{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:40:37Z","timestamp":1789155637439,"version":"build-2803163510"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"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><jats:title>Introduction<\/jats:title><jats:p>Ulcerative colitis (UC), a form of inflammatory irritable bowel disease, is characterized by a recurrent and persistent nonspecific inflammatory response. Polydatin (PD), a natural stilbenoid polyphenol with potent properties, exhibits unexpected beneficial effects beyond its well-documented anti-inflammatory and antioxidant activities. In this study, we presented evidence that PD confers protection against dextran sodium sulfate (DSS)-induced ulcerative colitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The protective effect of PD on colitis was examined in cultured caco-2 cells and DSS-induced colitis mouse model. Bulk RNA sequencing and differential gene expression analysis were used to investigate the protective mechanism of PD on DSS-induced colitis. Ferroptosis was determined by MDA levels, SOD levels, mitochondrial iron accumulation and ROS production. Ferroptosis-related proteins Slc7a11, Nrf2 and Gpx4 levels were measured by western blot, immunohistochemical and immunofluorescence staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD mitigated the DSS-induced increases in pro-inflammatory cytokines (IL-6, TNF-\u03b1, and IL-1\u03b2), alleviated colon length shortening, reduced morphological damage to the intestinal mucosa, and preserved tight junction proteins (TJ) occludin and Zonula occludens-1 (ZO-1) in both caco-2 cells and murine models of colitis. Mechanistically, PD reversed the reduction of Nrf2, Slc7a11 and Gpx4, the degree of nuclear translocation of Nrf2 induced by DSS <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> significantly. Moreover, the protective effect of PD is attenuated by erastin and resembled that of Fer-1 in caco-2 cells model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our study suggested that PD protects against DSS-induced ulcerative colitis via Nrf2\/Slc7a11\/Gpx4-dependent inhibition of ferroptosis signalling activation. Further investigation into the precise mechanisms underlying this phenomenon is warranted. The findings presented herein indicated that PD may serve as a potential therapeutic agent for patients with UC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1513020","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:10:50Z","timestamp":1736835050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Polydatin protects against DSS-induced ulcerative colitis via Nrf2\/Slc7a11\/Gpx4-dependent inhibition of ferroptosis signalling activation"],"prefix":"10.3389","volume":"15","author":[{"given":"Shimin","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialuo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/s0166-4328(01)00297-2","article-title":"Controlling the false discovery rate in behavior genetics research","volume":"125","author":"Benjamini","year":"2001","journal-title":"Behav. Brain Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1007\/s10571-020-00923-1","article-title":"SIRT1 activation by polydatin alleviates oxidative damage and elevates mitochondrial biogenesis in experimental diabetic neuropathy","volume":"41","author":"Bheereddy","year":"2021","journal-title":"Cell Mol. Neurobiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/0471142735.im1525s104","article-title":"Dextran sulfate sodium (DSS)-induced colitis in mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr. Protoc. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s11418-018-1241-7","article-title":"Polydatin protects against acute myocardial infarction-induced cardiac damage by activation of Nrf2\/HO-1 signaling","volume":"73","author":"Chen","year":"2019","journal-title":"J. Nat. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1002\/iid3.455","article-title":"Polydatin has anti-inflammatory and antioxidant effects in LPS-induced macrophages and improves DSS-induced mice colitis","volume":"9","author":"Chen","year":"2021","journal-title":"Immun. Inflamm. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/s41419-023-05716-0","article-title":"The interaction between ferroptosis and inflammatory signaling pathways","volume":"14","author":"Chen","year":"2023","journal-title":"Cell Death Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.imlet.2020.06.005","article-title":"Ferroptosis mediated DSS-induced ulcerative colitis associated with Nrf2\/HO-1 signaling pathway","volume":"225","author":"Chen","year":"2020","journal-title":"Immunol. Lett."},{"key":"B10","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1111\/apt.13958","article-title":"Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome","volume":"45","author":"Cremon","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1111\/jcmm.13342","article-title":"Metformin protects against intestinal barrier dysfunction via AMPK\u03b11-dependent inhibition of JNK signalling activation","volume":"22","author":"Deng","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00011-022-01672-1","article-title":"Molecular mechanisms of ferroptosis and relevance to inflammation","volume":"72","author":"Deng","year":"2023","journal-title":"Inflamm. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1046\/j.1365-2249.1998.00728.x","article-title":"Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines","volume":"114","author":"Dieleman","year":"1998","journal-title":"Clin. Exp. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"112397","DOI":"10.1016\/j.nut.2024.112397","article-title":"Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: a multicentric randomized controlled trial","volume":"122","author":"Di Nardo","year":"2024","journal-title":"Nutrition"},{"key":"B15","doi-asserted-by":"publisher","first-page":"101107","DOI":"10.1016\/j.redox.2019.101107","article-title":"NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis","volume":"23","author":"Dodson","year":"2019","journal-title":"Redox Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/s1535-6108(03)00050-3","article-title":"Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells","volume":"3","author":"Dolma","year":"2003","journal-title":"Cancer Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"113711","DOI":"10.1016\/j.biopha.2022.113711","article-title":"Ferroptosis interaction with inflammatory microenvironments: mechanism, biology, and treatment","volume":"155","author":"Dou","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"121766","DOI":"10.1016\/j.lfs.2023.121766","article-title":"Polydatin ameliorates inflammation and oxidative stress associated with MSU-induced gouty arthritis in mice by regulating PPAR-\u03b3 and ferritin activation","volume":"326","author":"Du","year":"2023","journal-title":"Life Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.3109\/13880209.2013.792849","article-title":"Polydatin: a review of pharmacology and pharmacokinetics","volume":"51","author":"Du","year":"2013","journal-title":"Pharm. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41420-022-01297-7","article-title":"Recent progress in ferroptosis: inducers and inhibitors","volume":"8","author":"Du","year":"2022","journal-title":"Cell Death Discov."},{"key":"B21","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1159\/000516191","article-title":"Renovation of intestinal barrier by polydatin in experimentally induced ulcerative colitis: comparative ultrastructural study with L-carnosine","volume":"210","author":"Ebrahim","year":"2021","journal-title":"Cells Tissues Organs"},{"key":"B22","doi-asserted-by":"publisher","first-page":"9529","DOI":"10.1007\/s00432-023-04762-7","article-title":"Polydatin radiosensitizes lung cancer while preventing radiation injuries by modulating tumor-infiltrating B cells","volume":"149","author":"Guo","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.bbrc.2021.03.108","article-title":"Polydatin alleviates traumatic brain injury: role of inhibiting ferroptosis","volume":"556","author":"Huang","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/aps.2016.123","article-title":"Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via inhibiting TLR2-mediated activation of the p38 MAPK\/NF-\u03baB pathway","volume":"38","author":"Jiang","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1016\/j.celrep.2019.01.043","article-title":"A genome-wide haploid genetic screen identifies regulators of glutathione abundance and ferroptosis sensitivity","volume":"26","author":"Jy","year":"2019","journal-title":"Cell Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"6474","DOI":"10.3390\/molecules27196474","article-title":"Polydatin: pharmacological mechanisms, therapeutic targets, biological activities, and Health benefits","volume":"27","author":"Karami","year":"2022","journal-title":"Molecules"},{"key":"B27","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"B28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3390\/pharmaceutics14010051","article-title":"Polydatin alleviates diabetes-induced hyposalivation through anti-glycation activity in db\/db mouse","volume":"14","author":"Kim","year":"2021","journal-title":"Pharmaceutics"},{"key":"B29","first-page":"103","article-title":"Caco-2 cell line","volume-title":"The impact of food bioactives on Health","author":"Lea","year":"2015"},{"key":"B30","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"166788","DOI":"10.1016\/j.bbadis.2023.166788","article-title":"Targeting Nrf2 for ferroptosis-based therapy: implications for overcoming ferroptosis evasion and therapy resistance in cancer","volume":"1869","author":"Lee","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1093\/bioinformatics\/btt087","article-title":"EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments","volume":"29","author":"Leng","year":"2013","journal-title":"Bioinformatics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12094-021-02669-8","article-title":"Ferroptosis: an iron-dependent cell death form linking metabolism, diseases, immune cell and targeted therapy","volume":"24","author":"Li","year":"2022","journal-title":"Clin. Transl. Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"9035547","DOI":"10.1155\/2022\/9035547","article-title":"Polydatin attenuates cisplatin-induced acute kidney injury via SIRT6-mediated autophagy activation","volume":"2022","author":"Li","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"116722","DOI":"10.1016\/j.biopha.2024.116722","article-title":"Ferroptosis in ulcerative colitis: potential mechanisms and promising therapeutic targets","volume":"175","author":"Long","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"B36","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.intimp.2018.09.009","article-title":"Polydatin ameliorates dextran sulfate sodium-induced colitis by decreasing oxidative stress and apoptosis partially via Sonic hedgehog signaling pathway","volume":"64","author":"Lv","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1016\/j.ejmech.2010.02.016","article-title":"Quantitative structure-antioxidant activity relationship of trans-resveratrol oligomers, trans-4,4\u2019-dihydroxystilbene dimer, trans-resveratrol-3-O-glucuronide, glucosides: trans-piceid, cis-piceid, trans-astringin and trans-resveratrol-4\u2019-O-beta-D-glucopyranoside","volume":"45","author":"Mikulski","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"929","DOI":"10.3390\/nu13030929","article-title":"Polydatin