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This investigation presents a multifunctional inulin complex (PB\/NKase@Inulin gel) incorporating Prussian blue nanozymes (PB NZs) and the thrombolytic agent nattokinase (NKase) for the therapeutic management of dextran sulfate sodium (DSS)\u2010induced UC and its associated intestinal and extraintestinal complications. Following oral administration, the PB\/NKase@Inulin gel, characterized by prolonged retention of PB NZs and NKase at inflamed colonic sites, can facilitate continuously ROS scavenging, attenuate oxidative stress damage, effectively reduce pro\u2010inflammatory cytokine levels. Importantly, PB\/NKase@Inulin gel can not only robustly inhibit inflammatory microthrombosis formation but also effectively lyses thrombi due to the potent thrombolytic properties of NKase both in vitro and in vivo. Furthermore, the PB\/NKase@Inulin gel is able to modulate gut microbiota homeostasis and alleviate multiple stresses responses (including anxiety and depression) in a UC mouse model via microbiota\u2010gut\u2010brain (MGB) axis interactions. Overall, the PB\/NKase@Inulin gel offers an innovative paradigm for comprehensive therapeutic interventions in DSS\u2010induced UC and its multifaceted complications.<\/jats:p>","DOI":"10.1002\/smll.202500726","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T01:14:00Z","timestamp":1745370840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comprehensive Management of Ulcerative Colitis and its Associated Intra\u2010Extra Intestinal Complications with a Multifunctional Inulin Hydrogel Complex"],"prefix":"10.1002","volume":"21","author":[{"given":"Silong","family":"Wu","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoyu","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering Hefei University of Technology  Hefei 230009 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenchao","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei 230031 China"},{"name":"Department of Radiation Oncology Anhui Provincial Cancer Hospital  Hefei 230031 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haisheng","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2883-5207","authenticated-orcid":false,"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei 230032 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"648","volume":"319","author":"Friedrich M. 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