Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars

Pomegranate ( Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative difference...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Plant molecular biology 2024-06, Vol.114 (3), p.51-51, Article 51
Hauptverfasser: Zhao, Xueqing, Feng, Yingyi, Ke, Ding, Teng, Yingfen, Yuan, Zhaohe
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 51
container_issue 3
container_start_page 51
container_title Plant molecular biology
container_volume 114
creator Zhao, Xueqing
Feng, Yingyi
Ke, Ding
Teng, Yingfen
Yuan, Zhaohe
description Pomegranate ( Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate ‘Hongbaoshi’ and a purple-red-skinned cultivar ‘Moshiliu’, by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of ‘Hongbaoshi’ but high Dp in late stages of ‘Moshiliu’ were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of ‘Moshiliu’. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in ‘Moshiliu’ compared with ‘Hongbaoshi’. Alao, ANR was specially expressed in ‘Hongbaoshi’, with extremely low expression levels in ‘Moshiliu’. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYB s and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin ‘Moshiliu’. SG4 MYB s exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in ‘Moshiliu’ pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate. Key message Integrating metabolomic and transcriptomic data identified differentially anthocyanins, expressed structural genes and R2R3-MYB genes from SG4, SG5, and SG6, revealing the color variation in red and purple-red pomegranate.
doi_str_mv 10.1007/s11103-024-01446-9
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3050177628</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3050177628</sourcerecordid><originalsourceid>FETCH-LOGICAL-c359t-a80da086b89fc021e4e6d900e8f16184e0bce04823c9ff253f0944fc8e3c1e943</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhi1ERZfCH-CALHHhEjoTO459RCu-pEpc2rPldcaVqyQOdrKIf4_bLSBxgJNl-XmfGetl7BXCOwToLwsigmiglQ2glKoxT9gOu140HbT6KdsBqr6REttz9ryUO4AaE-oZOxdaGUTd79hxn6bFZbfGI_E1u7n4HJc1TdFzNw98otUd0vhwX3IKcaTCMx3JjTzkLa58IRq5r0jmR5djNaWZx5mv31MFB76kiW6r2K3E_TbWQS6XF-wsuLHQy8fzgt18_HC9_9xcff30Zf_-qvGiM2vjNAwOtDpoEzy0SJLUYABIB1SoJcHBE0jdCm9CaDsRwEgZvCbhkYwUF-ztyVt3_7ZRWe0Ui6dxdDOlrViBnVBSGdn9H4UOsO9Vqyv65i_0Lm15rh-plDRddRpTqfZE-ZxKyRTskuPk8g-LYO8LtKcCbS3QPhRo70OvH9XbYaLhd-RXYxUQJ6DUp_mW8p_Z_9D-BGYlp3Y</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3049553699</pqid></control><display><type>article</type><title>Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Zhao, Xueqing ; Feng, Yingyi ; Ke, Ding ; Teng, Yingfen ; Yuan, Zhaohe</creator><creatorcontrib>Zhao, Xueqing ; Feng, Yingyi ; Ke, Ding ; Teng, Yingfen ; Yuan, Zhaohe</creatorcontrib><description>Pomegranate ( Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate ‘Hongbaoshi’ and a purple-red-skinned cultivar ‘Moshiliu’, by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of ‘Hongbaoshi’ but high Dp in late stages of ‘Moshiliu’ were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of ‘Moshiliu’. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in ‘Moshiliu’ compared with ‘Hongbaoshi’. Alao, ANR was specially expressed in ‘Hongbaoshi’, with extremely low expression levels in ‘Moshiliu’. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYB s and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin ‘Moshiliu’. SG4 MYB s exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in ‘Moshiliu’ pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate. Key message Integrating metabolomic and transcriptomic data identified differentially anthocyanins, expressed structural genes and R2R3-MYB genes from SG4, SG5, and SG6, revealing the color variation in red and purple-red pomegranate.</description><identifier>ISSN: 0167-4412</identifier><identifier>ISSN: 1573-5028</identifier><identifier>EISSN: 1573-5028</identifier><identifier>DOI: 10.1007/s11103-024-01446-9</identifier><identifier>PMID: 38691187</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Anthocyanins ; Anthocyanins - genetics ; Anthocyanins - metabolism ; Biochemistry ; Biomedical and Life Sciences ; Color ; Cultivars ; cyanidin ; delphinidin ; Developmental stages ; family ; Fruit - genetics ; Fruit - metabolism ; fruit color ; Fruit crops ; Fruits ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Life Sciences ; Metabolomics ; Mutation ; pelargonidin ; phenotype ; Phenotypes ; Pigmentation - genetics ; Plant Pathology ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Plant Sciences ; Pomegranate - genetics ; Pomegranate - metabolism ; pomegranates ; Punica granatum ; Transcription factors ; Transcriptome ; Transcriptomics ; Variation</subject><ispartof>Plant molecular biology, 2024-06, Vol.114 (3), p.51-51, Article 51</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Nature B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c359t-a80da086b89fc021e4e6d900e8f16184e0bce04823c9ff253f0944fc8e3c1e943</cites><orcidid>0000-0003-1057-8458</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/s11103-024-01446-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11103-024-01446-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38691187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Xueqing</creatorcontrib><creatorcontrib>Feng, Yingyi</creatorcontrib><creatorcontrib>Ke, Ding</creatorcontrib><creatorcontrib>Teng, Yingfen</creatorcontrib><creatorcontrib>Yuan, Zhaohe</creatorcontrib><title>Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars</title><title>Plant molecular biology</title><addtitle>Plant Mol Biol</addtitle><addtitle>Plant Mol Biol</addtitle><description>Pomegranate ( Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate ‘Hongbaoshi’ and a purple-red-skinned cultivar ‘Moshiliu’, by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of ‘Hongbaoshi’ but high Dp in late stages of ‘Moshiliu’ were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of ‘Moshiliu’. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in ‘Moshiliu’ compared with ‘Hongbaoshi’. Alao, ANR was specially expressed in ‘Hongbaoshi’, with extremely low expression levels in ‘Moshiliu’. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYB s and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin ‘Moshiliu’. SG4 MYB s exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in ‘Moshiliu’ pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate. Key message Integrating metabolomic and transcriptomic data identified differentially anthocyanins, expressed structural genes and R2R3-MYB genes from SG4, SG5, and SG6, revealing the color variation in red and purple-red pomegranate.</description><subject>Anthocyanins</subject><subject>Anthocyanins - genetics</subject><subject>Anthocyanins - metabolism</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Color</subject><subject>Cultivars</subject><subject>cyanidin</subject><subject>delphinidin</subject><subject>Developmental stages</subject><subject>family</subject><subject>Fruit - genetics</subject><subject>Fruit - metabolism</subject><subject>fruit color</subject><subject>Fruit crops</subject><subject>Fruits</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Plant</subject><subject>Life Sciences</subject><subject>Metabolomics</subject><subject>Mutation</subject><subject>pelargonidin</subject><subject>phenotype</subject><subject>Phenotypes</subject><subject>Pigmentation - genetics</subject><subject>Plant Pathology</subject><subject>Plant Proteins - genetics</subject><subject>Plant Proteins - metabolism</subject><subject>Plant Sciences</subject><subject>Pomegranate - genetics</subject><subject>Pomegranate - metabolism</subject><subject>pomegranates</subject><subject>Punica granatum</subject><subject>Transcription factors</subject><subject>Transcriptome</subject><subject>Transcriptomics</subject><subject>Variation</subject><issn>0167-4412</issn><issn>1573-5028</issn><issn>1573-5028</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERZfCH-CALHHhEjoTO459RCu-pEpc2rPldcaVqyQOdrKIf4_bLSBxgJNl-XmfGetl7BXCOwToLwsigmiglQ2glKoxT9gOu140HbT6KdsBqr6REttz9ryUO4AaE-oZOxdaGUTd79hxn6bFZbfGI_E1u7n4HJc1TdFzNw98otUd0vhwX3IKcaTCMx3JjTzkLa58IRq5r0jmR5djNaWZx5mv31MFB76kiW6r2K3E_TbWQS6XF-wsuLHQy8fzgt18_HC9_9xcff30Zf_-qvGiM2vjNAwOtDpoEzy0SJLUYABIB1SoJcHBE0jdCm9CaDsRwEgZvCbhkYwUF-ztyVt3_7ZRWe0Ui6dxdDOlrViBnVBSGdn9H4UOsO9Vqyv65i_0Lm15rh-plDRddRpTqfZE-ZxKyRTskuPk8g-LYO8LtKcCbS3QPhRo70OvH9XbYaLhd-RXYxUQJ6DUp_mW8p_Z_9D-BGYlp3Y</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Zhao, Xueqing</creator><creator>Feng, Yingyi</creator><creator>Ke, Ding</creator><creator>Teng, Yingfen</creator><creator>Yuan, Zhaohe</creator><general>Springer Netherlands</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-1057-8458</orcidid></search><sort><creationdate>20240601</creationdate><title>Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars</title><author>Zhao, Xueqing ; Feng, Yingyi ; Ke, Ding ; Teng, Yingfen ; Yuan, Zhaohe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-a80da086b89fc021e4e6d900e8f16184e0bce04823c9ff253f0944fc8e3c1e943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Anthocyanins</topic><topic>Anthocyanins - genetics</topic><topic>Anthocyanins - metabolism</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Color</topic><topic>Cultivars</topic><topic>cyanidin</topic><topic>delphinidin</topic><topic>Developmental stages</topic><topic>family</topic><topic>Fruit - genetics</topic><topic>Fruit - metabolism</topic><topic>fruit color</topic><topic>Fruit crops</topic><topic>Fruits</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Plant</topic><topic>Life Sciences</topic><topic>Metabolomics</topic><topic>Mutation</topic><topic>pelargonidin</topic><topic>phenotype</topic><topic>Phenotypes</topic><topic>Pigmentation - genetics</topic><topic>Plant Pathology</topic><topic>Plant Proteins - genetics</topic><topic>Plant Proteins - metabolism</topic><topic>Plant Sciences</topic><topic>Pomegranate - genetics</topic><topic>Pomegranate - metabolism</topic><topic>pomegranates</topic><topic>Punica granatum</topic><topic>Transcription factors</topic><topic>Transcriptome</topic><topic>Transcriptomics</topic><topic>Variation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Xueqing</creatorcontrib><creatorcontrib>Feng, Yingyi</creatorcontrib><creatorcontrib>Ke, Ding</creatorcontrib><creatorcontrib>Teng, Yingfen</creatorcontrib><creatorcontrib>Yuan, Zhaohe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Plant molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Xueqing</au><au>Feng, Yingyi</au><au>Ke, Ding</au><au>Teng, Yingfen</au><au>Yuan, Zhaohe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars</atitle><jtitle>Plant molecular biology</jtitle><stitle>Plant Mol Biol</stitle><addtitle>Plant Mol Biol</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>114</volume><issue>3</issue><spage>51</spage><epage>51</epage><pages>51-51</pages><artnum>51</artnum><issn>0167-4412</issn><issn>1573-5028</issn><eissn>1573-5028</eissn><abstract>Pomegranate ( Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate ‘Hongbaoshi’ and a purple-red-skinned cultivar ‘Moshiliu’, by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of ‘Hongbaoshi’ but high Dp in late stages of ‘Moshiliu’ were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of ‘Moshiliu’. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in ‘Moshiliu’ compared with ‘Hongbaoshi’. Alao, ANR was specially expressed in ‘Hongbaoshi’, with extremely low expression levels in ‘Moshiliu’. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYB s and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin ‘Moshiliu’. SG4 MYB s exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in ‘Moshiliu’ pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate. Key message Integrating metabolomic and transcriptomic data identified differentially anthocyanins, expressed structural genes and R2R3-MYB genes from SG4, SG5, and SG6, revealing the color variation in red and purple-red pomegranate.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>38691187</pmid><doi>10.1007/s11103-024-01446-9</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-1057-8458</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0167-4412
ispartof Plant molecular biology, 2024-06, Vol.114 (3), p.51-51, Article 51
issn 0167-4412
1573-5028
1573-5028
language eng
recordid cdi_proquest_miscellaneous_3050177628
source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Anthocyanins
Anthocyanins - genetics
Anthocyanins - metabolism
Biochemistry
Biomedical and Life Sciences
Color
Cultivars
cyanidin
delphinidin
Developmental stages
family
Fruit - genetics
Fruit - metabolism
fruit color
Fruit crops
Fruits
Gene Expression Profiling
Gene Expression Regulation, Plant
Life Sciences
Metabolomics
Mutation
pelargonidin
phenotype
Phenotypes
Pigmentation - genetics
Plant Pathology
Plant Proteins - genetics
Plant Proteins - metabolism
Plant Sciences
Pomegranate - genetics
Pomegranate - metabolism
pomegranates
Punica granatum
Transcription factors
Transcriptome
Transcriptomics
Variation
title Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T17%3A01%3A28IST&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=Comparative%20transcriptomic%20and%20metabolomic%20profiles%20reveal%20fruit%20peel%20color%20variation%20in%20two%20red%20pomegranate%20cultivars&rft.jtitle=Plant%20molecular%20biology&rft.au=Zhao,%20Xueqing&rft.date=2024-06-01&rft.volume=114&rft.issue=3&rft.spage=51&rft.epage=51&rft.pages=51-51&rft.artnum=51&rft.issn=0167-4412&rft.eissn=1573-5028&rft_id=info:doi/10.1007/s11103-024-01446-9&rft_dat=%3Cproquest_cross%3E3050177628%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=3049553699&rft_id=info:pmid/38691187&rfr_iscdi=true