TaERF87 and TaAKS1 synergistically regulate TaP5CS1/TaP5CR1‐mediated proline biosynthesis to enhance drought tolerance in wheat
Summary Drought stress limits wheat production and threatens food security world‐wide. While ethylene‐responsive factors (ERFs) are known to regulate plant response to drought stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear. Here, we describe the positive regula...
Gespeichert in:
| Veröffentlicht in: | The New phytologist 2023-01, Vol.237 (1), p.232-250 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 250 |
|---|---|
| container_issue | 1 |
| container_start_page | 232 |
| container_title | The New phytologist |
| container_volume | 237 |
| creator | Du, Linying Huang, Xueling Ding, Li Wang, Zhongxue Tang, Dongling Chen, Bin Ao, Lanjiya Liu, Yuling Kang, Zhensheng Mao, Hude |
| description | Summary
Drought stress limits wheat production and threatens food security world‐wide. While ethylene‐responsive factors (ERFs) are known to regulate plant response to drought stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear.
Here, we describe the positive regulatory role of TaERF87 in mediating wheat tolerance to drought stress. TaERF87 overexpression (OE) enhances drought tolerance, while silencing leads to drought sensitivity in wheat. RNA sequencing with biochemical assays revealed that TaERF87 activates the expression of the proline biosynthesis genes TaP5CS1 and TaP5CR1 via direct binding to GCC‐box elements. Furthermore, proline accumulates to higher levels in TaERF87‐ and TaP5CS1‐OE lines than that in wild‐type plants under well‐watered and drought stress conditions concomitantly with enhanced drought tolerance in these transgenic lines.
Moreover, the interaction between TaERF87 and the bHLH transcription factor TaAKS1 synergistically enhances TaP5CS1 and TaP5CR1 transcriptional activation. TaAKS1 OE also increases wheat drought tolerance by promoting proline accumulation. Additionally, our findings verified that TaERF87 and TaAKS1 are targets of abscisic acid‐responsive element binding factor 2 (TaABF2).
Together, our study elucidates the mechanisms underlying a positive response to drought stress mediated by the TaABF2–TaERF87/TaAKS1–TaP5CS1/TaP5CR1 module, and identifies candidate genes for the development of elite drought‐tolerant wheat varieties. |
| doi_str_mv | 10.1111/nph.18549 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2726923701</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2726923701</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3539-dd67c9ccc99eac0ac19eede0459bb86564548bfa880f6a1444c6d7d3e3b3e7403</originalsourceid><addsrcrecordid>eNp1kc9OGzEQxq0KVALtoS9QWeIChyX-t971EUVQKlCLIJV6W3ntSdbI8QZ7Vyi38gY8Y5-kbkJ7qNS5jDTzm08z8yH0gZIzmmMa1t0ZrUuh3qAJFVIVNeXVHpoQwupCCvn9AB2m9EAIUaVkb9EBl0yKUpYT9DzXF3eXdYV1sHiuz6_vKU6bAHHp0uCM9n6DIyxHrwfI_dtydk-n23xHf_54WYF1uWPxOvbeBcCt6_P40EFyCQ89htDpYADb2I_LbsglD3FbcQE_daCHd2h_oX2C96_5CH27vJjProqbr58-z85vCsNLrgprZWWUMUYp0IZoQxWABSJK1ba1LPM9om4Xuq7JQmoqhDDSVpYDbzlUgvAjdLLTzas-jpCGZuWSAe91gH5MDauYVIxXhGb0-B_0oR9jyNtlKv-XMkZZpk53lIl9ShEWzTq6lY6bhpLmty9N9qXZ-pLZj6-KY5t_9pf8Y0QGpjvgyXnY_F-p-XJ7tZP8BW4GmDM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2746912212</pqid></control><display><type>article</type><title>TaERF87 and TaAKS1 synergistically regulate TaP5CS1/TaP5CR1‐mediated proline biosynthesis to enhance drought tolerance in wheat</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Du, Linying ; Huang, Xueling ; Ding, Li ; Wang, Zhongxue ; Tang, Dongling ; Chen, Bin ; Ao, Lanjiya ; Liu, Yuling ; Kang, Zhensheng ; Mao, Hude</creator><creatorcontrib>Du, Linying ; Huang, Xueling ; Ding, Li ; Wang, Zhongxue ; Tang, Dongling ; Chen, Bin ; Ao, Lanjiya ; Liu, Yuling ; Kang, Zhensheng ; Mao, Hude</creatorcontrib><description>Summary
Drought stress limits wheat production and threatens food security world‐wide. While ethylene‐responsive factors (ERFs) are known to regulate plant response to drought stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear.
