> <given-names>M</given-names></name> <name><surname>Okumura</surname> <given-names>E</given-names></name> <name><surname>Sato</surname> <given-names>K</given-names></name></person-group>. <article-title>Phenethylamine in chlorella alleviates high-fat diet-induced mouse liver damage by regulating generation of methylglyoxal</article-title>. <source>NPJ Sci Food.</source> (<year>2021</year>) <volume>5</volume>:<fpage>22</fpage>. <pub-id pub-id-type="doi">10.1038/s41538-021-00105-3</pub-id><pub-id pub-id-type="pmid">34301957</pub-id></citation></ref>
<ref id="B64">
<label>64.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Negintaji</surname> <given-names>K</given-names></name> <name><surname>Ghanbari</surname> <given-names>A</given-names></name> <name><surname>Frozanfar</surname> <given-names>M</given-names></name> <name><surname>Jafarinia</surname> <given-names>M</given-names></name> <name><surname>Zibara</surname> <given-names>K</given-names></name></person-group>. <article-title>Pregnenolone enhances the proliferation of mouse neural stem cells and promotes oligodendrogenesis, together with Sox10, and neurogenesis, along with Notch1 and Pax6</article-title>. <source>Neurochem Int.</source> (<year>2023</year>) <volume>163</volume>:<fpage>105489</fpage>. <pub-id pub-id-type="doi">10.1016/j.neuint.2023.105489</pub-id><pub-id pub-id-type="pmid">36657722</pub-id></citation></ref>
<ref id="B65">
<label>65.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Toppozada</surname> <given-names>MK</given-names></name> <name><surname>Darwish</surname> <given-names>E</given-names></name> <name><surname>Barakat</surname> <given-names>AA</given-names></name></person-group>. <article-title>Management of severe preeclampsia detected in early labor by prostaglandin A1 or dihydralazine infusions</article-title>. <source>Am J Obstet Gynecol.</source> (<year>1991</year>) <volume>164</volume>:<fpage>1229</fpage>&#x02013;<lpage>32</lpage>. <pub-id pub-id-type="doi">10.1016/0002-9378(91)90688-N</pub-id><pub-id pub-id-type="pmid">2035562</pub-id></citation></ref>
<ref id="B66">
<label>66.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Honma</surname> <given-names>Y</given-names></name> <name><surname>Arai</surname> <given-names>I</given-names></name> <name><surname>Hashimoto</surname> <given-names>Y</given-names></name> <name><surname>Futaki</surname> <given-names>N</given-names></name> <name><surname>Sugimoto</surname> <given-names>M</given-names></name> <name><surname>Tanaka</surname> <given-names>M</given-names></name> <etal/></person-group>. <article-title>Prostaglandin D2 and prostaglandin E2 accelerate the recovery of cutaneous barrier disruption induced by mechanical scratching in mice</article-title>. <source>Eur J Pharmacol.</source> (<year>2005</year>) <volume>518</volume>:<fpage>56</fpage>&#x02013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.1016/j.ejphar.2005.06.006</pub-id><pub-id pub-id-type="pmid">16000196</pub-id></citation></ref>
<ref id="B67">
<label>67.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Najafpour</surname> <given-names>A</given-names></name> <name><surname>Mohammadi</surname> <given-names>R</given-names></name> <name><surname>Faraji</surname> <given-names>D</given-names></name> <name><surname>Amini</surname> <given-names>K</given-names></name></person-group>. <article-title>Local administration of prostaglandin E1 combined with silicone chamber improves peripheral nerve regeneration</article-title>. <source>Int J Surg.</source> (<year>2013</year>) <volume>11</volume>:<fpage>1010</fpage>&#x02013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijsu.2013.05.034</pub-id><pub-id pub-id-type="pmid">23747978</pub-id></citation></ref>
<ref id="B68">
<label>68.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Salera</surname> <given-names>D</given-names></name> <name><surname>Argalia</surname> <given-names>G</given-names></name> <name><surname>Giuseppetti</surname> <given-names>GM</given-names></name></person-group>. <article-title>Hemodynamic effects of a prostacyclin analog (Prostavasin) in systemic scleroderma patients</article-title>. <source>Radiol Med.</source> (<year>2005</year>) <volume>110</volume>:<fpage>106</fpage>&#x02013;<lpage>14</lpage>.<pub-id pub-id-type="pmid">16163145</pub-id></citation></ref>
<ref id="B69">
