ETS1 Ameliorates Hyperoxia-Induced Bronchopulmonary Dysplasia in Mice by Activating Nrf2/HO-1 Mediated Ferroptosis
Purpose Bronchopulmonary dysplasia (BPD) is associated with hyperoxia-induced oxidative stress-associated ferroptosis. This study examined the effect of E26 oncogene homolog 1 (ETS1) on oxidative stress-associated ferroptosis in BPD. Methods Hyperoxia-induced A549 cells and neonatal mice were used t...
Gespeichert in:
| Veröffentlicht in: | Lung 2023-08, Vol.201 (4), p.425-441 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 441 |
|---|---|
| container_issue | 4 |
| container_start_page | 425 |
| container_title | Lung |
| container_volume | 201 |
| creator | Yang, Min Chen, Yanping Huang, Xueshan Shen, Fang Meng, Yanni |
| description | Purpose
Bronchopulmonary dysplasia (BPD) is associated with hyperoxia-induced oxidative stress-associated ferroptosis. This study examined the effect of E26 oncogene homolog 1 (ETS1) on oxidative stress-associated ferroptosis in BPD.
Methods
Hyperoxia-induced A549 cells and neonatal mice were used to establish BPD models. The effects of ETS1 on hyperoxia-induced ferroptosis-like changes in A549 cells were investigated by overexpression of ETS1 plasmid transfection and erastin treatment. Glucose consumption, lactate production, and NADPH levels were assessed by the glucose, lactate, and NADP
+
/NADPH assay kits, respectively. The potential regulatory relationship between ETS1 and Nrf2/HO-1 was examined by treating hyperoxia-induced A549 cells with the Nrf2 inhibitor ML385. ETS1 effect on the Nrf2 promoter was explored by dual-luciferase reporter and chromatin immunoprecipitation assay. The effect of ETS1 on the symptoms of BPD mice was examined by injecting an adenovirus overexpressing ETS1.
Results
ETS1 overexpression increased hyperoxia-induced cell viability, glucose consumption, lactate production, and NADPH levels and reduced inflammation and apoptosis in A549 cells. In animal experiments, ETS1 overexpression prevented weight loss, airway enlargement, and reductions in radial alveolar counts in BPD mice, while reducing the mean linear intercept, mean alveolar diameter and inflammation. ETS1 overexpression suppressed PTGS2 and CHAC1 expression, reduced ROS, MDA and ferrous iron (Fe
2+
) production and increased GSH levels in hyperoxia-induced A549 cells and BPD mice. In addition, ETS1 can bind to the Nrf2 promoter region and thus promote Nrf2 transcription. ETS1 overexpression increased the mRNA and protein levels of Nrf2, HO-1, xCT, and GPX4 in hyperoxia-induced A549 cells and BPD mice. In hyperoxia-induced A549 cells, erastin and ML385 treatment abolished the effect of ETS1 overexpression.