prevents calcium pyrophosphate crystal-induced arthritis in mice","volume":"13","author":"Oliviero","year":"2021","journal-title":"Nutrients"},{"key":"B39","doi-asserted-by":"publisher","first-page":"11455","DOI":"10.1074\/jbc.274.17.11455","article-title":"Cloning and expression of a plasma membrane cystine\/glutamate exchange transporter composed of two distinct proteins","volume":"274","author":"Sato","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.freeradbiomed.2018.09.014","article-title":"Role of GPX4 in ferroptosis and its pharmacological implication","volume":"133","author":"Seibt","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1016\/j.cell.2022.06.003","article-title":"Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications","volume":"185","author":"Stockwell","year":"2022","journal-title":"Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/s41392-023-01606-1","article-title":"Targeting ferroptosis opens new avenues for the development of novel therapeutics","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1038\/nprot.2017.044","article-title":"Chemically induced mouse models of acute and chronic intestinal inflammation","volume":"12","author":"Stefan","year":"2017","journal-title":"Nat. Protoc."},{"key":"B44","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1146\/annurev-pharmtox-052220-104025","article-title":"Targeting NRF2 and its downstream processes: opportunities and challenges","volume":"62","author":"Torrente","year":"2022","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2020.02.027","article-title":"Lipid peroxidation and ferroptosis: the role of GSH and GPx4","volume":"152","author":"Ursini","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1186\/1756-0500-6-360","article-title":"Dextran sodium sulfate inhibits the activities of both polymerase and reverse transcriptase: lithium chloride purification, a rapid and efficient technique to purify RNA","volume":"6","author":"Viennois","year":"2013","journal-title":"BMC Res. Notes"},{"key":"B47","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1021\/acschemneuro.2c00758","article-title":"Polydatin alleviates chronic stress-induced depressive and anxiety-like behaviors in a mouse model","volume":"14","author":"Wang","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2726","DOI":"10.3390\/cells11172726","article-title":"Molecular mechanisms of ferroptosis and relevance to cardiovascular disease","volume":"11","author":"Xie","year":"2022","journal-title":"Cells"},{"key":"B49","doi-asserted-by":"publisher","first-page":"105919","DOI":"10.1016\/j.intimp.2019.105919","article-title":"Inhibition of NET formation by polydatin protects against collagen-induced arthritis","volume":"77","author":"Yang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"3717","DOI":"10.1111\/jcmm.17937","article-title":"Polydatin alleviates bleomycin\u2010induced pulmonary fibrosis and alters the gut microbiota in a mouse model","volume":"27","author":"Yang","year":"2023","journal-title":"J. Cell Mol. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"B52","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","article-title":"Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells","volume":"15","author":"Yang","year":"2008","journal-title":"Chem. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41419-022-04775-z","article-title":"Interaction between macrophages and ferroptosis","volume":"13","author":"Yang","year":"2022","journal-title":"Cell Death Dis."},{"key":"B54","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1055\/s-0030-1250462","article-title":"Polydatin ameliorates DSS-induced colitis in mice through inhibition of nuclear factor-kappaB activation","volume":"77","author":"Yao","year":"2011","journal-title":"Planta Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"6687212","DOI":"10.1155\/2021\/6687212","article-title":"Polydatin attenuates OGD\/R-Induced neuronal injury and spinal cord ischemia\/reperfusion injury by protecting mitochondrial function via Nrf2\/ARE signaling pathway","volume":"2021","author":"Zhan","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B56","doi-asserted-by":"publisher","first-page":"116304","DOI":"10.1016\/j.jep.2023.116304","article-title":"Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome","volume":"309","author":"Zhang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"857879","DOI":"10.3389\/fnut.2022.857879","article-title":"Polydatin, A glycoside of resveratrol, is better than resveratrol in alleviating non-alcoholic fatty liver disease in mice fed a high-fructose diet","volume":"9","author":"Zhao","year":"2022","journal-title":"Front. Nutr."},{"key":"B58","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.redox.2018.07.002","article-title":"Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1\/Nrf2 pathway","volume":"18","author":"Zhao","year":"2018","journal-title":"Redox Biol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"9947191","DOI":"10.1155\/2022\/9947191","article-title":"Polydatin attenuates cisplatin-induced acute kidney injury by inhibiting ferroptosis","volume":"2022","author":"Zhou","year":"2022","journal-title":"Oxid. Med. Cell Longev."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1513020\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:10:56Z","timestamp":1736835056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1513020\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":59,"alternative-id":["10.3389\/fphar.2024.1513020"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1513020","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,14]]},"article-number":"1513020"}}