<label>69.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mahmoud</surname> <given-names>A</given-names></name> <name><surname>Tabassum</surname> <given-names>S</given-names></name> <name><surname>Al Enazi</surname> <given-names>S</given-names></name> <name><surname>Lubbad</surname> <given-names>N</given-names></name> <name><surname>Benini</surname> <given-names>R</given-names></name></person-group>. <article-title>Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study</article-title>. <source>Pediatr Neurol</source>. (<year>2021</year>) <volume>119</volume>:<fpage>15</fpage>&#x02013;<lpage>21</lpage>. <pub-id pub-id-type="doi">10.1016/j.pediatrneurol.2021.02.010</pub-id><pub-id pub-id-type="pmid">33823377</pub-id></citation></ref>
<ref id="B70">
<label>70.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Das</surname> <given-names>R</given-names></name> <name><surname>Qubty</surname> <given-names>W</given-names></name></person-group>. <article-title>Retrospective observational study on riboflavin prophylaxis in child and adolescent migraine</article-title>. <source>Pediatr Neurol.</source> (<year>2020</year>) <volume>114</volume>:<fpage>5</fpage>&#x02013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1016/j.pediatrneurol.2020.09.009</pub-id><pub-id pub-id-type="pmid">33189027</pub-id></citation></ref>
<ref id="B71">
<label>71.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Beauchamp</surname> <given-names>LC</given-names></name> <name><surname>Liu</surname> <given-names>XM</given-names></name> <name><surname>Sedjahtera</surname> <given-names>A</given-names></name> <name><surname>Bogeski</surname> <given-names>M</given-names></name> <name><surname>Vella</surname> <given-names>LJ</given-names></name> <name><surname>Bush</surname> <given-names>AI</given-names></name> <etal/></person-group>. <article-title>S-Adenosylmethionine rescues cognitive deficits in the rTg4510 animal model by stabilizing protein phosphatase 2A and reducing phosphorylated Tau</article-title>. <source>J Alzheimers Dis.</source> (<year>2020</year>) <volume>77</volume>:<fpage>1705</fpage>&#x02013;<lpage>15</lpage>. <pub-id pub-id-type="doi">10.3233/JAD-200756</pub-id><pub-id pub-id-type="pmid">32925070</pub-id></citation></ref>
<ref id="B72">
<label>72.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Diniz</surname> <given-names>DA</given-names></name> <name><surname>Petrocchi</surname> <given-names>JA</given-names></name> <name><surname>Navarro</surname> <given-names>LC</given-names></name> <name><surname>Souza</surname> <given-names>TC</given-names></name> <name><surname>Castor</surname> <given-names>MGME</given-names></name> <name><surname>Duarte</surname> <given-names>IDG</given-names></name> <etal/></person-group>. <article-title>Serotonin induces peripheral antinociception via the opioidergic system</article-title>. <source>Biomed Pharmacother.</source> (<year>2017</year>) <volume>97</volume>:<fpage>1434</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1016/j.biopha.2017.11.048</pub-id><pub-id pub-id-type="pmid">29156533</pub-id></citation></ref>
<ref id="B73">
<label>73.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gao</surname> <given-names>HX</given-names></name> <name><surname>Gao</surname> <given-names>HJ</given-names></name> <name><surname>Xu</surname> <given-names>GH</given-names></name> <name><surname>Li</surname> <given-names>M</given-names></name> <name><surname>Du</surname> <given-names>SZ</given-names></name> <name><surname>Li</surname> <given-names>F</given-names></name> <etal/></person-group>. <article-title>Efficacy and safety of repeated oral sucrose for repeated procedural pain in neonates: A systematic review</article-title>. <source>Int J Nurs Stud.</source> (<year>2016</year>) <volume>62</volume>:<fpage>118</fpage>&#x02013;<lpage>25</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijnurstu.2016.07.015</pub-id><pub-id pub-id-type="pmid">27474944</pub-id></citation></ref>
<ref id="B74">
<label>74.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Guerrero</surname> <given-names>JG</given-names></name> <name><surname>Ishida</surname> <given-names>E</given-names></name> <name><surname>Shibusawa</surname> <given-names>N</given-names></name> <name><surname>Lei</surname> <given-names>X</given-names></name> <name><surname>Yamada</surname> <given-names>S</given-names></name> <name><surname>Horiguchi</surname> <given-names>K</given-names></name> <etal/></person-group>. <article-title>Role of thyrotropin-releasing hormone in regulating fibroblast growth factor 21 in mouse pancreatic &#x003B2; Cells</article-title>. <source>Thyroid.</source> (<year>2023</year>) <volume>33</volume>:<fpage>251</fpage>&#x02013;<lpage>60</lpage>. <pub-id pub-id-type="doi">10.1089/thy.2022.0144</pub-id><pub-id pub-id-type="pmid">36333931</pub-id></citation></ref>
