Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms
OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP...
Gespeichert in:
Veröffentlicht in: | The Science of the total environment 2022-08, Vol.832, p.155006-155006, Article 155006 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 155006 |
---|---|
container_issue | |
container_start_page | 155006 |
container_title | The Science of the total environment |
container_volume | 832 |
creator | Tang, Li Dong, Jiayu Qu, Mengmeng Lv, Qiming Zhang, Liping Peng, Can Hu, Yuanyi Li, Yaokui Ji, Zhongying Mao, Bigang Peng, Yan Shao, Ye Zhao, Bingran |
description | OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.
[Display omitted]
•Knockout of OsNRAMP5 confers cadmium (Cd) tolerance of rice in a wide range of external Cd concentrations.•Knockout of OsNRAMP5 decreases Cd uptake but simultaneously facilitates Cd translocation from roots to shoots.•The impact of OsNRAMP5 knockout on Cd accumulation in above-ground tissues depends on external Cd concentrations.•Knockout of OsNRAMP5 complements deficient minerals in shoots, indirectly enhancing rice tolerance to severe Cd stress. |
doi_str_mv | 10.1016/j.scitotenv.2022.155006 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2660998927</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S004896972202099X</els_id><sourcerecordid>2647654326</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-a11904aec9c8e52a14ce0ff3c791eb469cb3f2525728f848d9947f6a4f71fce83</originalsourceid><addsrcrecordid>eNqNUctuEzEUtRCIpoVfAC_ZTLA9Hj-WUUUBtVCEYG05nmtwyNjB9kTtV_DLOKRkC974Xvk8rHMQeknJkhIqXm-WxYWaKsT9khHGlnQYCBGP0IIqqTtKmHiMFoRw1Wmh5Rk6L2VD2pGKPkVn_dAryrhYoF_XMbkfaa44eXxbPn5effg0YIjfbXRQcA4OcE1byIe9TdjZcQrz1Ma70L5wj0PEGcouxfLnfW_zfYjfMNxVyNFuTwSXmkKs2dbQsHgfLB5DqSG6iidwzTCUqTxDT7zdFnj-cF-gr1dvvly-625u376_XN10jg997SylmnALTjsFA7OUOyDe905qCmsutFv3ng1skEx5xdWoNZdeWO4l9Q5Uf4FeHXV3Of2coVQzheJgu7UR0lwME4JorTST_wHlUgy8Z6JB5RHqciolgze7HKaWiKHEHIozG3MqzhyKM8fiGvPFg8m8nmA88f421QCrIwBaKvsA-SAELdIxZHDVjCn80-Q3dwuxTg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2647654326</pqid></control><display><type>article</type><title>Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Tang, Li ; Dong, Jiayu ; Qu, Mengmeng ; Lv, Qiming ; Zhang, Liping ; Peng, Can ; Hu, Yuanyi ; Li, Yaokui ; Ji, Zhongying ; Mao, Bigang ; Peng, Yan ; Shao, Ye ; Zhao, Bingran</creator><creatorcontrib>Tang, Li ; Dong, Jiayu ; Qu, Mengmeng ; Lv, Qiming ; Zhang, Liping ; Peng, Can ; Hu, Yuanyi ; Li, Yaokui ; Ji, Zhongying ; Mao, Bigang ; Peng, Yan ; Shao, Ye ; Zhao, Bingran</creatorcontrib><description>OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.