Conclusion
ETS1 is important in oxidative stress-related ferroptosis in a hyperoxia-induced BPD model, and the effect is partially mediated by the Nrf2/HO-1 axis. |
| doi_str_mv | 10.1007/s00408-023-00639-1 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10444662</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A761884350</galeid><sourcerecordid>A761884350</sourcerecordid><originalsourceid>FETCH-LOGICAL-c611t-99806afac147038b23006c2f5d471e49d7aef2d9c71af6485c9ef2ee32af08733</originalsourceid><addsrcrecordid>eNp9kl9vFCEUxSdGY9fqF_DBkJgYX2j5NwPzZNbauk1a-2B9JixzZ5dmBkaYadxvL3Vr2zUbwwMBfudwuZyieEvJESVEHidCBFGYMI4JqXiN6bNiRgVnmMqSPC9mhAuKWYYOilcp3RBCZUXLl8UBl6LOEjEr4un1d4rmPXQuRDNCQovNADH8cgaf-2ay0KDPMXi7DsPU9cGbuEFfNmnoTHIGOY8unQW03KC5Hd2tGZ1foW-xZceLK0zRJTQuuzboDGIMwxiSS6-LF63pEry5nw-LH2en1ycLfHH19fxkfoFtRemI61qRyrTGUiEJV0vGc8WWtWUjJAVRN9JAy5raSmraSqjS1nkNwJlpiZKcHxaftr7DtOyhseDHaDo9RNfnR-hgnN498W6tV-FWUyKEqCqWHT7eO8Twc4I06t4lC11nPIQpaaYEVYqWqsro-3_QmzBFn9-XqbIkteRl-UitTAfa-Tbki-2dqZ7nr1FK8JJkCu-hVuAhVxk8tC5v7_BHe_g8Guid3Sv48ESwBtON6xS6aXTBp12QbUEbQ0oR2ofuUaLvMqi3GdQ5g_pPBjXNondP-_4g-Ru6DPAtkPKRX0F87NV_bH8D_nbksQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2855097355</pqid></control><display><type>article</type><title>ETS1 Ameliorates Hyperoxia-Induced Bronchopulmonary Dysplasia in Mice by Activating Nrf2/HO-1 Mediated Ferroptosis</title><source>SpringerLink Journals - AutoHoldings</source><creator>Yang, Min ; Chen, Yanping ; Huang, Xueshan ; Shen, Fang ; Meng, Yanni</creator><creatorcontrib>Yang, Min ; Chen, Yanping ; Huang, Xueshan ; Shen, Fang ; Meng, Yanni</creatorcontrib><description>Purpose
Bronchopulmonary dysplasia (BPD) is associated with hyperoxia-induced oxidative stress-associated ferroptosis. This study examined the effect of E26 oncogene homolog 1 (ETS1) on oxidative stress-associated ferroptosis in BPD.
Methods
Hyperoxia-induced A549 cells and neonatal mice were used to establish BPD models. The effects of ETS1 on hyperoxia-induced ferroptosis-like changes in A549 cells were investigated by overexpression of ETS1 plasmid transfection and erastin treatment. Glucose consumption, lactate production, and NADPH levels were assessed by the glucose, lactate, and NADP
+
/NADPH assay kits, respectively. The potential regulatory relationship between ETS1 and Nrf2/HO-1 was examined by treating hyperoxia-induced A549 cells with the Nrf2 inhibitor ML385. ETS1 effect on the Nrf2 promoter was explored by dual-luciferase reporter and chromatin immunoprecipitation assay. The effect of ETS1 on the symptoms of BPD mice was examined by injecting an adenovirus overexpressing ETS1.
Results
ETS1 overexpression increased hyperoxia-induced cell viability, glucose consumption, lactate production, and NADPH levels and reduced inflammation and apoptosis in A549 cells. In animal experiments, ETS1 overexpression prevented weight loss, airway enlargement, and reductions in radial alveolar counts in BPD mice, while reducing the mean linear intercept, mean alveolar diameter and inflammation. ETS1 overexpression suppressed PTGS2 and CHAC1 expression, reduced ROS, MDA and ferrous iron (Fe
2+
) production and increased GSH levels in hyperoxia-induced A549 cells and BPD mice. In addition, ETS1 can bind to the Nrf2 promoter region and thus promote Nrf2 transcription. ETS1 overexpression increased the mRNA and protein levels of Nrf2, HO-1, xCT, and GPX4 in hyperoxia-induced A549 cells and BPD mice. In hyperoxia-induced A549 cells, erastin and ML385 treatment abolished the effect of ETS1 overexpression.