<ref id="B75">
<label>75.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yan</surname> <given-names>ZY</given-names></name> <name><surname>Zhao</surname> <given-names>MR</given-names></name> <name><surname>Huang</surname> <given-names>CY</given-names></name> <name><surname>Zhang</surname> <given-names>LJ</given-names></name> <name><surname>Zhang</surname> <given-names>JX</given-names></name></person-group>. <article-title>Trehalose alleviates high-temperature stress in <italic>Pleurotus ostreatus</italic> by affecting central carbon metabolism</article-title>. <source>Microb Cell Fact.</source> (<year>2021</year>) <volume>20</volume>:<fpage>82</fpage>. <pub-id pub-id-type="doi">10.1186/s12934-021-01572-9</pub-id><pub-id pub-id-type="pmid">33827585</pub-id></citation></ref>
<ref id="B76">
<label>76.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ramesh</surname> <given-names>D</given-names></name> <name><surname>Vijayakumar</surname> <given-names>BG</given-names></name> <name><surname>Kannan</surname> <given-names>T</given-names></name></person-group>. <article-title>Therapeutic potential of uracil and its derivatives in countering pathogenic and physiological disorders</article-title>. <source>Eur J Med Chem</source>. (<year>2020</year>) <volume>207</volume>:<fpage>112801</fpage>. <pub-id pub-id-type="doi">10.1016/j.ejmech.2020.112801</pub-id><pub-id pub-id-type="pmid">32927231</pub-id></citation></ref>
<ref id="B77">
<label>77.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Al</surname> <given-names>N</given-names></name> <name><surname>&#x000C7;akir</surname> <given-names>A</given-names></name> <name><surname>Ko&#x000E7;</surname> <given-names>C</given-names></name> <name><surname>Cansev</surname> <given-names>M</given-names></name> <name><surname>Alkan</surname> <given-names>T</given-names></name></person-group>. <article-title>Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury</article-title>. <source>Turk J Med Sci.</source> (<year>2020</year>) <volume>50</volume>:<fpage>2059</fpage>&#x02013;<lpage>66</lpage>. <pub-id pub-id-type="doi">10.3906/sag-2002-14</pub-id><pub-id pub-id-type="pmid">32490647</pub-id></citation></ref>
<ref id="B78">
<label>78.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Su</surname> <given-names>HL</given-names></name> <name><surname>Chen</surname> <given-names>JY</given-names></name> <name><surname>Huang</surname> <given-names>YZ</given-names></name></person-group>. <article-title>Quantitative analysis of amino acids in different areas of <italic>Mesona Chinensis</italic></article-title>. In: <source>Proceedings and Abstracts of the 9th National Symposium on Natural Medicinal Material Resources</source>. Guangzhou; Huazhou (<year>2010</year>). p. <fpage>523</fpage>&#x02013;<lpage>6</lpage>.</citation>
</ref>
<ref id="B79">
<label>79.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Aarthi</surname> <given-names>R</given-names></name> <name><surname>Saranya</surname> <given-names>R</given-names></name> <name><surname>Sankaran</surname> <given-names>K</given-names></name></person-group>. <article-title>2-methylbutanal, a volatile biomarker, for non-invasive surveillance of Proteus</article-title>. <source>Appl Microbiol Biotechnol.</source> (<year>2013</year>) <volume>98</volume>:<fpage>445</fpage>&#x02013;<lpage>54</lpage>. <pub-id pub-id-type="doi">10.1007/s00253-013-5393-9</pub-id><pub-id pub-id-type="pmid">24281757</pub-id></citation></ref>
<ref id="B80">
<label>80.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ito</surname> <given-names>K</given-names></name> <name><surname>Ito</surname> <given-names>M</given-names></name></person-group>. <article-title>The sedative effect of inhaled terpinolene in mice and its structure-activity relationships</article-title>. <source>J Nat Med.</source> (<year>2013</year>) <volume>67</volume>:<fpage>833</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1007/s11418-012-0732-1</pub-id><pub-id pub-id-type="pmid">23339024</pub-id></citation></ref>
<ref id="B81">