[Display omitted]
•Knockout of OsNRAMP5 confers cadmium (Cd) tolerance of rice in a wide range of external Cd concentrations.•Knockout of OsNRAMP5 decreases Cd uptake but simultaneously facilitates Cd translocation from roots to shoots.•The impact of OsNRAMP5 knockout on Cd accumulation in above-ground tissues depends on external Cd concentrations.•Knockout of OsNRAMP5 complements deficient minerals in shoots, indirectly enhancing rice tolerance to severe Cd stress.</description><identifier>ISSN: 0048-9697</identifier><identifier>EISSN: 1879-1026</identifier><identifier>DOI: 10.1016/j.scitotenv.2022.155006</identifier><identifier>PMID: 35381246</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Biological Transport ; cadmium ; Cadmium - metabolism ; Cadmium toxicity ; environment ; Manganese ; Manganese - metabolism ; Membrane Transport Proteins - genetics ; Membrane Transport Proteins - metabolism ; Membrane Transport Proteins - pharmacology ; Metal transporter ; mutation ; Oryza - metabolism ; OsNRAMP5 ; Plant Roots - metabolism ; rice ; Rice (Oryza sativa L.) ; risk ; toxicity</subject><ispartof>The Science of the total environment, 2022-08, Vol.832, p.155006-155006, Article 155006</ispartof><rights>2022 The Authors</rights><rights>Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-a11904aec9c8e52a14ce0ff3c791eb469cb3f2525728f848d9947f6a4f71fce83</citedby><cites>FETCH-LOGICAL-c453t-a11904aec9c8e52a14ce0ff3c791eb469cb3f2525728f848d9947f6a4f71fce83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S004896972202099X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35381246$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Li</creatorcontrib><creatorcontrib>Dong, Jiayu</creatorcontrib><creatorcontrib>Qu, Mengmeng</creatorcontrib><creatorcontrib>Lv, Qiming</creatorcontrib><creatorcontrib>Zhang, Liping</creatorcontrib><creatorcontrib>Peng, Can</creatorcontrib><creatorcontrib>Hu, Yuanyi</creatorcontrib><creatorcontrib>Li, Yaokui</creatorcontrib><creatorcontrib>Ji, Zhongying</creatorcontrib><creatorcontrib>Mao, Bigang</creatorcontrib><creatorcontrib>Peng, Yan</creatorcontrib><creatorcontrib>Shao, Ye</creatorcontrib><creatorcontrib>Zhao, Bingran</creatorcontrib><title>Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms</title><title>The Science of the total environment</title><addtitle>Sci Total Environ</addtitle><description>OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.
[Display omitted]
•Knockout of OsNRAMP5 confers cadmium (Cd) tolerance of rice in a wide range of external Cd concentrations.•Knockout of OsNRAMP5 decreases Cd uptake but simultaneously facilitates Cd translocation from roots to shoots.•The impact of OsNRAMP5 knockout on Cd accumulation in above-ground tissues depends on external Cd concentrations.•Knockout of OsNRAMP5 complements deficient minerals in shoots, indirectly enhancing rice tolerance to severe Cd stress.</description><subject>Biological Transport</subject><subject>cadmium</subject><subject>Cadmium - metabolism</subject><subject>Cadmium toxicity</subject><subject>environment</subject><subject>Manganese</subject><subject>Manganese - metabolism</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Membrane Transport Proteins - pharmacology</subject><subject>Metal transporter</subject><subject>mutation</subject><subject>Oryza - metabolism</subject><subject>OsNRAMP5</subject><subject>Plant Roots - metabolism</subject><subject>rice</subject><subject>Rice (Oryza sativa L.)</subject><subject>risk</subject><subject>toxicity</subject><issn>0048-9697</issn><issn>1879-1026</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUctuEzEUtRCIpoVfAC_ZTLA9Hj-WUUUBtVCEYG05nmtwyNjB9kTtV_DLOKRkC974Xvk8rHMQeknJkhIqXm-WxYWaKsT9khHGlnQYCBGP0IIqqTtKmHiMFoRw1Wmh5Rk6L2VD2pGKPkVn_dAryrhYoF_XMbkfaa44eXxbPn5effg0YIjfbXRQcA4OcE1byIe9TdjZcQrz1Ma70L5wj0PEGcouxfLnfW_zfYjfMNxVyNFuTwSXmkKs2dbQsHgfLB5DqSG6iidwzTCUqTxDT7zdFnj-cF-gr1dvvly-625u376_XN10jg997SylmnALTjsFA7OUOyDe905qCmsutFv3ng1skEx5xdWoNZdeWO4l9Q5Uf4FeHXV3Of2coVQzheJgu7UR0lwME4JorTST_wHlUgy8Z6JB5RHqciolgze7HKaWiKHEHIozG3MqzhyKM8fiGvPFg8m8nmA88f421QCrIwBaKvsA-SAELdIxZHDVjCn80-Q3dwuxTg</recordid><startdate>20220801</startdate><enddate>20220801</enddate><creator>Tang, Li</creator><creator>Dong, Jiayu</creator><creator>Qu, Mengmeng</creator><creator>Lv, Qiming</creator><creator>Zhang, Liping</creator><creator>Peng, Can</creator><creator>Hu, Yuanyi</creator><creator>Li, Yaokui</creator><creator>Ji, Zhongying</creator><creator>Mao, Bigang</creator><creator>Peng, Yan</creator><creator>Shao, Ye</creator><creator>Zhao, Bingran</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20220801</creationdate><title>Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms</title><author>Tang, Li ; Dong, Jiayu ; Qu, Mengmeng ; Lv, Qiming ; Zhang, Liping ; Peng, Can ; Hu, Yuanyi ; Li, Yaokui ; Ji, Zhongying ; Mao, Bigang ; Peng, Yan ; Shao, Ye ; Zhao, Bingran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-a11904aec9c8e52a14ce0ff3c791eb469cb3f2525728f848d9947f6a4f71fce83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biological Transport</topic><topic>cadmium</topic><topic>Cadmium - metabolism</topic><topic>Cadmium toxicity</topic><topic>environment</topic><topic>Manganese</topic><topic>Manganese - metabolism</topic><topic>Membrane Transport Proteins - genetics</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Membrane Transport Proteins - pharmacology</topic><topic>Metal transporter</topic><topic>mutation</topic><topic>Oryza - metabolism</topic><topic>OsNRAMP5</topic><topic>Plant Roots - metabolism</topic><topic>rice</topic><topic>Rice (Oryza sativa L.)</topic><topic>risk</topic><topic>toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Li</creatorcontrib><creatorcontrib>Dong, Jiayu</creatorcontrib><creatorcontrib>Qu, Mengmeng</creatorcontrib><creatorcontrib>Lv, Qiming</creatorcontrib><creatorcontrib>Zhang, Liping</creatorcontrib><creatorcontrib>Peng, Can</creatorcontrib><creatorcontrib>Hu, Yuanyi</creatorcontrib><creatorcontrib>Li, Yaokui</creatorcontrib><creatorcontrib>Ji, Zhongying</creatorcontrib><creatorcontrib>Mao, Bigang</creatorcontrib><creatorcontrib>Peng, Yan</creatorcontrib><creatorcontrib>Shao, Ye</creatorcontrib><creatorcontrib>Zhao, Bingran</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>The Science of the total environment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Li</au><au>Dong, Jiayu</au><au>Qu, Mengmeng</au><au>Lv, Qiming</au><au>Zhang, Liping</au><au>Peng, Can</au><au>Hu, Yuanyi</au><au>Li, Yaokui</au><au>Ji, Zhongying</au><au>Mao, Bigang</au><au>Peng, Yan</au><au>Shao, Ye</au><au>Zhao, Bingran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms</atitle><jtitle>The Science of the total environment</jtitle><addtitle>Sci Total Environ</addtitle><date>2022-08-01</date><risdate>2022</risdate><volume>832</volume><spage>155006</spage><epage>155006</epage><pages>155006-155006</pages><artnum>155006</artnum><issn>0048-9697</issn><eissn>1879-1026</eissn><abstract>OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.
[Display omitted]
•Knockout of OsNRAMP5 confers cadmium (Cd) tolerance of rice in a wide range of external Cd concentrations.•Knockout of OsNRAMP5 decreases Cd uptake but simultaneously facilitates Cd translocation from roots to shoots.•The impact of OsNRAMP5 knockout on Cd accumulation in above-ground tissues depends on external Cd concentrations.•Knockout of OsNRAMP5 complements deficient minerals in shoots, indirectly enhancing rice tolerance to severe Cd stress.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>35381246</pmid><doi>10.1016/j.scitotenv.2022.155006</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0048-9697 |
ispartof | The Science of the total environment, 2022-08, Vol.832, p.155006-155006, Article 155006 |
issn | 0048-9697 1879-1026 |
language | eng |
recordid | cdi_proquest_miscellaneous_2660998927 |
source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | Biological Transport cadmium Cadmium - metabolism Cadmium toxicity environment Manganese Manganese - metabolism Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism Membrane Transport Proteins - pharmacology Metal transporter mutation Oryza - metabolism OsNRAMP5 Plant Roots - metabolism rice Rice (Oryza sativa L.) risk toxicity |
title | Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T22%3A47%3A14IST&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=Knockout%20of%20OsNRAMP5%20enhances%20rice%20tolerance%20to%20cadmium%20toxicity%20in%20response%20to%20varying%20external%20cadmium%20concentrations%20via%20distinct%20mechanisms&rft.jtitle=The%20Science%20of%20the%20total%20environment&rft.au=Tang,%20Li&rft.date=2022-08-01&rft.volume=832&rft.spage=155006&rft.epage=155006&rft.pages=155006-155006&rft.artnum=155006&rft.issn=0048-9697&rft.eissn=1879-1026&rft_id=info:doi/10.1016/j.scitotenv.2022.155006&rft_dat=%3Cproquest_cross%3E2647654326%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=2647654326&rft_id=info:pmid/35381246&rft_els_id=S004896972202099X&rfr_iscdi=true |