Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression

This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:International journal of biological sciences 2022-01, Vol.18 (12), p.4618-4628
Hauptverfasser: Xue, Mingshan, Zhang, Teng, Cheng, Zhangkai J., Guo, Baojun, Zeng, Yifeng, Lin, Runpei, Zheng, Peiyan, Liu, Mingtao, Hu, Fengyu, Li, Feng, Zhang, Wensheng, Li, Lu, Zhao, Qi, Sun, Baoqing, Tang, Xiaoping
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 4628
container_issue 12
container_start_page 4618
container_title International journal of biological sciences
container_volume 18
creator Xue, Mingshan
Zhang, Teng
Cheng, Zhangkai J.
Guo, Baojun
Zeng, Yifeng
Lin, Runpei
Zheng, Peiyan
Liu, Mingtao
Hu, Fengyu
Li, Feng
Zhang, Wensheng
Li, Lu
Zhao, Qi
Sun, Baoqing
Tang, Xiaoping
description This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P< 0.05) between patients and healthy controls (P< 0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.
doi_str_mv 10.7150/ijbs.72450
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9305269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2694417509</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3343-d63c6c23e48e5ffcce95a2541c1d02c9eeb40d567ab5cde1f21bf394b69b716a3</originalsourceid><addsrcrecordid>eNpdkV1r1UAQhhdRbK3e-AsWvBEhdT-T7I1QTlsttPRcVG-XzWa22UOSPe4kltI_b9IWUa9mYJ55GOYl5D1nxxXX7HPcNXhcCaXZC3LIlTKFEHX98q_-gLxB3DEmS12z1-RA6rpSRqlD8nAWAviJpkAdPZ9HP8U0up5uu4T7LvVxH1t6BZNrUp8GKLY5TRBHeoKYfHQrTbdu6u7cPV3aqYOF9p0bIw6rdHP94-K04IaeRgSHQBfBbQbEZfEteRVcj_DuuR6R7-dnN5tvxeX114vNyWXhpVSyaEvpSy8kqBp0CN6D0U5oxT1vmfAGoFGs1WXlGu1b4EHwJkijmtI0FS-dPCJfnrz7uRmg9TBO2fV2n-Pg8r1NLtp_J2Ps7G36ZY1kWpRmEXx8FuT0cwac7BDRQ9-7EdKMdmGU4pVmK_rhP3SX5rx89JFilRS6Egv16YnyOSFmCH-O4cyumdo1U_uYqfwNAPiVGQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2690732572</pqid></control><display><type>article</type><title>Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>PubMed Central</source><creator>Xue, Mingshan ; Zhang, Teng ; Cheng, Zhangkai J. ; Guo, Baojun ; Zeng, Yifeng ; Lin, Runpei ; Zheng, Peiyan ; Liu, Mingtao ; Hu, Fengyu ; Li, Feng ; Zhang, Wensheng ; Li, Lu ; Zhao, Qi ; Sun, Baoqing ; Tang, Xiaoping</creator><creatorcontrib>Xue, Mingshan ; Zhang, Teng ; Cheng, Zhangkai J. ; Guo, Baojun ; Zeng, Yifeng ; Lin, Runpei ; Zheng, Peiyan ; Liu, Mingtao ; Hu, Fengyu ; Li, Feng ; Zhang, Wensheng ; Li, Lu ; Zhao, Qi ; Sun, Baoqing ; Tang, Xiaoping</creatorcontrib><description>This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P&lt; 0.05) between patients and healthy controls (P&lt; 0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.</description><identifier>ISSN: 1449-2288</identifier><identifier>EISSN: 1449-2288</identifier><identifier>DOI: 10.7150/ijbs.72450</identifier><identifier>PMID: 35874944</identifier><language>eng</language><publisher>Sydney: Ivyspring International Publisher Pty Ltd</publisher><subject>Acids ; Blood diseases ; Ceramide ; Coronaviruses ; COVID-19 ; Discriminant analysis ; Fibrin ; Inflammation ; Kidneys ; Lecithin ; Lipopolysaccharides ; Mass spectrometry ; Metabolic pathways ; Metabolism ; Metabolites ; Metabolomics ; Patients ; Phosphatidylcholine ; Phosphatidylinositol ; Phospholipids ; Plasma ; Proteins ; Proteomics ; Research Paper ; Scientific imaging ; Severe acute respiratory syndrome coronavirus 2 ; Signal transduction ; Variables ; Vortices</subject><ispartof>International journal of biological sciences, 2022-01, Vol.18 (12), p.4618-4628</ispartof><rights>2022. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3343-d63c6c23e48e5ffcce95a2541c1d02c9eeb40d567ab5cde1f21bf394b69b716a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305269/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305269/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids></links><search><creatorcontrib>Xue, Mingshan</creatorcontrib><creatorcontrib>Zhang, Teng</creatorcontrib><creatorcontrib>Cheng, Zhangkai J.</creatorcontrib><creatorcontrib>Guo, Baojun</creatorcontrib><creatorcontrib>Zeng, Yifeng</creatorcontrib><creatorcontrib>Lin, Runpei</creatorcontrib><creatorcontrib>Zheng, Peiyan</creatorcontrib><creatorcontrib>Liu, Mingtao</creatorcontrib><creatorcontrib>Hu, Fengyu</creatorcontrib><creatorcontrib>Li, Feng</creatorcontrib><creatorcontrib>Zhang, Wensheng</creatorcontrib><creatorcontrib>Li, Lu</creatorcontrib><creatorcontrib>Zhao, Qi</creatorcontrib><creatorcontrib>Sun, Baoqing</creatorcontrib><creatorcontrib>Tang, Xiaoping</creatorcontrib><title>Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression</title><title>International journal of biological sciences</title><description>This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P&lt; 0.05) between patients and healthy controls (P&lt; 0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.</description><subject>Acids</subject><subject>Blood diseases</subject><subject>Ceramide</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Discriminant analysis</subject><subject>Fibrin</subject><subject>Inflammation</subject><subject>Kidneys</subject><subject>Lecithin</subject><subject>Lipopolysaccharides</subject><subject>Mass spectrometry</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Patients</subject><subject>Phosphatidylcholine</subject><subject>Phosphatidylinositol</subject><subject>Phospholipids</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Research Paper</subject><subject>Scientific imaging</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Signal transduction</subject><subject>Variables</subject><subject>Vortices</subject><issn>1449-2288</issn><issn>1449-2288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkV1r1UAQhhdRbK3e-AsWvBEhdT-T7I1QTlsttPRcVG-XzWa22UOSPe4kltI_b9IWUa9mYJ55GOYl5D1nxxXX7HPcNXhcCaXZC3LIlTKFEHX98q_-gLxB3DEmS12z1-RA6rpSRqlD8nAWAviJpkAdPZ9HP8U0up5uu4T7LvVxH1t6BZNrUp8GKLY5TRBHeoKYfHQrTbdu6u7cPV3aqYOF9p0bIw6rdHP94-K04IaeRgSHQBfBbQbEZfEteRVcj_DuuR6R7-dnN5tvxeX114vNyWXhpVSyaEvpSy8kqBp0CN6D0U5oxT1vmfAGoFGs1WXlGu1b4EHwJkijmtI0FS-dPCJfnrz7uRmg9TBO2fV2n-Pg8r1NLtp_J2Ps7G36ZY1kWpRmEXx8FuT0cwac7BDRQ9-7EdKMdmGU4pVmK_rhP3SX5rx89JFilRS6Egv16YnyOSFmCH-O4cyumdo1U_uYqfwNAPiVGQ</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Xue, Mingshan</creator><creator>Zhang, Teng</creator><creator>Cheng, Zhangkai J.</creator><creator>Guo, Baojun</creator><creator>Zeng, Yifeng</creator><creator>Lin, Runpei</creator><creator>Zheng, Peiyan</creator><creator>Liu, Mingtao</creator><creator>Hu, Fengyu</creator><creator>Li, Feng</creator><creator>Zhang, Wensheng</creator><creator>Li, Lu</creator><creator>Zhao, Qi</creator><creator>Sun, Baoqing</creator><creator>Tang, Xiaoping</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220101</creationdate><title>Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression</title><author>Xue, Mingshan ; Zhang, Teng ; Cheng, Zhangkai J. ; Guo, Baojun ; Zeng, Yifeng ; Lin, Runpei ; Zheng, Peiyan ; Liu, Mingtao ; Hu, Fengyu ; Li, Feng ; Zhang, Wensheng ; Li, Lu ; Zhao, Qi ; Sun, Baoqing ; Tang, Xiaoping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3343-d63c6c23e48e5ffcce95a2541c1d02c9eeb40d567ab5cde1f21bf394b69b716a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acids</topic><topic>Blood diseases</topic><topic>Ceramide</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Discriminant