<label>81.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kaur</surname> <given-names>K</given-names></name> <name><surname>Kaur</surname> <given-names>G</given-names></name> <name><surname>Brar</surname> <given-names>JS</given-names></name></person-group>. <article-title>Pre-harvest application of hexanal formulations for improving post-harvest life and quality of mango (<italic>Mangifera indica</italic> L) cv Dashehari</article-title>. <source>J Food Sci Technol.</source> (<year>2020</year>) <volume>57</volume>:<fpage>4257</fpage>&#x02013;<lpage>64</lpage>. <pub-id pub-id-type="doi">10.1007/s13197-020-04464-9</pub-id><pub-id pub-id-type="pmid">33071347</pub-id></citation></ref>
<ref id="B82">
<label>82.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yamada</surname> <given-names>K</given-names></name> <name><surname>Sano</surname> <given-names>M</given-names></name> <name><surname>Fujihara</surname> <given-names>H</given-names></name> <name><surname>Ohta</surname> <given-names>A</given-names></name></person-group>. <article-title>Effect of 2,5-dimethylpyrazine on uterine contraction in late stage of pregnant female rats</article-title>. <source>Biol Pharm Bull.</source> (<year>2003</year>) <volume>26</volume>:<fpage>1614</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1248/bpb.26.1614</pub-id><pub-id pub-id-type="pmid">14600412</pub-id></citation></ref>
<ref id="B83">
<label>83.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ashigai</surname> <given-names>H</given-names></name> <name><surname>Ikeshima</surname> <given-names>E</given-names></name> <name><surname>Koizumi</surname> <given-names>K</given-names></name> <name><surname>Nakashima</surname> <given-names>K</given-names></name> <name><surname>Mizutani</surname> <given-names>M</given-names></name> <name><surname>Yajima</surname> <given-names>H</given-names></name></person-group>. <article-title>2-Ethylpyrazine induces vasodilatation by releasing nitric oxide in the <italic>Endothelium</italic></article-title>. <source>Biol Pharm Bull</source>. (<year>2017</year>) <volume>40</volume>:<fpage>2153</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1248/bpb.b17-00551</pub-id><pub-id pub-id-type="pmid">28966226</pub-id></citation></ref>
<ref id="B84">
<label>84.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Han</surname> <given-names>R</given-names></name> <name><surname>Nusbaum</surname> <given-names>O</given-names></name> <name><surname>Chen</surname> <given-names>X</given-names></name> <name><surname>Zhu</surname> <given-names>Y</given-names></name></person-group>. <article-title>Valeric acid suppresses liver cancer development by acting as a novel HDAC inhibitor</article-title>. <source>Mol Ther Oncolytics.</source> (<year>2020</year>) <volume>19</volume>:<fpage>8</fpage>&#x02013;<lpage>18</lpage>. <pub-id pub-id-type="doi">10.1016/j.omto.2020.08.017</pub-id><pub-id pub-id-type="pmid">33024815</pub-id></citation></ref>
<ref id="B85">
<label>85.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Majdabadi</surname> <given-names>N</given-names></name> <name><surname>Falahati</surname> <given-names>M</given-names></name> <name><surname>Heidarie-Kohan</surname> <given-names>F</given-names></name> <name><surname>Farahyar</surname> <given-names>S</given-names></name> <name><surname>Rahimi-Moghaddam</surname> <given-names>P</given-names></name> <name><surname>Ashrafi-Khozani</surname> <given-names>M</given-names></name> <etal/></person-group>. <article-title>Effect of 2-Phenylethanol as antifungal agent and common antifungals (Amphotericin B, Fluconazole, and Itraconazole) on candida ppecies isolated from chronic and recurrent cases of <italic>Candidal Vulvovaginitis</italic></article-title>. <source>ASSAY Drug Dev Techn</source>. (<year>2018</year>) <volume>16</volume>:<fpage>141</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1089/adt.2017.837</pub-id><pub-id pub-id-type="pmid">29658789</pub-id></citation></ref>
<ref id="B86">
<label>86.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Vazquez-Jimenez</surname> <given-names>JG</given-names></name> <name><surname>Chavez-Reyes</surname> <given-names>J</given-names></name> <name><surname>Romero-Garcia</surname> <given-names>T</given-names></name> <name><surname>Zarain-Herzberg</surname> <given-names>A</given-names></name> <name><surname>Valdes-Flores</surname> <given-names>J</given-names></name> <name><surname>Galindo-Rosales</surname> <given-names>JM</given-names></name> <etal/></person-group>. <article-title>Palmitic acid but not palmitoleic acid induces insulin resistance in a human endothelial cell line by decreasing SERCA pump expression</article-title>. <source>Cell Signal.</source> (<year>2015</year>) <volume>28</volume>:<fpage>53</fpage>&#x02013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1016/j.cellsig.2015.10.001</pub-id><pub-id pub-id-type="pmid">26475209</pub-id></citation></ref>