Here, we describe the positive regulatory role of TaERF87 in mediating wheat tolerance to drought stress. TaERF87 overexpression (OE) enhances drought tolerance, while silencing leads to drought sensitivity in wheat. RNA sequencing with biochemical assays revealed that TaERF87 activates the expression of the proline biosynthesis genes TaP5CS1 and TaP5CR1 via direct binding to GCC‐box elements. Furthermore, proline accumulates to higher levels in TaERF87‐ and TaP5CS1‐OE lines than that in wild‐type plants under well‐watered and drought stress conditions concomitantly with enhanced drought tolerance in these transgenic lines.
Moreover, the interaction between TaERF87 and the bHLH transcription factor TaAKS1 synergistically enhances TaP5CS1 and TaP5CR1 transcriptional activation. TaAKS1 OE also increases wheat drought tolerance by promoting proline accumulation. Additionally, our findings verified that TaERF87 and TaAKS1 are targets of abscisic acid‐responsive element binding factor 2 (TaABF2).
Together, our study elucidates the mechanisms underlying a positive response to drought stress mediated by the TaABF2–TaERF87/TaAKS1–TaP5CS1/TaP5CR1 module, and identifies candidate genes for the development of elite drought‐tolerant wheat varieties.</description><identifier>ISSN: 0028-646X</identifier><identifier>EISSN: 1469-8137</identifier><identifier>DOI: 10.1111/nph.18549</identifier><identifier>PMID: 36264565</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Abscisic acid ; Binding ; Biosynthesis ; Crop production ; Drought ; Drought Resistance ; drought tolerance ; Droughts ; ERF transcription factor ; Food security ; Gene Expression Regulation, Plant ; Gene sequencing ; Genes ; Helix-loop-helix proteins (basic) ; Phenotypes ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Plants, Genetically Modified - metabolism ; Proline ; Proline - metabolism ; proline biosynthesis ; Regulatory mechanisms (biology) ; Regulatory sequences ; RNA sequencing ; Stress, Physiological - genetics ; TaAKS1 ; TaERF87 ; Transcription ; Transcription activation ; Triticum - metabolism ; Wheat</subject><ispartof>The New phytologist, 2023-01, Vol.237 (1), p.232-250</ispartof><rights>2022 The Authors. © 2022 New Phytologist Foundation.</rights><rights>2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.</rights><rights>Copyright © 2023 New Phytologist Trust</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3539-dd67c9ccc99eac0ac19eede0459bb86564548bfa880f6a1444c6d7d3e3b3e7403</citedby><cites>FETCH-LOGICAL-c3539-dd67c9ccc99eac0ac19eede0459bb86564548bfa880f6a1444c6d7d3e3b3e7403</cites><orcidid>0000-0002-2484-9952 ; 0000-0002-0921-7981 ; 0000-0003-3998-5575 ; 0000-0001-5575-0122 ; 0000-0003-0623-6164 ; 0000-0003-3585-3954</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fnph.18549$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fnph.18549$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,1432,27922,27923,45572,45573,46407,46831</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36264565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Du, Linying</creatorcontrib><creatorcontrib>Huang, Xueling</creatorcontrib><creatorcontrib>Ding, Li</creatorcontrib><creatorcontrib>Wang, Zhongxue</creatorcontrib><creatorcontrib>Tang, Dongling</creatorcontrib><creatorcontrib>Chen, Bin</creatorcontrib><creatorcontrib>Ao, Lanjiya</creatorcontrib><creatorcontrib>Liu, Yuling</creatorcontrib><creatorcontrib>Kang, Zhensheng</creatorcontrib><creatorcontrib>Mao, Hude</creatorcontrib><title>TaERF87 and TaAKS1 synergistically regulate TaP5CS1/TaP5CR1‐mediated proline biosynthesis to enhance drought tolerance in wheat</title><title>The New phytologist</title><addtitle>New Phytol</addtitle><description>Summary
Drought stress limits wheat production and threatens food security world‐wide. While ethylene‐responsive factors (ERFs) are known to regulate plant response to drought stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear.