Conclusion
ETS1 is important in oxidative stress-related ferroptosis in a hyperoxia-induced BPD model, and the effect is partially mediated by the Nrf2/HO-1 axis.</description><identifier>ISSN: 0341-2040</identifier><identifier>EISSN: 1432-1750</identifier><identifier>DOI: 10.1007/s00408-023-00639-1</identifier><identifier>PMID: 37490064</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Alveoli ; Analysis ; Animal experimentation ; Animal research ; Apoptosis ; Aurothioglucose ; Bronchopulmonary Dysplasia ; Cell viability ; Chromatin ; Consumption ; Dextrose ; Dysplasia ; Ets-1 protein ; Ferroptosis ; Glucose ; Hyperoxia ; Immunoprecipitation ; Inflammation ; Lactates ; Lactic acid ; Lung diseases ; Medicine ; Medicine & Public Health ; Neonates ; NRF2 protein ; Oxidative stress ; Pneumology/Respiratory System ; Transfection ; Weight loss</subject><ispartof>Lung, 2023-08, Vol.201 (4), p.425-441</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>COPYRIGHT 2023 Springer</rights><rights>The Author(s) 2023. 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-c611t-99806afac147038b23006c2f5d471e49d7aef2d9c71af6485c9ef2ee32af08733</citedby><cites>FETCH-LOGICAL-c611t-99806afac147038b23006c2f5d471e49d7aef2d9c71af6485c9ef2ee32af08733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00408-023-00639-1$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00408-023-00639-1$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37490064$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Min</creatorcontrib><creatorcontrib>Chen, Yanping</creatorcontrib><creatorcontrib>Huang, Xueshan</creatorcontrib><creatorcontrib>Shen, Fang</creatorcontrib><creatorcontrib>Meng, Yanni</creatorcontrib><title>ETS1 Ameliorates Hyperoxia-Induced Bronchopulmonary Dysplasia in Mice by Activating Nrf2/HO-1 Mediated Ferroptosis</title><title>Lung</title><addtitle>Lung</addtitle><addtitle>Lung</addtitle><description>Purpose
Bronchopulmonary dysplasia (BPD) is associated with hyperoxia-induced oxidative stress-associated ferroptosis. This study examined the effect of E26 oncogene homolog 1 (ETS1) on oxidative stress-associated ferroptosis in BPD.
Methods
Hyperoxia-induced A549 cells and neonatal mice were used to establish BPD models. The effects of ETS1 on hyperoxia-induced ferroptosis-like changes in A549 cells were investigated by overexpression of ETS1 plasmid transfection and erastin treatment. Glucose consumption, lactate production, and NADPH levels were assessed by the glucose, lactate, and NADP
+
/NADPH assay kits, respectively. The potential regulatory relationship between ETS1 and Nrf2/HO-1 was examined by treating hyperoxia-induced A549 cells with the Nrf2 inhibitor ML385. ETS1 effect on the Nrf2 promoter was explored by dual-luciferase reporter and chromatin immunoprecipitation assay. The effect of ETS1 on the symptoms of BPD mice was examined by injecting an adenovirus overexpressing ETS1.
Results
ETS1 overexpression increased hyperoxia-induced cell viability, glucose consumption, lactate production, and NADPH levels and reduced inflammation and apoptosis in A549 cells. In animal experiments, ETS1 overexpression prevented weight loss, airway enlargement, and reductions in radial alveolar counts in BPD mice, while reducing the mean linear intercept, mean alveolar diameter and inflammation. ETS1 overexpression suppressed PTGS2 and CHAC1 expression, reduced ROS, MDA and ferrous iron (Fe
2+
) production and increased GSH levels in hyperoxia-induced A549 cells and BPD mice. In addition, ETS1 can bind to the Nrf2 promoter region and thus promote Nrf2 transcription. ETS1 overexpression increased the mRNA and protein levels of Nrf2, HO-1, xCT, and GPX4 in hyperoxia-induced A549 cells and BPD mice. In hyperoxia-induced A549 cells, erastin and ML385 treatment abolished the effect of ETS1 overexpression.
