{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:06:04Z","timestamp":1790766364806,"version":"4.1.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The prevalence of diarrhoea-predominant irritable bowel syndrome (IBS-D) is high and significantly impairs patient quality of life. Berberine, a naturally occurring isoquinoline alkaloid, shows promise in combination with brain-gut axis-targeted drugs for relieving abdominal pain, bloating, and diarrhoea in IBS-D. However, current clinical evidence remains insufficient to conclusively substantiate its efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim of the study<\/jats:title>\n                    <jats:p>Through a systematic literature review and meta-analysis, this work comprehensively evaluated the efficacy and safety of berberine in combination with brain-gut axis-targeted medications for the treatment of IBS-D, thereby providing evidence to inform clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>On 1 December 2025, a comprehensive search was conducted across ten databases, including PubMed, Web of Science (WOS), the Cochrane Library, and Embase, to identify randomized controlled trials (RCTs) evaluating berberine in combination with brain-gut axis-targeted medications. Two reviewers independently screened the literature according to predefined inclusion and exclusion criteria, followed by data extraction. The risk of bias tool developed by the Cochrane Collaboration was used to assess the methodological quality of the included studies, and data were analyzed using RStudio software. When two or more studies had comparable interventions and outcome measures, a meta-analysis was conducted, otherwise, a qualitative synthesis was performed. The certainty of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 19 RCTs involving 1,489 participants were included in the analysis. Compared with the control groups, the intervention groups showed significant improvements in IBS-D symptoms and patient quality of life. Specifically, combination therapy incorporating berberine significantly increased the overall treatment response rate (odds ratio = 4.19, 95% confidence intervals (CI): 3.13\u20135.61). With respect to continuous outcomes, combination therapy significantly reduced overall symptom scores (standardized mean difference (SMD) = \u22123.47, 95% CI: \u22126.65 to \u22120.29), particularly reflected by reductions in abdominal pain and bloating severity, along with improvements in diarrhoea-related symptoms. Furthermore, no serious adverse events were reported across the included trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Berberine combined with brain-gut axis-targeted medications shows promising efficacy and acceptable safety in the treatment of IBS-D. However, existing studies are limited by small sample sizes and methodological weaknesses, and the overall strength of evidence remains insufficient. Larger, rigorously designed RCTs are needed to further confirm its efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251238184<\/jats:ext-link>\n                      , identifier CRD420251238184.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1795170","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:41:26Z","timestamp":1790764886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A meta-analysis of berberine combined with brain-gut axis-targeted agents for diarrhoea-predominant irritable bowel syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Nanxi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Spleen and Stomach Diseases, Xi\u2019an Hospital of Traditional Chinese Medicine","place":["Xi\u2019an, China"]},{"name":"The First School of Clinical Medicine, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach Diseases, Xi\u2019an Hospital of Traditional Chinese Medicine","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixia","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach Diseases, Xi\u2019an Hospital of Traditional Chinese Medicine","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach Diseases, Xi\u2019an Hospital of Traditional Chinese Medicine","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxu","family":"Liu","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41575-020-0286-8","article-title":"Global burden of irritable bowel syndrome: trends, predictions and risk factors","volume":"17","author":"Black","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B2","first-page":"39","article-title":"The effect of bifidobacterium tetravaccine tabl combined berberine in treatment of diarrhea-predominat irritable bowelsyndrome. China pract","volume":"4","author":"Chen","year":"2009","journal-title":"Med"},{"key":"B3","first-page":"7","article-title":"Clinical observation of berberine combined with birid triple viable in the treatment of diarrhea predominant irritable bowel syndrome","volume":"2008","author":"Chen","year":"2008","journal-title":"Pract. Clin. J. Integr. Tradit. Chin. West. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1142\/S0192415X14500669","article-title":"Effects of berberine in the gastrointestinal tract - a review of actions and therapeutic implications","volume":"42","author":"Chen","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1002\/ptr.5475","article-title":"A randomized clinical trial of berberine hydrochloride in patients with diarrhea-predominant irritable bowel syndrome","volume":"29","author":"Chen","year":"2015","journal-title":"Phytotherapy Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"817100","DOI":"10.3389\/fendo.2022.817100","article-title":"Neurotransmitter and intestinal interactions: focus on the microbiota-gut-brain axis in irritable bowel syndrome","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Endocrinol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.23736\/S1121-421X.19.02649-7","article-title":"Role of a berberine-based nutritional supplement in reducing diarrhea in subjects with functional gastrointestinal disorders","volume":"66","author":"Di Pierro","year":"2020","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"II1","DOI":"10.1136\/gut.45.2008.ii1","article-title":"The functional gastrointestinal disorders and the rome II process","volume":"45","author":"Drossman","year":"1999","journal-title":"Gut"},{"key":"B9","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/j.1443-9573.2006.00265.x","article-title":"Rome III: the new criteria","volume":"7","author":"Drossman","year":"2006","journal-title":"Chin. J. Dig. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"13573","DOI":"10.1111\/jcmm.16049","article-title":"Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation","volume":"24","author":"Ehteshamfar","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2049-9256-2-4","article-title":"The relationship between irritable bowel syndrome and psychiatric disorders: from molecular changes to clinical manifestations","volume":"2","author":"Fadgyas-Stanculete","year":"2014","journal-title":"J. Mol. Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1186\/1471-2458-13-832","article-title":"Patients with irritable bowel syndrome are more burdened by co-morbidity and worry about serious diseases than healthy controls-eight years follow-up of IBS patients in primary care","volume":"13","author":"Faresj\u00f6","year":"2013","journal-title":"BMC Public Health"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1056\/NEJMra1607547","article-title":"Irritable bowel syndrome","volume":"376","author":"Ford","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B14","first-page":"1826","article-title":"Clinical observation of berberine combined with flupentixol and melitracen tablets in the treatment of diarrhea-predominant irritable bowel syndrome","volume":"32","author":"Fu","year":"2010","journal-title":"Hebei J. Tradit. Chin. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1097\/CAD.0000000000000835","article-title":"Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78","volume":"31","author":"Gong","year":"2020","journal-title":"Anti-Cancer Drugs"},{"key":"B16","doi-asserted-by":"publisher","first-page":"S118","DOI":"10.1038\/533S118a","article-title":"Irritable bowel syndrome: 4 big questions","volume":"533","author":"Grayson","year":"2016","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"ITC113","DOI":"10.7326\/ANNALS-25-01965","article-title":"Irritable bowel syndrome","volume":"178","author":"Greer","year":"2025","journal-title":"Ann. Intern. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00210-025-04376-5","article-title":"Berberine mitigates colitis-associated neuroinflammation and anxiety through modulation of the AMPK\/NURR1 pathway","volume":"2025","author":"Habiba","year":"2025","journal-title":"Schmiedeb. Arch. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"10161","DOI":"10.3390\/ijms262010161","article-title":"Berberine alleviates intestinal inflammation by disrupting pathological macrophage\u2013epithelial crosstalk in macrophage\u2013organoid co-culture model","volume":"26","author":"Han","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B20","first-page":"151","article-title":"Clinical efficacy of combination treatment of trimebutine and berberine to irritable bowel syndrome","volume":"18","author":"He","year":"2009","journal-title":"Chin. J. Ethnomed. Ethnopharm."},{"key":"B21","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"B22","first-page":"3031","article-title":"Clinical observation on compound berberine in treatment of irritable bowel syndrome","volume":"2008","author":"Hua","year":"2008","journal-title":"Med. Recapitul."},{"key":"B23","first-page":"226","article-title":"Clinical observation of berberine combined with smecta in the treatment of diarrhea-predominant irritable bowel syndrome","volume":"2006","author":"Ji","year":"2006","journal-title":"J. Handan Med. Coll."