{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:35:46Z","timestamp":1793205346117,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"60","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with limited therapeutic options, particularly those capable of selectively reinforcing intestinal epithelial barrier integrity while preserving immune homeostasis. Here, Rhoifolin (3, 10\u00a0mg\/kg) dose\u2010dependently alleviates DSS and TNBS\u2010induced colitis in mice. Mechanistically, Rhoifolin selectively potentiates ILC3s effector function without affecting their proliferation, apoptosis, intestinal homing, developmental differentiation, or the distribution of CCR6\n                    <jats:sup>+<\/jats:sup>\n                    , NKp46\n                    <jats:sup>+<\/jats:sup>\n                    , and double\u2010negative ILC3s subsets. This functional enhancement promotes IL\u201022 production, thereby reinforcing epithelial barrier integrity in colonic epithelial cells and organoids. Integrated transcriptomics and untargeted metabolomics identified nicotinamide salvage as a central metabolic program driving ILC3s functional enhancement. NMNAT1 was identified as a direct molecular target of Rhoifolin. Molecular docking and dynamic simulations pinpointed Leu155 as a critical residue mediating Rhoifolin\u2010NMNAT1 interaction, and mutation of Leu155 antagonized metabolic activation and IL\u201022 induction. Consistently, Rhoifolin\u2010induced NAD+ elevation enhanced SIRT1 activity, leading to FOXO1 deacetylation and nuclear translocation. Further CUT&amp;Tag\u2010qPCR demonstrated FOXO1 enrichment at\n                    <jats:italic>Il22<\/jats:italic>\n                    promoter, driving IL\u201022 transcription in ILC3s. Collectively, our findings identify Rhoifolin as a potent ILC3s effector function enhancer and uncover a previously unrecognized NMNAT1\u2010NAD+\u2010SIRT1\u2010FOXO1 axis linking immunometabolic and epigenetic regulation to intestinal barrier protection, highlighting ILC3s empowerment as a promising therapeutic strategy for UC.\n                  <\/jats:p>","DOI":"10.1002\/advs.76935","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:43:47Z","timestamp":1786103027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rhoifolin Alleviates Ulcerative Colitis by Targeting NMNAT1 and Activating SIRT1\u2010FOXO1 Signaling to Enhance ILC3s Effector Function"],"prefix":"10.1002","volume":"13","author":[{"given":"Hongqiong","family":"Yang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory For Functional Substance of Chinese Medicine School of Pharmacy Nanjing University of Chinese Medicine  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Functional Substance of Chinese Medicine School of Pharmacy Nanjing University of Chinese Medicine  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Feng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Functional Substance of Chinese Medicine School of Pharmacy Nanjing University of Chinese Medicine  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Ma","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Functional Substance of Chinese Medicine School of Pharmacy Nanjing University of Chinese Medicine  Nanjing People's Republic of 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