Here, we describe the positive regulatory role of TaERF87 in mediating wheat tolerance to drought stress. TaERF87 overexpression (OE) enhances drought tolerance, while silencing leads to drought sensitivity in wheat. RNA sequencing with biochemical assays revealed that TaERF87 activates the expression of the proline biosynthesis genes TaP5CS1 and TaP5CR1 via direct binding to GCC‐box elements. Furthermore, proline accumulates to higher levels in TaERF87‐ and TaP5CS1‐OE lines than that in wild‐type plants under well‐watered and drought stress conditions concomitantly with enhanced drought tolerance in these transgenic lines.
Moreover, the interaction between TaERF87 and the bHLH transcription factor TaAKS1 synergistically enhances TaP5CS1 and TaP5CR1 transcriptional activation. TaAKS1 OE also increases wheat drought tolerance by promoting proline accumulation. Additionally, our findings verified that TaERF87 and TaAKS1 are targets of abscisic acid‐responsive element binding factor 2 (TaABF2).
Together, our study elucidates the mechanisms underlying a positive response to drought stress mediated by the TaABF2–TaERF87/TaAKS1–TaP5CS1/TaP5CR1 module, and identifies candidate genes for the development of elite drought‐tolerant wheat varieties.</description><subject>Abscisic acid</subject><subject>Binding</subject><subject>Biosynthesis</subject><subject>Crop production</subject><subject>Drought</subject><subject>Drought Resistance</subject><subject>drought tolerance</subject><subject>Droughts</subject><subject>ERF transcription factor</subject><subject>Food security</subject><subject>Gene Expression Regulation, Plant</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Helix-loop-helix proteins (basic)</subject><subject>Phenotypes</subject><subject>Plant Proteins - genetics</subject><subject>Plant Proteins - metabolism</subject><subject>Plants, Genetically Modified - metabolism</subject><subject>Proline</subject><subject>Proline - metabolism</subject><subject>proline biosynthesis</subject><subject>Regulatory mechanisms (biology)</subject><subject>Regulatory sequences</subject><subject>RNA sequencing</subject><subject>Stress, Physiological - genetics</subject><subject>TaAKS1</subject><subject>TaERF87</subject><subject>Transcription</subject><subject>Transcription activation</subject><subject>Triticum - metabolism</subject><subject>Wheat</subject><issn>0028-646X</issn><issn>1469-8137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9OGzEQxq0KVALtoS9QWeIChyX-t971EUVQKlCLIJV6W3ntSdbI8QZ7Vyi38gY8Y5-kbkJ7qNS5jDTzm08z8yH0gZIzmmMa1t0ZrUuh3qAJFVIVNeXVHpoQwupCCvn9AB2m9EAIUaVkb9EBl0yKUpYT9DzXF3eXdYV1sHiuz6_vKU6bAHHp0uCM9n6DIyxHrwfI_dtydk-n23xHf_54WYF1uWPxOvbeBcCt6_P40EFyCQ89htDpYADb2I_LbsglD3FbcQE_daCHd2h_oX2C96_5CH27vJjProqbr58-z85vCsNLrgprZWWUMUYp0IZoQxWABSJK1ba1LPM9om4Xuq7JQmoqhDDSVpYDbzlUgvAjdLLTzas-jpCGZuWSAe91gH5MDauYVIxXhGb0-B_0oR9jyNtlKv-XMkZZpk53lIl9ShEWzTq6lY6bhpLmty9N9qXZ-pLZj6-KY5t_9pf8Y0QGpjvgyXnY_F-p-XJ7tZP8BW4GmDM</recordid><startdate>202301</startdate><enddate>202301</enddate><creator>Du, Linying</creator><creator>Huang, Xueling</creator><creator>Ding, Li</creator><creator>Wang, Zhongxue</creator><creator>Tang, Dongling</creator><creator>Chen, Bin</creator><creator>Ao, Lanjiya</creator><creator>Liu, Yuling</creator><creator>Kang, Zhensheng</creator><creator>Mao, Hude</creator><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7SN</scope><scope>8FD</scope><scope>C1K</scope><scope>F1W</scope><scope>FR3</scope><scope>H95</scope><scope>L.G</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2484-9952</orcidid><orcidid>https://orcid.org/0000-0002-0921-7981</orcidid><orcidid>https://orcid.org/0000-0003-3998-5575</orcidid><orcidid>https://orcid.org/0000-0001-5575-0122</orcidid><orcidid>https://orcid.org/0000-0003-0623-6164</orcidid><orcidid>https://orcid.org/0000-0003-3585-3954</orcidid></search><sort><creationdate>202301</creationdate><title>TaERF87 