Conclusion
ETS1 is important in oxidative stress-related ferroptosis in a hyperoxia-induced BPD model, and the effect is partially mediated by the Nrf2/HO-1 axis.</description><subject>Alveoli</subject><subject>Analysis</subject><subject>Animal experimentation</subject><subject>Animal research</subject><subject>Apoptosis</subject><subject>Aurothioglucose</subject><subject>Bronchopulmonary Dysplasia</subject><subject>Cell viability</subject><subject>Chromatin</subject><subject>Consumption</subject><subject>Dextrose</subject><subject>Dysplasia</subject><subject>Ets-1 protein</subject><subject>Ferroptosis</subject><subject>Glucose</subject><subject>Hyperoxia</subject><subject>Immunoprecipitation</subject><subject>Inflammation</subject><subject>Lactates</subject><subject>Lactic acid</subject><subject>Lung diseases</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neonates</subject><subject>NRF2 protein</subject><subject>Oxidative stress</subject><subject>Pneumology/Respiratory System</subject><subject>Transfection</subject><subject>Weight loss</subject><issn>0341-2040</issn><issn>1432-1750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kl9vFCEUxSdGY9fqF_DBkJgYX2j5NwPzZNbauk1a-2B9JixzZ5dmBkaYadxvL3Vr2zUbwwMBfudwuZyieEvJESVEHidCBFGYMI4JqXiN6bNiRgVnmMqSPC9mhAuKWYYOilcp3RBCZUXLl8UBl6LOEjEr4un1d4rmPXQuRDNCQovNADH8cgaf-2ay0KDPMXi7DsPU9cGbuEFfNmnoTHIGOY8unQW03KC5Hd2tGZ1foW-xZceLK0zRJTQuuzboDGIMwxiSS6-LF63pEry5nw-LH2en1ycLfHH19fxkfoFtRemI61qRyrTGUiEJV0vGc8WWtWUjJAVRN9JAy5raSmraSqjS1nkNwJlpiZKcHxaftr7DtOyhseDHaDo9RNfnR-hgnN498W6tV-FWUyKEqCqWHT7eO8Twc4I06t4lC11nPIQpaaYEVYqWqsro-3_QmzBFn9-XqbIkteRl-UitTAfa-Tbki-2dqZ7nr1FK8JJkCu-hVuAhVxk8tC5v7_BHe_g8Guid3Sv48ESwBtON6xS6aXTBp12QbUEbQ0oR2ofuUaLvMqi3GdQ5g_pPBjXNondP-_4g-Ru6DPAtkPKRX0F87NV_bH8D_nbksQ</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Yang, Min</creator><creator>Chen, Yanping</creator><creator>Huang, Xueshan</creator><creator>Shen, Fang</creator><creator>Meng, Yanni</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230801</creationdate><title>ETS1 Ameliorates Hyperoxia-Induced Bronchopulmonary Dysplasia in Mice by Activating Nrf2/HO-1 Mediated Ferroptosis</title><author>Yang, Min ; Chen, Yanping ; Huang, Xueshan ; Shen, Fang ; Meng, Yanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c611t-99806afac147038b23006c2f5d471e49d7aef2d9c71af6485c9ef2ee32af08733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alveoli</topic><topic>Analysis</topic><topic>Animal experimentation</topic><topic>Animal research</topic><topic>Apoptosis</topic><topic>Aurothioglucose</topic><topic>Bronchopulmonary Dysplasia</topic><topic>Cell viability</topic><topic>Chromatin</topic><topic>Consumption</topic><topic>Dextrose</topic><topic>Dysplasia</topic><topic>Ets-1 protein</topic><topic>Ferroptosis</topic><topic>Glucose</topic><topic>Hyperoxia</topic><topic>Immunoprecipitation</topic><topic>Inflammation</topic><topic>Lactates</topic><topic>Lactic acid</topic><topic>Lung diseases</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neonates</topic><topic>NRF2 protein</topic><topic>Oxidative stress</topic><topic>Pneumology/Respiratory System</topic><topic>Transfection</topic><topic>Weight loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Min</creatorcontrib><creatorcontrib>Chen, Yanping</creatorcontrib><creatorcontrib>Huang, Xueshan</creatorcontrib><creatorcontrib>Shen, Fang</creatorcontrib><creatorcontrib>Meng, Yanni</creatorcontrib><collection>SpringerOpen</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Lung</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Min</au><au>Chen, Yanping</au><au>Huang, Xueshan</au><au>Shen, Fang</au><au>Meng, Yanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ETS1 Ameliorates Hyperoxia-Induced Bronchopulmonary Dysplasia in Mice by Activating Nrf2/HO-1 Mediated Ferroptosis</atitle><jtitle>Lung</jtitle><stitle>Lung</stitle><addtitle>Lung</addtitle><date>2023-08-01</date><risdate>2023</risdate><volume>201</volume><issue>4</issue><spage>425</spage><epage>441</epage><pages>425-441</pages><issn>0341-2040</issn><eissn>1432-1750</eissn><abstract>Purpose
Bronchopulmonary dysplasia (BPD) is associated with hyperoxia-induced oxidative stress-associated ferroptosis. This study examined the effect of E26 oncogene homolog 1 (ETS1) on oxidative stress-associated ferroptosis in BPD.