<ref id="B87">
<label>87.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhao</surname> <given-names>ZG</given-names></name> <name><surname>Shi</surname> <given-names>YP</given-names></name> <name><surname>Huang</surname> <given-names>NZ</given-names></name> <name><surname>Fu</surname> <given-names>CM</given-names></name> <name><surname>Tang</surname> <given-names>FL</given-names></name> <name><surname>Jiang</surname> <given-names>QY</given-names></name></person-group>. <article-title>The research advances on <italic>Mesona chinensis</italic> Benth in China</article-title>. <source>J Southern Agri.</source> (<year>2011</year>) <volume>42</volume>:<fpage>657</fpage>&#x02013;<lpage>60</lpage>. <pub-id pub-id-type="doi">10.16213/j.cnki.scjas.2011.04.036</pub-id><pub-id pub-id-type="pmid">24708679</pub-id></citation></ref>
<ref id="B88">
<label>88.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>WB</given-names></name> <name><surname>Wang</surname> <given-names>ZC</given-names></name> <name><surname>Zhang</surname> <given-names>LY</given-names></name> <name><surname>Qian</surname> <given-names>JH</given-names></name></person-group>. <article-title>Analysis of monosaccharide composition and content in <italic>Mesona Chinensis</italic> Benth polysaccharides by precolumn derivatization ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry</article-title>. <source>J Instrument Anal.</source> (<year>2013</year>) <volume>32</volume>:<fpage>143</fpage>&#x02013;<lpage>9</lpage>.</citation>
</ref>
<ref id="B89">
<label>89.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname> <given-names>XG</given-names></name> <name><surname>Chen</surname> <given-names>MM</given-names></name></person-group>. <article-title>Research on the exploitation and utilization of <italic>Mesona blume</italic> in China</article-title>. <source>Food Res Dev.</source> (<year>2004</year>) <volume>5</volume>:<fpage>109</fpage>&#x02013;<lpage>14</lpage>. <pub-id pub-id-type="doi">10.3969/j.issn.1005-6521.2004.05.040</pub-id></citation>
</ref>
<ref id="B90">
<label>90.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname> <given-names>LS</given-names></name> <name><surname>Gu</surname> <given-names>YF</given-names></name> <name><surname>Li</surname> <given-names>H</given-names></name></person-group>. <article-title>Advances in herbal volatile oil and aromatic herbs</article-title>. <source>China J Chin Materia Medica.</source> (<year>2009</year>) <volume>34</volume>:<fpage>1605</fpage>&#x02013;<lpage>11</lpage>.<pub-id pub-id-type="pmid">19777853</pub-id></citation></ref>
<ref id="B91">
<label>91.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname> <given-names>MF</given-names></name> <name><surname>Tang</surname> <given-names>Y</given-names></name> <name><surname>Zheng</surname> <given-names>Q</given-names></name> <name><surname>Tang</surname> <given-names>DF</given-names></name> <name><surname>Luo</surname> <given-names>J</given-names></name> <name><surname>Hu</surname> <given-names>PY</given-names></name> <etal/></person-group>. <article-title>Effects of different extraction methods on composition and antibacterial activity of volatile oil from <italic>Forsythiae Fructus, Schinzonepetae Herba</italic>, and <italic>Menthae Haplocalycis</italic> Herba</article-title>. <source>Chin Trad Herbal Drugs.</source> (<year>2018</year>) <volume>49</volume>:<fpage>2845</fpage>&#x02013;<lpage>54</lpage>. <pub-id pub-id-type="doi">10.7501/j.issn.0253-2670.2018.12.017</pub-id></citation>
</ref>
<ref id="B92">
<label>92.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Li</surname> <given-names>SM</given-names></name> <name><surname>Zeng</surname> <given-names>BY</given-names></name> <name><surname>Ye</surname> <given-names>Q</given-names></name> <name><surname>Ao</surname> <given-names>H</given-names></name> <name><surname>Li</surname> <given-names>HX</given-names></name></person-group>. <article-title>Correlation analysis between GC-MS fingerprint of essential oil of <italic>Amomi Fructus</italic> and anti-inflammatory activity</article-title>. <source>Chin J Exp Trad Med Formulae.</source> (<year>2015</year>) <volume>21</volume>:<fpage>133</fpage>&#x02013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.13422/j.cnki.syfjx.2015090133</pub-id></citation>