and TaAKS1 synergistically regulate TaP5CS1/TaP5CR1‐mediated proline biosynthesis to enhance drought tolerance in wheat</title><author>Du, Linying ; Huang, Xueling ; Ding, Li ; Wang, Zhongxue ; Tang, Dongling ; Chen, Bin ; Ao, Lanjiya ; Liu, Yuling ; Kang, Zhensheng ; Mao, Hude</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3539-dd67c9ccc99eac0ac19eede0459bb86564548bfa880f6a1444c6d7d3e3b3e7403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Abscisic acid</topic><topic>Binding</topic><topic>Biosynthesis</topic><topic>Crop production</topic><topic>Drought</topic><topic>Drought Resistance</topic><topic>drought tolerance</topic><topic>Droughts</topic><topic>ERF transcription factor</topic><topic>Food security</topic><topic>Gene Expression Regulation, Plant</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Helix-loop-helix proteins (basic)</topic><topic>Phenotypes</topic><topic>Plant Proteins - genetics</topic><topic>Plant Proteins - metabolism</topic><topic>Plants, Genetically Modified - metabolism</topic><topic>Proline</topic><topic>Proline - metabolism</topic><topic>proline biosynthesis</topic><topic>Regulatory mechanisms (biology)</topic><topic>Regulatory sequences</topic><topic>RNA sequencing</topic><topic>Stress, Physiological - genetics</topic><topic>TaAKS1</topic><topic>TaERF87</topic><topic>Transcription</topic><topic>Transcription activation</topic><topic>Triticum - metabolism</topic><topic>Wheat</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Du, Linying</creatorcontrib><creatorcontrib>Huang, Xueling</creatorcontrib><creatorcontrib>Ding, Li</creatorcontrib><creatorcontrib>Wang, Zhongxue</creatorcontrib><creatorcontrib>Tang, Dongling</creatorcontrib><creatorcontrib>Chen, Bin</creatorcontrib><creatorcontrib>Ao, Lanjiya</creatorcontrib><creatorcontrib>Liu, Yuling</creatorcontrib><creatorcontrib>Kang, Zhensheng</creatorcontrib><creatorcontrib>Mao, Hude</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Ecology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The New phytologist</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Du, Linying</au><au>Huang, Xueling</au><au>Ding, Li</au><au>Wang, Zhongxue</au><au>Tang, Dongling</au><au>Chen, Bin</au><au>Ao, Lanjiya</au><au>Liu, Yuling</au><au>Kang, Zhensheng</au><au>Mao, Hude</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TaERF87 and TaAKS1 synergistically regulate TaP5CS1/TaP5CR1‐mediated proline biosynthesis to enhance drought tolerance in wheat</atitle><jtitle>The New phytologist</jtitle><addtitle>New Phytol</addtitle><date>2023-01</date><risdate>2023</risdate><volume>237</volume><issue>1</issue><spage>232</spage><epage>250</epage><pages>232-250</pages><issn>0028-646X</issn><eissn>1469-8137</eissn><abstract>Summary
Drought stress limits wheat production and threatens food security world‐wide. While ethylene‐responsive factors (ERFs) are known to regulate plant response to drought stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear.