analysis</topic><topic>Fibrin</topic><topic>Inflammation</topic><topic>Kidneys</topic><topic>Lecithin</topic><topic>Lipopolysaccharides</topic><topic>Mass spectrometry</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Patients</topic><topic>Phosphatidylcholine</topic><topic>Phosphatidylinositol</topic><topic>Phospholipids</topic><topic>Plasma</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Research Paper</topic><topic>Scientific imaging</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Signal transduction</topic><topic>Variables</topic><topic>Vortices</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xue, Mingshan</creatorcontrib><creatorcontrib>Zhang, Teng</creatorcontrib><creatorcontrib>Cheng, Zhangkai J.</creatorcontrib><creatorcontrib>Guo, Baojun</creatorcontrib><creatorcontrib>Zeng, Yifeng</creatorcontrib><creatorcontrib>Lin, Runpei</creatorcontrib><creatorcontrib>Zheng, Peiyan</creatorcontrib><creatorcontrib>Liu, Mingtao</creatorcontrib><creatorcontrib>Hu, Fengyu</creatorcontrib><creatorcontrib>Li, Feng</creatorcontrib><creatorcontrib>Zhang, Wensheng</creatorcontrib><creatorcontrib>Li, Lu</creatorcontrib><creatorcontrib>Zhao, Qi</creatorcontrib><creatorcontrib>Sun, Baoqing</creatorcontrib><creatorcontrib>Tang, Xiaoping</creatorcontrib><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of biological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xue, Mingshan</au><au>Zhang, Teng</au><au>Cheng, Zhangkai J.</au><au>Guo, Baojun</au><au>Zeng, Yifeng</au><au>Lin, Runpei</au><au>Zheng, Peiyan</au><au>Liu, Mingtao</au><au>Hu, Fengyu</au><au>Li, Feng</au><au>Zhang, Wensheng</au><au>Li, Lu</au><au>Zhao, Qi</au><au>Sun, Baoqing</au><au>Tang, Xiaoping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression</atitle><jtitle>International journal of biological sciences</jtitle><date>2022-01-01</date><risdate>2022</risdate><volume>18</volume><issue>12</issue><spage>4618</spage><epage>4628</epage><pages>4618-4628</pages><issn>1449-2288</issn><eissn>1449-2288</eissn><abstract>This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P&lt; 0.05) between patients and healthy controls (P&lt; 0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.</abstract><cop>Sydney</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>35874944</pmid><doi>10.7150/ijbs.72450</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1449-2288
ispartof International journal of biological sciences, 2022-01, Vol.18 (12), p.4618-4628
issn 1449-2288
1449-2288
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9305269
source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central
subjects Acids
Blood diseases
Ceramide
Coronaviruses
COVID-19
Discriminant analysis
Fibrin
Inflammation
Kidneys
Lecithin
Lipopolysaccharides
Mass spectrometry
Metabolic pathways
Metabolism
Metabolites
Metabolomics
Patients
Phosphatidylcholine
Phosphatidylinositol
Phospholipids
Plasma
Proteins
Proteomics
Research Paper
Scientific imaging
Severe acute respiratory syndrome coronavirus 2
Signal transduction
Variables
Vortices
title Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T12%3A56%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20a%20Functional%20Phospholipid%20Metabolome-Protein%20Association%20Pathway%20on%20the%20Mechanism%20of%20COVID-19%20Disease%20Progression&rft.jtitle=International%20journal%20of%20biological%20sciences&rft.au=Xue,%20Mingshan&rft.date=2022-01-01&rft.volume=18&rft.issue=12&rft.spage=4618&rft.epage=4628&rft.pages=4618-4628&rft.issn=1449-2288&rft.eissn=1449-2288&rft_id=info:doi/10.7150/ijbs.72450&rft_dat=%3Cproquest_pubme%3E2694417509%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2690732572&rft_id=info:pmid/35874944&rfr_iscdi=true