</ref>
<ref id="B93">
<label>93.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Han</surname> <given-names>F</given-names></name> <name><surname>Zeng</surname> <given-names>L</given-names></name> <name><surname>Wu</surname> <given-names>ZF</given-names></name> <name><surname>Shu</surname> <given-names>JC</given-names></name> <name><surname>Zhao</surname> <given-names>ZD</given-names></name> <name><surname>Xiong</surname> <given-names>W</given-names></name> <etal/></person-group>. <article-title>Analysis of the application and current situation of anti-tumor Chinese medicine volatile oils by searching &#x0201C;The compilation of Chinese Medicine Standard&#x0201D; database</article-title>. <source>Chin Pharmaceut J.</source> (<year>2017</year>) <volume>15</volume>:<fpage>1376</fpage>&#x02013;<lpage>80</lpage>. <pub-id pub-id-type="doi">10.11669/cpj.2017.15.019</pub-id></citation>
</ref>
<ref id="B94">
<label>94.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname> <given-names>CH</given-names></name> <name><surname>Wei</surname> <given-names>J</given-names></name></person-group>. <article-title>Comparative analysis of the volatile aroma compounds of <italic>Mesona Benth</italic> in the different regions</article-title>. <source>Modern Food.</source> (<year>2016</year>) <volume>11</volume>:<fpage>1</fpage>&#x02013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.16736/j.cnki.cn41-1434/ts.2016.11.001</pub-id></citation>
</ref>
<ref id="B95">
<label>95.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wei</surname> <given-names>J</given-names></name> <name><surname>Zheng</surname> <given-names>EL</given-names></name> <name><surname>Cai</surname> <given-names>XK</given-names></name> <name><surname>Ji</surname> <given-names>XD</given-names></name> <name><surname>Xu</surname> <given-names>CH</given-names></name></person-group>. <article-title>Preparation of water-soluble extracts from <italic>Mesona Benth</italic> and analysis of the volatile aroma components by GC-MS</article-title>. <source>Food Sci Technol.</source> (<year>2014</year>) <volume>39</volume>:<fpage>190</fpage>&#x02013;<lpage>2</lpage>. <pub-id pub-id-type="doi">10.13684/j.cnki.spkj.2014.05.044</pub-id></citation>
</ref>
<ref id="B96">
<label>96.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname> <given-names>FL</given-names></name> <name><surname>Xin</surname> <given-names>XF</given-names></name> <name><surname>Tang</surname> <given-names>QF</given-names></name></person-group>. <article-title>Extraction and GC-MS analysis of essential oil from <italic>Mesona chinensis</italic> Benth by Supercritical CO<sub>2</sub> extraction and hydrodistillation methods</article-title>. <source>J Chin Med Mater.</source> (<year>2012</year>) <volume>8</volume>:<fpage>1270</fpage>&#x02013;<lpage>3</lpage>.</citation>
</ref>
<ref id="B97">
<label>97.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kung</surname> <given-names>TL</given-names></name> <name><surname>Chen</surname> <given-names>YJ</given-names></name> <name><surname>Chao</surname> <given-names>LK</given-names></name> <name><surname>Wu</surname> <given-names>CS</given-names></name> <name><surname>Lin</surname> <given-names>LY</given-names></name> <name><surname>Chen</surname> <given-names>HC</given-names></name></person-group>. <article-title>Analysis of volatile constituents in <italic>Platostoma palustre</italic> (Blume) using headspace solid-phase microextraction and simultaneous distillation-extraction</article-title>. <source>Foods.</source> (<year>2019</year>) <volume>8</volume>:<fpage>415</fpage>. <pub-id pub-id-type="doi">10.3390/foods8090415</pub-id><pub-id pub-id-type="pmid">31540084</pub-id></citation></ref>
<ref id="B98">
<label>98.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Deng</surname> <given-names>C</given-names></name> <name><surname>Li</surname> <given-names>RM</given-names></name></person-group>. <article-title>Analysis of the chemical constituents of the essential oils from <italic>Mesona chinensis</italic> benth by gas chromatography-mass spectrometry</article-title>. <source>China Modern Med.</source> (<year>2012</year>) <volume>19</volume>:<fpage>68</fpage>&#x02013;<lpage>9</lpage>. </citation>
</ref>
</ref-list> 
</back>
</article> 