Loading…

A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis

D-lactate dehydrogenase (D-LDH) converts D-lactate (the end product of glyoxalase system) to pyruvate and thereby completes the detoxification process of methylglyoxal. D-LDH detoxifies and diverts the stress induced toxic metabolites, MG and D-lactate, towards energy production and thus, protects t...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2020-07, Vol.10 (1), p.12835, Article 12835
Main Authors: Jain, Muskan, Aggarwal, Sakshi, Nagar, Preeti, Tiwari, Roopam, Mustafiz, Ananda
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3
cites cdi_FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3
container_end_page
container_issue 1
container_start_page 12835
container_title Scientific reports
container_volume 10
creator Jain, Muskan
Aggarwal, Sakshi
Nagar, Preeti
Tiwari, Roopam
Mustafiz, Ananda
description D-lactate dehydrogenase (D-LDH) converts D-lactate (the end product of glyoxalase system) to pyruvate and thereby completes the detoxification process of methylglyoxal. D-LDH detoxifies and diverts the stress induced toxic metabolites, MG and D-lactate, towards energy production and thus, protects the cell from their deteriorating effects. In this study, a D-LDH enzyme from rice (OsD-LDH2, encoded by Os07g08950.1) was characterized for its role in abiotic stress tolerance. For this, a combination of in silico, molecular, genetic and biochemical approaches was used. The kinetic analysis revealed OsD-LDH2 to be the most efficient D-LDH enzyme in comparison to D-LDHs from other plant species. Heterologous overexpression of OsD-LDH2 provides tolerance against multiple abiotic stresses in E. coli , yeast and plant system. The analysis of D-LDH mutant and OsD-LDH2 overexpressing transgenic plants uncovered the crucial role of D-LDH in mitigation of abiotic stresses. OsD-LDH2 overexpressing plants maintained lower level of ROS and other toxic metabolites along with better functioning of antioxidant system. This is the first report on correlation of D-LDH with multiple abiotic stress tolerance. Overall, OsD-LDH2 emerged as a promising candidate which can open a new direction for engineering stress tolerant crop varieties by maintaining their growth and yield in unfavorable conditions.
doi_str_mv 10.1038/s41598-020-69742-0
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7393112</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2428758696</sourcerecordid><originalsourceid>FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3</originalsourceid><addsrcrecordid>eNp9UctqHDEQHEJCbBz_QA5BkPMkeoxel4BxHg4YcknOQtL07MpoRhtJs7B_kM-ONms7ziUNogtUVd10dd1rgt8RzNT7MhCuVY8p7oWWA-3xs-6c4oH3lFH6_Ak-6y5LucOtONUD0S-7M0Yla3g4735doY99tL7aCmiE7WHMaQOLLYCmnGaUgwcUCgrLPsU9jA0gn5YJcg7LBtUUIdulcWpC8xpr2EVA1oVUg0elZigFCnIHNNuw1PaOKg8xrtFmtE0zpFJtCeVV92KyscDlfb_ofnz-9P36pr_99uXr9dVt77nAtVfOUS0pY4Jrq5zi06Slw6OQMHKvwWMp-QROCAJEEc65A6K5FspZMVLPLroPJ9_d6mYYPSw122h2Ocw2H0yywfz7s4St2aS9kUwzQmgzeHtvkNPPFUo1d2nNS9vZ0IEqyZXQorHoieVzKiXD9DiBYHMM0JwCNC1A8ydAg5vozdPdHiUPcTUCOxHK7nh-yH9n_8f2N0qDqjM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2428758696</pqid></control><display><type>article</type><title>A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Jain, Muskan ; Aggarwal, Sakshi ; Nagar, Preeti ; Tiwari, Roopam ; Mustafiz, Ananda</creator><creatorcontrib>Jain, Muskan ; Aggarwal, Sakshi ; Nagar, Preeti ; Tiwari, Roopam ; Mustafiz, Ananda</creatorcontrib><description>D-lactate dehydrogenase (D-LDH) converts D-lactate (the end product of glyoxalase system) to pyruvate and thereby completes the detoxification process of methylglyoxal. D-LDH detoxifies and diverts the stress induced toxic metabolites, MG and D-lactate, towards energy production and thus, protects the cell from their deteriorating effects. In this study, a D-LDH enzyme from rice (OsD-LDH2, encoded by Os07g08950.1) was characterized for its role in abiotic stress tolerance. For this, a combination of in silico, molecular, genetic and biochemical approaches was used. The kinetic analysis revealed OsD-LDH2 to be the most efficient D-LDH enzyme in comparison to D-LDHs from other plant species. Heterologous overexpression of OsD-LDH2 provides tolerance against multiple abiotic stresses in E. coli , yeast and plant system. The analysis of D-LDH mutant and OsD-LDH2 overexpressing transgenic plants uncovered the crucial role of D-LDH in mitigation of abiotic stresses. OsD-LDH2 overexpressing plants maintained lower level of ROS and other toxic metabolites along with better functioning of antioxidant system. This is the first report on correlation of D-LDH with multiple abiotic stress tolerance. Overall, OsD-LDH2 emerged as a promising candidate which can open a new direction for engineering stress tolerant crop varieties by maintaining their growth and yield in unfavorable conditions.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-69742-0</identifier><identifier>PMID: 32732944</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/337 ; 631/449 ; Abiotic stress ; Antioxidants ; Computer Simulation ; D-Lactate dehydrogenase ; Dehydrogenase ; Dehydrogenases ; Detoxification ; E coli ; Enzymes ; Gene Expression ; Homeostasis ; Homeostasis - physiology ; Humanities and Social Sciences ; L-Lactate dehydrogenase ; Lactate Dehydrogenases - genetics ; Lactate Dehydrogenases - metabolism ; Lactate Dehydrogenases - physiology ; Lactic acid ; Metabolites ; multidisciplinary ; Oryza - enzymology ; Oryza - genetics ; Oryza - metabolism ; Oryza - physiology ; Plant species ; Pyruvaldehyde ; Pyruvaldehyde - metabolism ; Pyruvic acid ; Reactive Oxygen Species - metabolism ; Rice ; Science ; Science (multidisciplinary) ; Stress, Physiological - genetics ; Transgenic plants ; Yeasts</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.12835, Article 12835</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3</citedby><cites>FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2428758696/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2428758696?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32732944$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jain, Muskan</creatorcontrib><creatorcontrib>Aggarwal, Sakshi</creatorcontrib><creatorcontrib>Nagar, Preeti</creatorcontrib><creatorcontrib>Tiwari, Roopam</creatorcontrib><creatorcontrib>Mustafiz, Ananda</creatorcontrib><title>A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>D-lactate dehydrogenase (D-LDH) converts D-lactate (the end product of glyoxalase system) to pyruvate and thereby completes the detoxification process of methylglyoxal. D-LDH detoxifies and diverts the stress induced toxic metabolites, MG and D-lactate, towards energy production and thus, protects the cell from their deteriorating effects. In this study, a D-LDH enzyme from rice (OsD-LDH2, encoded by Os07g08950.1) was characterized for its role in abiotic stress tolerance. For this, a combination of in silico, molecular, genetic and biochemical approaches was used. The kinetic analysis revealed OsD-LDH2 to be the most efficient D-LDH enzyme in comparison to D-LDHs from other plant species. Heterologous overexpression of OsD-LDH2 provides tolerance against multiple abiotic stresses in E. coli , yeast and plant system. The analysis of D-LDH mutant and OsD-LDH2 overexpressing transgenic plants uncovered the crucial role of D-LDH in mitigation of abiotic stresses. OsD-LDH2 overexpressing plants maintained lower level of ROS and other toxic metabolites along with better functioning of antioxidant system. This is the first report on correlation of D-LDH with multiple abiotic stress tolerance. Overall, OsD-LDH2 emerged as a promising candidate which can open a new direction for engineering stress tolerant crop varieties by maintaining their growth and yield in unfavorable conditions.