Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows
In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material,...
Gespeichert in:
Veröffentlicht in: | Functional & integrative genomics 2022-02, Vol.22 (1), p.77-87 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 87 |
---|---|
container_issue | 1 |
container_start_page | 77 |
container_title | Functional & integrative genomics |
container_volume | 22 |
creator | Wang, Yue Fang, Jian Zeng, Han-Fang Zhong, Ji-Feng Li, Hui-Xia Chen, Kun-Lin |
description | In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins, and lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNA profile of heat-stressed and normal Holstein cows. We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was upregulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action. In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows. |
doi_str_mv | 10.1007/s10142-021-00814-8 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2604457667</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2621099826</sourcerecordid><originalsourceid>FETCH-LOGICAL-c419t-e93696625312be0f7cc92c25edffaebeadb575b2aaae28de279072c67c28dee33</originalsourceid><addsrcrecordid>eNp9kc9u1DAQxiNERUvhBTigSFy4hI7_JI6PVVXaShVIVZG4WY4zBhcnXjxZwb5EnxlvdymIAyd7Zn7fN7K_qnrF4B0DUCfEgEneAGcNQM9k0z-pjpgUfaO07J8-3sXnw-o50R0AtKDFs-pQyF5oCXBU3V-NOC_BB2eXkObazmM9hBRmn_JUWo5Ky8YNBaqTr8fgPeatwsa4qfHnKiMRjvUU4rdSJkqTjaVyOd18OKU6zH-P8MHkK9qloWWvvEyRFiycSz_oRXXgbSR8uT-Pq0_vz2_PLpvrjxdXZ6fXjZNMLw1q0emu461gfEDwyjnNHW9x9N7igHYcWtUO3FqLvB-RKw2Ku065bYVCHFdvd76rnL6vkRYzBXIYo50xrcnwDqRsVdepgr75B71L61z-ZEtxBlr3vCsU31Hl4UQZvVnlMNm8MQzMNi2zS8uUtMxDWqYvotd76_Uw4fgo-R1PAcQOoDKav2D-s_s_tr8AVn6jxg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2621099826</pqid></control><display><type>article</type><title>Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Wang, Yue ; Fang, Jian ; Zeng, Han-Fang ; Zhong, Ji-Feng ; Li, Hui-Xia ; Chen, Kun-Lin</creator><creatorcontrib>Wang, Yue ; Fang, Jian ; Zeng, Han-Fang ; Zhong, Ji-Feng ; Li, Hui-Xia ; Chen, Kun-Lin</creatorcontrib><description>In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins, and lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNA profile of heat-stressed and normal Holstein cows. We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was upregulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action. In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows.</description><identifier>ISSN: 1438-793X</identifier><identifier>EISSN: 1438-7948</identifier><identifier>DOI: 10.1007/s10142-021-00814-8</identifier><identifier>PMID: 34839400</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animal Genetics and Genomics ; Animals ; Apoptosis ; Autophagy ; Biochemistry ; Bioinformatics ; Biomedical and Life Sciences ; Cattle ; Cell Biology ; Computational Biology ; Cow's milk ; Dairy cattle ; Exosomes ; Exosomes - genetics ; Female ; Gene Expression Profiling ; Heat stress ; Heat-Shock Response - genetics ; Hyperthermia ; Life Sciences ; Lipids ; Mammary gland ; MAP kinase ; Microbial Genetics and Genomics ; MicroRNAs ; MicroRNAs - genetics ; Milk ; Milk - chemistry ; miRNA ; Original Article ; Plant Genetics and Genomics</subject><ispartof>Functional & integrative genomics, 2022-02, Vol.22 (1), p.77-87</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-e93696625312be0f7cc92c25edffaebeadb575b2aaae28de279072c67c28dee33</citedby><cites>FETCH-LOGICAL-c419t-e93696625312be0f7cc92c25edffaebeadb575b2aaae28de279072c67c28dee33</cites><orcidid>0000-0002-8398-6922</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10142-021-00814-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10142-021-00814-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34839400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Fang, Jian</creatorcontrib><creatorcontrib>Zeng, Han-Fang</creatorcontrib><creatorcontrib>Zhong, Ji-Feng</creatorcontrib><creatorcontrib>Li, Hui-Xia</creatorcontrib><creatorcontrib>Chen, Kun-Lin</creatorcontrib><title>Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows</title><title>Functional & integrative genomics</title><addtitle>Funct Integr Genomics</addtitle><addtitle>Funct Integr Genomics</addtitle><description>In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins, and lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNA profile of heat-stressed and normal Holstein cows. We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was upregulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action. In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows.</description><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Cattle</subject><subject>Cell Biology</subject><subject>Computational Biology</subject><subject>Cow's milk</subject><subject>Dairy cattle</subject><subject>Exosomes</subject><subject>Exosomes - genetics</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Heat stress</subject><subject>Heat-Shock Response - genetics</subject><subject>Hyperthermia</subject><subject>Life Sciences</subject><subject>Lipids</subject><subject>Mammary gland</subject><subject>MAP kinase</subject><subject>Microbial Genetics and Genomics</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Milk</subject><subject>Milk - chemistry</subject><subject>miRNA</subject><subject>Original Article</subject><subject>Plant Genetics and Genomics</subject><issn>1438-793X</issn><issn>1438-7948</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc9u1DAQxiNERUvhBTigSFy4hI7_JI6PVVXaShVIVZG4WY4zBhcnXjxZwb5EnxlvdymIAyd7Zn7fN7K_qnrF4B0DUCfEgEneAGcNQM9k0z-pjpgUfaO07J8-3sXnw-o50R0AtKDFs-pQyF5oCXBU3V-NOC_BB2eXkObazmM9hBRmn_JUWo5Ky8YNBaqTr8fgPeatwsa4qfHnKiMRjvUU4rdSJkqTjaVyOd18OKU6zH-P8MHkK9qloWWvvEyRFiycSz_oRXXgbSR8uT-Pq0_vz2_PLpvrjxdXZ6fXjZNMLw1q0emu461gfEDwyjnNHW9x9N7igHYcWtUO3FqLvB-RKw2Ku065bYVCHFdvd76rnL6vkRYzBXIYo50xrcnwDqRsVdepgr75B71L61z-ZEtxBlr3vCsU31Hl4UQZvVnlMNm8MQzMNi2zS8uUtMxDWqYvotd76_Uw4fgo-R1PAcQOoDKav2D-s_s_tr8AVn6jxg</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Wang, Yue</creator><creator>Fang, Jian</creator><creator>Zeng, Han-Fang</creator><creator>Zhong, Ji-Feng</creator><creator>Li, Hui-Xia</creator><creator>Chen, Kun-Lin</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PADUT</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8398-6922</orcidid></search><sort><creationdate>20220201</creationdate><title>Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows</title><author>Wang, Yue ; Fang, Jian ; Zeng, Han-Fang ; Zhong, Ji-Feng ; Li, Hui-Xia ; Chen, Kun-Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-e93696625312be0f7cc92c25edffaebeadb575b2aaae28de279072c67c28dee33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Cattle</topic><topic>Cell Biology</topic><topic>Computational Biology</topic><topic>Cow's milk</topic><topic>Dairy cattle</topic><topic>Exosomes</topic><topic>Exosomes - genetics</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Heat stress</topic><topic>Heat-Shock Response - genetics</topic><topic>Hyperthermia</topic><topic>Life Sciences</topic><topic>Lipids</topic><topic>Mammary gland</topic><topic>MAP kinase</topic><topic>Microbial Genetics and Genomics</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>Milk</topic><topic>Milk - chemistry</topic><topic>miRNA</topic><topic>Original Article</topic><topic>Plant Genetics and Genomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Fang, Jian</creatorcontrib><creatorcontrib>Zeng, Han-Fang</creatorcontrib><creatorcontrib>Zhong, Ji-Feng</creatorcontrib><creatorcontrib>Li, Hui-Xia</creatorcontrib><creatorcontrib>Chen, Kun-Lin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Research Library China</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Functional & integrative genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yue</au><au>Fang, Jian</au><au>Zeng, Han-Fang</au><au>Zhong, Ji-Feng</au><au>Li, Hui-Xia</au><au>Chen, Kun-Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows</atitle><jtitle>Functional & integrative genomics</jtitle><stitle>Funct Integr Genomics</stitle><addtitle>Funct Integr Genomics</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>22</volume><issue>1</issue><spage>77</spage><epage>87</epage><pages>77-87</pages><issn>1438-793X</issn><eissn>1438-7948</eissn><abstract>In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins, and lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNA profile of heat-stressed and normal Holstein cows. We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was upregulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action. In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34839400</pmid><doi>10.1007/s10142-021-00814-8</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8398-6922</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1438-793X |
ispartof | Functional & integrative genomics, 2022-02, Vol.22 (1), p.77-87 |
issn | 1438-793X 1438-7948 |
language | eng |
recordid | cdi_proquest_miscellaneous_2604457667 |
source | MEDLINE; Springer Nature - Complete Springer Journals |
subjects | Animal Genetics and Genomics Animals Apoptosis Autophagy Biochemistry Bioinformatics Biomedical and Life Sciences Cattle Cell Biology Computational Biology Cow's milk Dairy cattle Exosomes Exosomes - genetics Female Gene Expression Profiling Heat stress Heat-Shock Response - genetics Hyperthermia Life Sciences Lipids Mammary gland MAP kinase Microbial Genetics and Genomics MicroRNAs MicroRNAs - genetics Milk Milk - chemistry miRNA Original Article Plant Genetics and Genomics |
title | Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat-stressed Holstein cows |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T12%3A05%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20and%20bioinformatics%20analysis%20of%20differentially%20expressed%20milk%20exosomal%20microRNAs%20in%20milk%20exosomes%20of%20heat-stressed%20Holstein%20cows&rft.jtitle=Functional%20&%20integrative%20genomics&rft.au=Wang,%20Yue&rft.date=2022-02-01&rft.volume=22&rft.issue=1&rft.spage=77&rft.epage=87&rft.pages=77-87&rft.issn=1438-793X&rft.eissn=1438-7948&rft_id=info:doi/10.1007/s10142-021-00814-8&rft_dat=%3Cproquest_cross%3E2621099826%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2621099826&rft_id=info:pmid/34839400&rfr_iscdi=true |