Loading…
A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome
Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic Limosilactobacillus fermentum GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-...
Saved in:
| Published in: | NPJ science of food 2024-09, Vol.8 (1), p.61-16, Article 61 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | cdi_FETCH-LOGICAL-c366t-d5e61b2b367c1c79de381fda13888bf775f1946cdac1d13fb7dcd8f37821b3973 |
| container_end_page | 16 |
| container_issue | 1 |
| container_start_page | 61 |
| container_title | NPJ science of food |
| container_volume | 8 |
| creator | Zhou, Tuoyu Wu, Jingyuan Khan, Aman Hu, Tianxiang Wang, Yiqing Salama, El-Sayed Su, Shaochen Han, Huawen Jin, Weilin Li, Xiangkai |
| description | Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic
Limosilactobacillus fermentum
GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer
Lachnospiraceae
NK4A136 group and suppressing pro-inflammatory strain
Bacteroides
. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (
xseA
,
ALDH
) and butyrate synthesis gene (
bcd
), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation. |
| doi_str_mv | 10.1038/s41538-024-00307-5 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_6ea069d85824446c8c1535d381052e44</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_6ea069d85824446c8c1535d381052e44</doaj_id><sourcerecordid>3101378153</sourcerecordid><originalsourceid>FETCH-LOGICAL-c366t-d5e61b2b367c1c79de381fda13888bf775f1946cdac1d13fb7dcd8f37821b3973</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhSMEolXpC3SBLLFhY_BPHDvLqoK20pWQEF1bjj2JfJXExU6QWPHqTJO2IBasPBp_Pmc8p6ouOPvAmTQfS82VNJSJmjImmabqRXUqZNtQIzV7-Vd9Up2XcmSMCV4zxfTr6kS2ohaqMafVr0tyn1MX0xI9OcQplTg6v6TO-TiOayE95AnmZZ3I9VcqyRSXOLgFCvFpxLpQV0ryEVuBIJVyHGCGEguJM9IeyI_oyJTCOrolzgMZ1uWhv5lO8KZ61buxwPnjeVbdff707eqGHr5c315dHqiXTbPQoKDhnehkoz33ug0gDe-D49IY0_Vaq563deOD8zxw2Xc6-GB6qY3gnWy1PKtud92Q3NHe5zi5_NMmF-3WSHmwLuMORrANONa0wSgj6ho1jcdNq4CGTAmoa9R6v2vh5r6vUBY7xeJhHN0MaS1WcsZ1q8Rm--4f9JjWPONPNwrnQ22kxE7hVkrJ0D8PyJl9SNvuaVtM225pW4WP3j5Kr90E4fnJU7YIyB0oeDUPkP94_0f2N5zDtY4</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3101378153</pqid></control><display><type>article</type><title>A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Zhou, Tuoyu ; Wu, Jingyuan ; Khan, Aman ; Hu, Tianxiang ; Wang, Yiqing ; Salama, El-Sayed ; Su, Shaochen ; Han, Huawen ; Jin, Weilin ; Li, Xiangkai</creator><creatorcontrib>Zhou, Tuoyu ; Wu, Jingyuan ; Khan, Aman ; Hu, Tianxiang ; Wang, Yiqing ; Salama, El-Sayed ; Su, Shaochen ; Han, Huawen ; Jin, Weilin ; Li, Xiangkai</creatorcontrib><description>Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic
Limosilactobacillus fermentum
GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer
Lachnospiraceae
NK4A136 group and suppressing pro-inflammatory strain
Bacteroides
. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (
xseA
,
ALDH
) and butyrate synthesis gene (
bcd
), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation.</description><identifier>ISSN: 2396-8370</identifier><identifier>EISSN: 2396-8370</identifier><identifier>DOI: 10.1038/s41538-024-00307-5</identifier><identifier>PMID: 39242568</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/326/2565/2134 ; 631/326/41/2533 ; 631/67/1504 ; Acids ; Antioxidants ; Apoptosis ; Ascorbic acid ; Bile acids ; Cancer therapies ; Chemistry ; Chemistry and Materials Science ; Chemistry/Food Science ; Colitis ; Colon ; Colorectal cancer ; Colorectal carcinoma ; Digestive system ; Fermented food ; Food ; Food Microbiology ; Food Science ; Gastrointestinal tract ; Indoles ; Inflammatory bowel disease ; Intestinal microflora ; Limosilactobacillus fermentum ; Metabolites ; Metagenomics ; Microbiomes ; Microbiota ; Nutrition ; Oxidative stress ; Probiotics ; Radiation therapy ; Strain analysis ; Surgery ; Traditional foods ; Tumorigenesis ; Vitamin C ; Weight loss</subject><ispartof>NPJ science of food, 2024-09, Vol.8 (1), p.61-16, Article 61</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/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><cites>FETCH-LOGICAL-c366t-d5e61b2b367c1c79de381fda13888bf775f1946cdac1d13fb7dcd8f37821b3973</cites><orcidid>0000-0003-2931-7565</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/3101378153?