</description><subject>631/337</subject><subject>631/449</subject><subject>Abiotic stress</subject><subject>Antioxidants</subject><subject>Computer Simulation</subject><subject>D-Lactate dehydrogenase</subject><subject>Dehydrogenase</subject><subject>Dehydrogenases</subject><subject>Detoxification</subject><subject>E coli</subject><subject>Enzymes</subject><subject>Gene Expression</subject><subject>Homeostasis</subject><subject>Homeostasis - physiology</subject><subject>Humanities and Social Sciences</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate Dehydrogenases - genetics</subject><subject>Lactate Dehydrogenases - metabolism</subject><subject>Lactate Dehydrogenases - physiology</subject><subject>Lactic acid</subject><subject>Metabolites</subject><subject>multidisciplinary</subject><subject>Oryza - enzymology</subject><subject>Oryza - genetics</subject><subject>Oryza - metabolism</subject><subject>Oryza - physiology</subject><subject>Plant species</subject><subject>Pyruvaldehyde</subject><subject>Pyruvaldehyde - metabolism</subject><subject>Pyruvic acid</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Rice</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stress, Physiological - genetics</subject><subject>Transgenic plants</subject><subject>Yeasts</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp9UctqHDEQHEJCbBz_QA5BkPMkeoxel4BxHg4YcknOQtL07MpoRhtJs7B_kM-ONms7ziUNogtUVd10dd1rgt8RzNT7MhCuVY8p7oWWA-3xs-6c4oH3lFH6_Ak-6y5LucOtONUD0S-7M0Yla3g4735doY99tL7aCmiE7WHMaQOLLYCmnGaUgwcUCgrLPsU9jA0gn5YJcg7LBtUUIdulcWpC8xpr2EVA1oVUg0elZigFCnIHNNuw1PaOKg8xrtFmtE0zpFJtCeVV92KyscDlfb_ofnz-9P36pr_99uXr9dVt77nAtVfOUS0pY4Jrq5zi06Slw6OQMHKvwWMp-QROCAJEEc65A6K5FspZMVLPLroPJ9_d6mYYPSw122h2Ocw2H0yywfz7s4St2aS9kUwzQmgzeHtvkNPPFUo1d2nNS9vZ0IEqyZXQorHoieVzKiXD9DiBYHMM0JwCNC1A8ydAg5vozdPdHiUPcTUCOxHK7nh-yH9n_8f2N0qDqjM</recordid><startdate>20200730</startdate><enddate>20200730</enddate><creator>Jain, Muskan</creator><creator>Aggarwal, Sakshi</creator><creator>Nagar, Preeti</creator><creator>Tiwari, Roopam</creator><creator>Mustafiz, Ananda</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20200730</creationdate><title>A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis</title><author>Jain, Muskan ; Aggarwal, Sakshi ; Nagar, Preeti ; Tiwari, Roopam ; Mustafiz, Ananda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/337</topic><topic>631/449</topic><topic>Abiotic stress</topic><topic>Antioxidants</topic><topic>Computer Simulation</topic><topic>D-Lactate dehydrogenase</topic><topic>Dehydrogenase</topic><topic>Dehydrogenases</topic><topic>Detoxification</topic><topic>E coli</topic><topic>Enzymes</topic><topic>Gene Expression</topic><topic>Homeostasis</topic><topic>Homeostasis - physiology</topic><topic>Humanities and Social Sciences</topic><topic>L-Lactate dehydrogenase</topic><topic>Lactate Dehydrogenases - genetics</topic><topic>Lactate Dehydrogenases - metabolism</topic><topic>Lactate Dehydrogenases - physiology</topic><topic>Lactic acid</topic><topic>Metabolites</topic><topic>multidisciplinary</topic><topic>Oryza - enzymology</topic><topic>Oryza - genetics</topic><topic>Oryza - metabolism</topic><topic>Oryza - physiology</topic><topic>Plant species</topic><topic>Pyruvaldehyde</topic><topic>Pyruvaldehyde - metabolism</topic><topic>Pyruvic acid</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Rice</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stress, Physiological - genetics</topic><topic>Transgenic plants</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jain, Muskan</creatorcontrib><creatorcontrib>Aggarwal, Sakshi</creatorcontrib><creatorcontrib>Nagar, Preeti</creatorcontrib><creatorcontrib>Tiwari, Roopam</creatorcontrib><creatorcontrib>Mustafiz, Ananda</creatorcontrib><collection>SpringerOpen</collection><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>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest