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Adv."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>\n                    Chronic lung graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains difficult to treat, and broad immunosuppression increases infection risk. Single-cell profiling of bronchoalveolar lavage from bronchiolitis obliterans lesions revealed collapse of an epithelial nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) metabolic axis with pathogenic immune-epithelial remodeling, nominating NAD\n                    <jats:sup>+<\/jats:sup>\n                    restoration as an entry point. Because free NAD\n                    <jats:sup>+<\/jats:sup>\n                    is poorly cell-permeable and rapidly consumed, we engineered CaNAD\n                    <jats:sup>+<\/jats:sup>\n                    -PGB-LiP (CNAPL), a high-payload NAD\n                    <jats:sup>+<\/jats:sup>\n                    nanomedicine enabling direct intracellular replenishment. In murine allo-HSCT GVHD, CNAPL improved clinical scores and survival, reduced vascular and epithelial injury, and curtailed hyperinflammation and effector overactivation across GVHD target organs. Unlike immunosuppression, CNAPL preserved phagocytosis, NK\/NKT cell (natural killer\/natural killer T cell) cytotoxicity, and T cell memory. In posttransplant influenza or\n                    <jats:italic toggle=\"yes\">Klebsiella<\/jats:italic>\n                    infection, CNAPL maintained pathogen control without rekindling GVHD, decoupling inflammation control from infection susceptibility. This metabolism-centered, host-directed strategy restores immune-tissue homeostasis and provides a practical translational path for durable lung GVHD control with preserved antimicrobial defense.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef3338","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:58:42Z","timestamp":1792778322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["NAD\n                    <sup>+<\/sup>\n                    metabolic restoration resolves the inflammation-immunocompetence trade-off in lung graft-versus-host disease"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8170-0081","authenticated-orcid":true,"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake 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