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To overcome the insufficient catalytic activity of conventional cerium-based nanozymes, we designed an ultrasound-activated Bi@BTC heterojunction nanozyme. The ultrasound-activated carriers generated by bismuth core undergo effective electron-hole separation in the Janus Bi@BTC heterojunction. The holes are enriched in the valence band of the BTC shell, catalyzing the oxidation reaction of Ce3+. Benefiting from the proton-coupled electron transfer (PCET) effect of tannic acid and the electronic coupling at the heterointerface, Bi@BTC accelerates the Ce3+\/Ce4+ redox cycling, enabling a highly efficient and stable superoxide dismutase (SOD)\u2212catalase (CAT)-like catalytic cycle and thus robust elimination of multiple ROS in the IBD microenvironment. Density functional theory (DFT) calculations elucidate the catalytic pathways and cyclic mechanisms underlying the dual enzyme-mimetic activities, revealing key intermediates, transition states, and corresponding energy profiles. In vitro and in vivo assays confirmed that Bi@BTC alleviates intestinal inflammation by eliminating excess ROS, upregulating tight-junction proteins, promoting mucosal barrier repair, and restoring gut microbiota homeostasis. This work presents a boosted ROS-elimination strategy via ultrasound-activated heterojunction-mediated effect and PCET-driven cerium redox cycling, establishing a multifunctional paradigm that integrates ROS scavenging, anti-inflammation, mucosal repair, and gut microecological regulation.<\/jats:p>","DOI":"10.1021\/acsami.6c07000","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:02:06Z","timestamp":1787076126000},"page":"45987-46006","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound-Activated Janus Heterojunction-Mediated Enhanced Cascade Nanozyme for Inflammatory Bowel Disease Therapy"],"prefix":"10.1021","volume":"18","author":[{"given":"Siyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Tianjin University , , No. 92, Weijin Road, Nankai District , ,","place":["Tianjin, China, 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