{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:37:30Z","timestamp":1792179450710,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Engineered bacteria offer a promising therapeutic platform but often display plasmid instability and antibiotic dependence. A synthetic dual\u2010key genetic circuit is established in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Nissle 1917 (EcN) by deleting both\n                    <jats:italic>asd<\/jats:italic>\n                    and\n                    <jats:italic>thyA<\/jats:italic>\n                    genes, generating an auxotrophic chassis that requires dual\u2010plasmid complementation for survival. The \u201clysis module\u201d restores\n                    <jats:italic>asd<\/jats:italic>\n                    function and incorporates a quorum\u2010sensing system for self\u2010regulated lysis and controlled protein release (\u201cOne Key\u201d). By contrast, the \u201cexpression module\u201d complements\n                    <jats:italic>thyA<\/jats:italic>\n                    and co\u2010delivers an interleukin\u20102 (IL\u20102) mutant and the membrane protein Amuc_1100 to modulate immune balance and repair the intestinal barrier (\u201cDual Keys\u201d). This dual\u2010key design enabled antibiotic\u2010free plasmid stability, precise population control, and sustained therapeutic protein secretion. Oral administration of the engineered strain significantly alleviated colitis in mice by enhancing regulatory T\u2010cell expansion, restoring epithelial integrity, and reshaping the gut microbiota. This modular system provides a safe, stable, and programmable strategy for live bacterial therapy against immune and mucosal diseases.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520434","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:12:01Z","timestamp":1770981121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual\u2010Key Genetic Circuit Enables Stable and Self\u2010Regulated Engineered Bacteria for the Treatment of Ulcerative Colitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Shuaijie","family":"Ding","sequence":"first","affiliation":[{"name":"Institute of Health and Medicine (IHM) Hefei Comprehensive National Science Center  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine (IHM) Hefei Comprehensive National 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Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9982-8972","authenticated-orcid":false,"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine (IHM) Hefei Comprehensive National Science Center  Hefei Anhui 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