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25752,27923,27924,37011,37012,44589</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39242568$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Tuoyu</creatorcontrib><creatorcontrib>Wu, Jingyuan</creatorcontrib><creatorcontrib>Khan, Aman</creatorcontrib><creatorcontrib>Hu, Tianxiang</creatorcontrib><creatorcontrib>Wang, Yiqing</creatorcontrib><creatorcontrib>Salama, El-Sayed</creatorcontrib><creatorcontrib>Su, Shaochen</creatorcontrib><creatorcontrib>Han, Huawen</creatorcontrib><creatorcontrib>Jin, Weilin</creatorcontrib><creatorcontrib>Li, Xiangkai</creatorcontrib><title>A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome</title><title>NPJ science of food</title><addtitle>npj Sci Food</addtitle><addtitle>NPJ Sci Food</addtitle><description>Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic
Limosilactobacillus fermentum
GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer
Lachnospiraceae
NK4A136 group and suppressing pro-inflammatory strain
Bacteroides
. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (
xseA
,
ALDH
) and butyrate synthesis gene (
bcd
), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation.</description><subject>631/326/2565/2134</subject><subject>631/326/41/2533</subject><subject>631/67/1504</subject><subject>Acids</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Ascorbic acid</subject><subject>Bile acids</subject><subject>Cancer therapies</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chemistry/Food Science</subject><subject>Colitis</subject><subject>Colon</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Digestive system</subject><subject>Fermented food</subject><subject>Food</subject><subject>Food Microbiology</subject><subject>Food Science</subject><subject>Gastrointestinal tract</subject><subject>Indoles</subject><subject>Inflammatory bowel disease</subject><subject>Intestinal microflora</subject><subject>Limosilactobacillus fermentum</subject><subject>Metabolites</subject><subject>Metagenomics</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Nutrition</subject><subject>Oxidative stress</subject><subject>Probiotics</subject><subject>Radiation therapy</subject><subject>Strain analysis</subject><subject>Surgery</subject><subject>Traditional foods</subject><subject>Tumorigenesis</subject><subject>Vitamin C</subject><subject>Weight loss</subject><issn>2396-8370</issn><issn>2396-8370</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kc1u1TAQhSMEolXpC3SBLLFhY_BPHDvLqoK20pWQEF1bjj2JfJXExU6QWPHqTJO2IBasPBp_Pmc8p6ouOPvAmTQfS82VNJSJmjImmabqRXUqZNtQIzV7-Vd9Up2XcmSMCV4zxfTr6kS2ohaqMafVr0tyn1MX0xI9OcQplTg6v6TO-TiOayE95AnmZZ3I9VcqyRSXOLgFCvFpxLpQV0ryEVuBIJVyHGCGEguJM9IeyI_oyJTCOrolzgMZ1uWhv5lO8KZ61buxwPnjeVbdff707eqGHr5c315dHqiXTbPQoKDhnehkoz33ug0gDe-D49IY0_Vaq563deOD8zxw2Xc6-GB6qY3gnWy1PKtud92Q3NHe5zi5_NMmF-3WSHmwLuMORrANONa0wSgj6ho1jcdNq4CGTAmoa9R6v2vh5r6vUBY7xeJhHN0MaS1WcsZ1q8Rm--4f9JjWPONPNwrnQ22kxE7hVkrJ0D8PyJl9SNvuaVtM225pW4WP3j5Kr90E4fnJU7YIyB0oeDUPkP94_0f2N5zDtY4</recordid><startdate>20240906</startdate><enddate>20240906</enddate><creator>Zhou, Tuoyu</creator><creator>Wu, Jingyuan</creator><creator>Khan, Aman</creator><creator>Hu, Tianxiang</creator><creator>Wang, Yiqing</creator><creator>Salama, El-Sayed</creator><creator>Su, Shaochen</creator><creator>Han, Huawen</creator><creator>Jin, Weilin</creator><creator>Li, Xiangkai</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>HCIFZ</scope><scope>M0K</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2931-7565</orcidid></search><sort><creationdate>20240906</creationdate><title>A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome</title><author>Zhou, Tuoyu ; Wu, Jingyuan ; Khan, Aman ; Hu, Tianxiang ; Wang, Yiqing ; Salama, El-Sayed ; Su, Shaochen ; Han, Huawen ; Jin, Weilin ; Li, Xiangkai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-d5e61b2b367c1c79de381fda13888bf775f1946cdac1d13fb7dcd8f37821b3973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/326/2565/2134</topic><topic>631/326/41/2533</topic><topic>631/67/1504</topic><topic>Acids</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Ascorbic acid</topic><topic>Bile acids</topic><topic>Cancer therapies</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chemistry/Food Science</topic><topic>Colitis</topic><topic>Colon</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Digestive system</topic><topic>Fermented food</topic><topic>Food</topic><topic>Food Microbiology</topic><topic>Food