Here, we describe the positive regulatory role of TaERF87 in mediating wheat tolerance to drought stress. TaERF87 overexpression (OE) enhances drought tolerance, while silencing leads to drought sensitivity in wheat. RNA sequencing with biochemical assays revealed that TaERF87 activates the expression of the proline biosynthesis genes TaP5CS1 and TaP5CR1 via direct binding to GCC‐box elements. Furthermore, proline accumulates to higher levels in TaERF87‐ and TaP5CS1‐OE lines than that in wild‐type plants under well‐watered and drought stress conditions concomitantly with enhanced drought tolerance in these transgenic lines.
Moreover, the interaction between TaERF87 and the bHLH transcription factor TaAKS1 synergistically enhances TaP5CS1 and TaP5CR1 transcriptional activation. TaAKS1 OE also increases wheat drought tolerance by promoting proline accumulation. Additionally, our findings verified that TaERF87 and TaAKS1 are targets of abscisic acid‐responsive element binding factor 2 (TaABF2).
Together, our study elucidates the mechanisms underlying a positive response to drought stress mediated by the TaABF2–TaERF87/TaAKS1–TaP5CS1/TaP5CR1 module, and identifies candidate genes for the development of elite drought‐tolerant wheat varieties.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36264565</pmid><doi>10.1111/nph.18549</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-2484-9952</orcidid><orcidid>https://orcid.org/0000-0002-0921-7981</orcidid><orcidid>https://orcid.org/0000-0003-3998-5575</orcidid><orcidid>https://orcid.org/0000-0001-5575-0122</orcidid><orcidid>https://orcid.org/0000-0003-0623-6164</orcidid><orcidid>https://orcid.org/0000-0003-3585-3954</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-646X |
| ispartof | The New phytologist, 2023-01, Vol.237 (1), p.232-250 |
| issn | 0028-646X 1469-8137 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2726923701 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Free Content; EZB-FREE-00999 freely available EZB journals |
| subjects | Abscisic acid Binding Biosynthesis Crop production Drought Drought Resistance drought tolerance Droughts ERF transcription factor Food security Gene Expression Regulation, Plant Gene sequencing Genes Helix-loop-helix proteins (basic) Phenotypes Plant Proteins - genetics Plant Proteins - metabolism Plants, Genetically Modified - metabolism Proline Proline - metabolism proline biosynthesis Regulatory mechanisms (biology) Regulatory sequences RNA sequencing Stress, Physiological - genetics TaAKS1 TaERF87 Transcription Transcription activation Triticum - metabolism Wheat |
| title | TaERF87 and TaAKS1 synergistically regulate TaP5CS1/TaP5CR1‐mediated proline biosynthesis to enhance drought tolerance in wheat |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T12%3A28%3A38IST&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=TaERF87%20and%20TaAKS1%20synergistically%20regulate%20TaP5CS1/TaP5CR1%E2%80%90mediated%20proline%20biosynthesis%20to%20enhance%20drought%20tolerance%20in%20wheat&rft.jtitle=The%20New%20phytologist&rft.au=Du,%20Linying&rft.date=2023-01&rft.volume=237&rft.issue=1&rft.spage=232&rft.epage=250&rft.pages=232-250&rft.issn=0028-646X&rft.eissn=1469-8137&rft_id=info:doi/10.1111/nph.18549&rft_dat=%3Cproquest_cross%3E2726923701%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=2746912212&rft_id=info:pmid/36264565&rfr_iscdi=true |