{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:52:35Z","timestamp":1789678355244,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12432015,82560549"],"award-info":[{"award-number":["12432015,82560549"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2023GXLH\u2010033"],"award-info":[{"award-number":["2023GXLH\u2010033"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]}],"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                    Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is shaped by metabolic injury and tissue mechanics. This study investigated whether liver stiffening occurs early in MASLD and how extracellular matrix (ECM) mechanics interact with lipid droplet (LD) overload to promote inflammation, fibrogenesis, and lipid dysmetabolism. Clinical data, mouse models, and in vitro experiments are integrated. Liver stiffness shifted modestly with steatosis but increased substantially in the presence of inflammation. In a diet\u2010induced mouse model, liver stiffness increased before overt fibrosis. In cultured hepatocytes, stiff matrices combined with free fatty acid (FFA) induced steatosis synergistically amplified pro\u2010inflammatory and pro\u2010fibrotic signals, accompanied by cytoskeletal remodeling and nuclear deformation. YAP acted as a central mechanosensitive amplifier: stiffness drove YAP nuclear localization, and\n                    <jats:italic>YAP<\/jats:italic>\n                    knockdown blunted cytokine induction and fibrogenic gene expression under stiff + FFA conditions. Stiffness and LD overload jointly promoted lipogenesis and impaired lipophagy via YAP. Piezo1 is upregulated by stiff + FFA; its inhibition reduced Ca\n                    <jats:sup>2<\/jats:sup>\n                    \u207a influx and prevented YAP activation. Collectively, early liver stiffening, together with LD\u2010derived intracellular stress, engages a Piezo1\u2013YAP axis that amplifies inflammation, fibrogenesis, and disordered lipid metabolism, consistent with a proposed feed\u2010forward loop mechanism accelerating MASLD progression.\n                  <\/jats:p>","DOI":"10.1002\/advs.202519109","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:16:39Z","timestamp":1767590199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1\u2013YAP Mechanotransduction"],"prefix":"10.1002","volume":"13","author":[{"given":"Juan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi P. R. China"},{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi P. R. China"},{"name":"Bioinspired Engineering and Biomechanics Center (BEBC) Xi'an Jiaotong University Xi'an Shaanxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi P. R. China"},{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi P. R. China"},{"name":"Bioinspired Engineering and Biomechanics Center (BEBC) Xi'an Jiaotong University Xi'an Shaanxi P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanics and Control for Aerospace Structures Nanjing University of Aeronautics and Astronautics  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi P. R. China"},{"name":"Bioinspired Engineering and Biomechanics Center (BEBC) Xi'an Jiaotong University Xi'an Shaanxi P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Alazawi","sequence":"additional","affiliation":[{"name":"Barts Liver Centre Blizard Institute Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University  Haikou P. R. 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