},{"key":"B24","first-page":"15","article-title":"Clinical observation of berberine combined with Bifidobacterium tetravaccine tablets in the treatment of diarrhea-predominant irritable bowel syndrome","volume":"20","author":"Ji","year":"2020","journal-title":"Pract. Clin. J. Integr. Tradit. Chin. West. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1089\/jmf.2014.3346","article-title":"Berberine ameliorates allodynia induced by chronic constriction injury of the sciatic nerve in rats","volume":"18","author":"Kim","year":"2015","journal-title":"J. Med. Food"},{"key":"B26","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1089\/jmf.2012.2648","article-title":"Berberine ameliorates cold and mechanical allodynia in a rat model of diabetic neuropathy","volume":"16","author":"Kim","year":"2013","journal-title":"J. Med. Food"},{"key":"B27","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3892\/mmr.2019.10823","article-title":"Berberine ameliorates lipopolysaccharide-induced inflammatory responses in mouse inner medullary collecting duct-3 cells by downregulation of NF-\u03baB pathway","volume":"21","author":"Kim","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3390\/microorganisms5040066","article-title":"The gut microbiome feelings of the brain: a perspective for non-microbiologists","volume":"5","author":"Lerner","year":"2017","journal-title":"Microorganisms"},{"key":"B29","first-page":"273","article-title":"Clinical observation of berberine tablets combined with compound Lactobacillus acidophilus tablets in treatment of diarrhea-predominant irritable bowel syndrome","volume":"18","author":"Liang","year":"2016","journal-title":"Zhejiang Clin. Med. J."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e70033","DOI":"10.1111\/nmo.70033","article-title":"Berberine improves depression-like behaviors and gastrointestinal dysfunction in 6-hydroxydopamine-induced parkinson's disease rats","volume":"37","author":"Liu","year":"2025","journal-title":"Neurogastroenterol. Motil."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1053\/j.gastro.2014.02.037","article-title":"Brain-gut microbiome interactions and functional bowel disorders","volume":"146","author":"Mayer","year":"2014","journal-title":"Gastroenterology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","article-title":"Bowel disorders","volume":"150","author":"Mearin","year":"2016","journal-title":"Gastroenterology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrgastro.2012.162","article-title":"Agents that act luminally to treat diarrhoea and constipation","volume":"9","author":"Menees","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"B35","first-page":"1339","article-title":"Clinical observation of paroxetine combined with berberine hydrochloride in the treatment of 45 cases of diarrhea type irritable bowel syndrome","volume":"2005","author":"Ou","year":"2005","journal-title":"J. Clin. Res."},{"key":"B36","first-page":"30","article-title":"Clinical observation of jiawei tongxie yaofang combined with berberine in the treatment of diarrhea-predominant irritable bowel syndrome","volume":"16","author":"Peng","year":"2010","journal-title":"Guid. J. Tradit. Chin. Med. Pharm."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/jcm7010006","article-title":"The gut-brain axis and the microbiome: clues to pathophysiology and opportunities for novel management strategies in irritable bowel syndrome (IBS)","volume":"7","author":"Quigley","year":"2018","journal-title":"J. Clin. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/phar.1712","article-title":"Update on the management of diarrhea-predominant irritable bowel syndrome: focus on rifaximin and eluxadoline","volume":"36","author":"Rivkin","year":"2016","journal-title":"Pharmacotherapy"},{"key":"B39","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3390\/foods8100522","article-title":"Berberis plants-drifting from farm to food applications, phytotherapy, and phytopharmacology","volume":"8","author":"Salehi","year":"2019","journal-title":"Foods"},{"key":"B40","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nrgastro.2016.110","article-title":"Diagnosis: rome IV criteria for FGIDs - an improvement or more of the same?","volume":"13","author":"Sood","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1186\/s13287-025-04448-6","article-title":"Mesenchymal stem cell-derived apoptotic vesicles regulate irritable bowel syndrome in mice via the 5-HT brain-gut axis","volume":"16","author":"Sun","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"B42","doi-asserted-by":"publisher","first-page":"11934","DOI":"10.1038\/s41598-019-48331-w","article-title":"Berberine improved experimental chronic colitis by regulating interferon-\u03b3-and IL-17A-producing Lamina propria CD4+ T cells through AMPK