Science</topic><topic>Gastrointestinal tract</topic><topic>Indoles</topic><topic>Inflammatory bowel disease</topic><topic>Intestinal microflora</topic><topic>Limosilactobacillus fermentum</topic><topic>Metabolites</topic><topic>Metagenomics</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Nutrition</topic><topic>Oxidative stress</topic><topic>Probiotics</topic><topic>Radiation therapy</topic><topic>Strain analysis</topic><topic>Surgery</topic><topic>Traditional foods</topic><topic>Tumorigenesis</topic><topic>Vitamin C</topic><topic>Weight loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Tuoyu</creatorcontrib><creatorcontrib>Wu, Jingyuan</creatorcontrib><creatorcontrib>Khan, Aman</creatorcontrib><creatorcontrib>Hu, Tianxiang</creatorcontrib><creatorcontrib>Wang, Yiqing</creatorcontrib><creatorcontrib>Salama, El-Sayed</creatorcontrib><creatorcontrib>Su, Shaochen</creatorcontrib><creatorcontrib>Han, Huawen</creatorcontrib><creatorcontrib>Jin, Weilin</creatorcontrib><creatorcontrib>Li, Xiangkai</creatorcontrib><collection>SpringerOpen</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Agricultural Science Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>SciTech Premium Collection</collection><collection>Agriculture Science Database</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 China</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>NPJ science of food</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Tuoyu</au><au>Wu, Jingyuan</au><au>Khan, Aman</au><au>Hu, Tianxiang</au><au>Wang, Yiqing</au><au>Salama, El-Sayed</au><au>Su, Shaochen</au><au>Han, Huawen</au><au>Jin, Weilin</au><au>Li, Xiangkai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome</atitle><jtitle>NPJ science of food</jtitle><stitle>npj Sci Food</stitle><addtitle>NPJ Sci Food</addtitle><date>2024-09-06</date><risdate>2024</risdate><volume>8</volume><issue>1</issue><spage>61</spage><epage>16</epage><pages>61-16</pages><artnum>61</artnum><issn>2396-8370</issn><eissn>2396-8370</eissn><abstract>Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic
Limosilactobacillus fermentum
GR-3, derived from traditional food “Jiangshui”, exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer
Lachnospiraceae
NK4A136 group and suppressing pro-inflammatory strain
Bacteroides
. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (
xseA
,
ALDH
) and butyrate synthesis gene (
bcd
), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39242568</pmid><doi>10.1038/s41538-024-00307-5</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-2931-7565</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2396-8370 |
| ispartof | NPJ science of food, 2024-09, Vol.8 (1), p.61-16, Article 61 |
| issn | 2396-8370 2396-8370 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_6ea069d85824446c8c1535d381052e44 |
| source | Publicly Available Content Database; PubMed Central; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/326/2565/2134 631/326/41/2533 631/67/1504 Acids Antioxidants Apoptosis Ascorbic acid Bile acids Cancer therapies Chemistry Chemistry and Materials Science Chemistry/Food Science Colitis Colon Colorectal cancer Colorectal carcinoma Digestive system Fermented food Food Food Microbiology Food Science Gastrointestinal tract Indoles Inflammatory bowel disease Intestinal microflora Limosilactobacillus fermentum Metabolites Metagenomics Microbiomes Microbiota Nutrition Oxidative stress Probiotics Radiation therapy Strain analysis Surgery Traditional foods Tumorigenesis Vitamin C Weight loss |
| title | A probiotic Limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via modulating gut microbiome |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T16%3A59%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20probiotic%20Limosilactobacillus%20fermentum%20GR-3%20mitigates%20colitis-associated%20tumorigenesis%20in%20mice%20via%20modulating%20gut%20microbiome&rft.jtitle=NPJ%20science%20of%20food&rft.au=Zhou,%20Tuoyu&rft.date=2024-09-06&rft.volume=8&rft.issue=1&rft.spage=61&rft.epage=16&rft.pages=61-16&rft.artnum=61&rft.issn=2396-8370&rft.eissn=2396-8370&rft_id=info:doi/10.1038/s41538-024-00307-5&rft_dat=%3Cproquest_doaj_%3E3101378153%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c366t-d5e61b2b367c1c79de381fda13888bf775f1946cdac1d13fb7dcd8f37821b3973%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3101378153&rft_id=info:pmid/39242568&rfr_iscdi=true |