Biological Science Journals</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 Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jain, Muskan</au><au>Aggarwal, Sakshi</au><au>Nagar, Preeti</au><au>Tiwari, Roopam</au><au>Mustafiz, Ananda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-30</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>12835</spage><pages>12835-</pages><artnum>12835</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>D-lactate dehydrogenase (D-LDH) converts D-lactate (the end product of glyoxalase system) to pyruvate and thereby completes the detoxification process of methylglyoxal. D-LDH detoxifies and diverts the stress induced toxic metabolites, MG and D-lactate, towards energy production and thus, protects the cell from their deteriorating effects. In this study, a D-LDH enzyme from rice (OsD-LDH2, encoded by Os07g08950.1) was characterized for its role in abiotic stress tolerance. For this, a combination of in silico, molecular, genetic and biochemical approaches was used. The kinetic analysis revealed OsD-LDH2 to be the most efficient D-LDH enzyme in comparison to D-LDHs from other plant species. Heterologous overexpression of OsD-LDH2 provides tolerance against multiple abiotic stresses in E. coli , yeast and plant system. The analysis of D-LDH mutant and OsD-LDH2 overexpressing transgenic plants uncovered the crucial role of D-LDH in mitigation of abiotic stresses. OsD-LDH2 overexpressing plants maintained lower level of ROS and other toxic metabolites along with better functioning of antioxidant system. This is the first report on correlation of D-LDH with multiple abiotic stress tolerance. Overall, OsD-LDH2 emerged as a promising candidate which can open a new direction for engineering stress tolerant crop varieties by maintaining their growth and yield in unfavorable conditions.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32732944</pmid><doi>10.1038/s41598-020-69742-0</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2045-2322
ispartof Scientific reports, 2020-07, Vol.10 (1), p.12835, Article 12835
issn 2045-2322
2045-2322
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7393112
source Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access
subjects 631/337
631/449
Abiotic stress
Antioxidants
Computer Simulation
D-Lactate dehydrogenase
Dehydrogenase
Dehydrogenases
Detoxification
E coli
Enzymes
Gene Expression
Homeostasis
Homeostasis - physiology
Humanities and Social Sciences
L-Lactate dehydrogenase
Lactate Dehydrogenases - genetics
Lactate Dehydrogenases - metabolism
Lactate Dehydrogenases - physiology
Lactic acid
Metabolites
multidisciplinary
Oryza - enzymology
Oryza - genetics
Oryza - metabolism
Oryza - physiology
Plant species
Pyruvaldehyde
Pyruvaldehyde - metabolism
Pyruvic acid
Reactive Oxygen Species - metabolism
Rice
Science
Science (multidisciplinary)
Stress, Physiological - genetics
Transgenic plants
Yeasts
title A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T22%3A11%3A34IST&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=A%20D-lactate%20dehydrogenase%20from%20rice%20is%20involved%20in%20conferring%20tolerance%20to%20multiple%20abiotic%20stresses%20by%20maintaining%20cellular%20homeostasis&rft.jtitle=Scientific%20reports&rft.au=Jain,%20Muskan&rft.date=2020-07-30&rft.volume=10&rft.issue=1&rft.spage=12835&rft.pages=12835-&rft.artnum=12835&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-69742-0&rft_dat=%3Cproquest_pubme%3E2428758696%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c560t-8bb297233659a8b85ff97b0d67ed5c9ec0775feb661e181555be195968ba6d2c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2428758696&rft_id=info:pmid/32732944&rfr_iscdi=true