activation","volume":"9","author":"Takahara","year":"2019","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1053\/j.gastro.2010.07.053","article-title":"Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome","volume":"140","author":"Tillisch","year":"2011","journal-title":"Gastroenterology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/j.biopha.2018.04.161","article-title":"Berberine suppresses growth and metastasis of endometrial cancer cells via miR-101\/COX-2","volume":"103","author":"Wang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B45","doi-asserted-by":"publisher","first-page":"155258","DOI":"10.1016\/j.phymed.2023.155258","article-title":"Inhibition of inflammation by berberine: molecular mechanism and network pharmacology analysis","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"155163","DOI":"10.1016\/j.phymed.2023.155163","article-title":"Baizhu shaoyao decoction restores the intestinal barrier and brain\u2013gut axis balance to alleviate diarrhea-predominant irritable bowel syndrome via FoxO1\/FoxO3a","volume":"122","author":"Wei","year":"2024","journal-title":"Phytomedicine"},{"key":"B47","first-page":"124","article-title":"Clinical observation on 30 cases of diarrhea-predominant irritable bowel syndrome treated with modified shenling baizhu powder and berberine","volume":"2006","author":"Wu","year":"2006","journal-title":"Chin. J. Tradit. Med. Sci. Technol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"7748351","DOI":"10.1155\/2025\/7748351","article-title":"Based on proteomics data revealing the potential of traditional Chinese medicine in treating irritable bowel syndrome","volume":"2025","author":"Wu","year":"2025","journal-title":"Mediat. Inflamm."},{"key":"B49","first-page":"1666","article-title":"Clinical observation of berberine combined with Bacillus subtilis and Enterococcus faecium enteric-coated capsules in the treatment of diarrhea-predominant irritable bowel syndrome","volume":"32","author":"Yin","year":"2010","journal-title":"Hebei J. Tradit. Chin. Med."},{"key":"B50","first-page":"427","article-title":"Efficacy observation of berberine combined with compound glutamine in the treatment of 36 cases of diarrhea-predominant irritable bowel syndrome","volume":"30","author":"Yu","year":"2012","journal-title":"J. Guangdong Med. Univ."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1756284820961299","DOI":"10.1177\/1756284820961299","article-title":"Berberine for diarrhea in children and adults: a systematic review and meta-analysis","volume":"13","author":"Yu","year":"2020","journal-title":"Ther. Adv. Gastroenterology"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2263209","DOI":"10.1080\/19490976.2023.2263209","article-title":"Low-level inflammation, immunity, and brain-gut axis in IBS: unraveling the complex relationships","volume":"15","author":"Yuan","year":"2023","journal-title":"Gut Microbes"},{"key":"B53","first-page":"63","article-title":"Berberine hydrochloride combined with compound lactic acid bacteria in the treatment of irritable bowel syndrome","volume":"2004","author":"Zeng","year":"2004","journal-title":"Chin. Prev. Med. J."},{"key":"B54","first-page":"72","article-title":"Observation on the curative effect of tongxie yaofang combined with berberine in the treatment of diarrhea-predominant irritable bowel syndrome","volume":"5","author":"Zeng","year":"2012","journal-title":"Chin. J. Clin. Ration. Drug Use"},{"key":"B55","first-page":"126","article-title":"Since the proposed tonifying spleen yiqi decoction combined berberine hydrochloride treatment of diarrhea type irritable bowel syndrome random parallel control study","volume":"27","author":"Zhao","year":"2013","journal-title":"J. Pract. Tradit. Chin. Intern. Med."},{"key":"B56","first-page":"10","article-title":"Clinical observation of berberine combined with bifidobacterium tetravaccine tablets in the treatment of diarrhea-type irritable bowel syndrome","volume":"22","author":"Zhao","year":"2008","journal-title":"Clin. Misdiagn. Misther."},{"key":"B57","first-page":"37","article-title":"Clinical observation on treating diarrhea-predominant irritable bowel syndrome with berberine plus pinaverium bromide","volume":"5","author":"Zhao","year":"2013","journal-title":"Clin. J. Chin. Med."},{"key":"B58","first-page":"92","article-title":"Berberine, bifidobiogen-livzon and deanxit combined treatment of irritable bowel syndrome. Zhejiang pract","volume":"2006","author":"Zhu","year":"2006","journal-title":"Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1795170\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:41:30Z","timestamp":1790764890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1795170\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":58,"alternative-id":["10.3389\/fphar.2026.1795170"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1795170","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1795170"}}