Methods
Hyperoxia-induced A549 cells and neonatal mice were used to establish BPD models. The effects of ETS1 on hyperoxia-induced ferroptosis-like changes in A549 cells were investigated by overexpression of ETS1 plasmid transfection and erastin treatment. Glucose consumption, lactate production, and NADPH levels were assessed by the glucose, lactate, and NADP
+
/NADPH assay kits, respectively. The potential regulatory relationship between ETS1 and Nrf2/HO-1 was examined by treating hyperoxia-induced A549 cells with the Nrf2 inhibitor ML385. ETS1 effect on the Nrf2 promoter was explored by dual-luciferase reporter and chromatin immunoprecipitation assay. The effect of ETS1 on the symptoms of BPD mice was examined by injecting an adenovirus overexpressing ETS1.
Results
ETS1 overexpression increased hyperoxia-induced cell viability, glucose consumption, lactate production, and NADPH levels and reduced inflammation and apoptosis in A549 cells. In animal experiments, ETS1 overexpression prevented weight loss, airway enlargement, and reductions in radial alveolar counts in BPD mice, while reducing the mean linear intercept, mean alveolar diameter and inflammation. ETS1 overexpression suppressed PTGS2 and CHAC1 expression, reduced ROS, MDA and ferrous iron (Fe
2+
) production and increased GSH levels in hyperoxia-induced A549 cells and BPD mice. In addition, ETS1 can bind to the Nrf2 promoter region and thus promote Nrf2 transcription. ETS1 overexpression increased the mRNA and protein levels of Nrf2, HO-1, xCT, and GPX4 in hyperoxia-induced A549 cells and BPD mice. In hyperoxia-induced A549 cells, erastin and ML385 treatment abolished the effect of ETS1 overexpression.
Conclusion
ETS1 is important in oxidative stress-related ferroptosis in a hyperoxia-induced BPD model, and the effect is partially mediated by the Nrf2/HO-1 axis.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37490064</pmid><doi>10.1007/s00408-023-00639-1</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0341-2040 |
| ispartof | Lung, 2023-08, Vol.201 (4), p.425-441 |
| issn | 0341-2040 1432-1750 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10444662 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Alveoli Analysis Animal experimentation Animal research Apoptosis Aurothioglucose Bronchopulmonary Dysplasia Cell viability Chromatin Consumption Dextrose Dysplasia Ets-1 protein Ferroptosis Glucose Hyperoxia Immunoprecipitation Inflammation Lactates Lactic acid Lung diseases Medicine Medicine & Public Health Neonates NRF2 protein Oxidative stress Pneumology/Respiratory System Transfection Weight loss |
| title | ETS1 Ameliorates Hyperoxia-Induced Bronchopulmonary Dysplasia in Mice by Activating Nrf2/HO-1 Mediated Ferroptosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T17%3A18%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ETS1%20Ameliorates%20Hyperoxia-Induced%20Bronchopulmonary%20Dysplasia%20in%20Mice%20by%20Activating%20Nrf2/HO-1%20Mediated%20Ferroptosis&rft.jtitle=Lung&rft.au=Yang,%20Min&rft.date=2023-08-01&rft.volume=201&rft.issue=4&rft.spage=425&rft.epage=441&rft.pages=425-441&rft.issn=0341-2040&rft.eissn=1432-1750&rft_id=info:doi/10.1007/s00408-023-00639-1&rft_dat=%3Cgale_pubme%3EA761884350%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2855097355&rft_id=info:pmid/37490064&rft_galeid=A761884350&rfr_iscdi=true |