{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:53:18Z","timestamp":1776941598009,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2304400"],"award-info":[{"award-number":["2022YFC2304400"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2304401"],"award-info":[{"award-number":["2022YFC2304401"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2304404"],"award-info":[{"award-number":["2022YFC2304404"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900071"],"award-info":[{"award-number":["81900071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200034"],"award-info":[{"award-number":["82200034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JCYJ20240813115821029"],"award-info":[{"award-number":["JCYJ20240813115821029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010004"],"award-info":[{"award-number":["2021A1515010004"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20190809143601759"],"award-info":[{"award-number":["JCYJ20190809143601759"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Vascular Research Initiative"],"award-info":[{"award-number":["Vascular Research Initiative"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012449","name":"Southern University of Science and Technology","doi-asserted-by":"publisher","award":["Y01416133"],"award-info":[{"award-number":["Y01416133"]}],"id":[{"id":"10.13039\/501100012449","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                    Pulmonary infections and fibrosis remain difficult to treat because current interventions target isolated pathways rather than the coupled axes of inflammation, barrier integrity, and tissue remodeling. Here, it is shown that inhalationally delivered, lung\u2010targeted antisense oligonucleotides against angiopoietin\u2010like 4 (\n                    <jats:italic>Angptl4<\/jats:italic>\n                    \u2010ASO) attenuate both infectious and fibrotic lung disease. In murine models of bacterial and viral pneumonia,\n                    <jats:italic>Angptl4<\/jats:italic>\n                    \u2010ASO reduces inflammatory cell infiltration, preserves alveolar architecture, and improves host defence. In bleomycin\u2010induced fibrosis, treatment lowered Ashcroft scores, collagen deposition, and \u03b1\u2010smooth muscle actin (SMA) expression, indicating broad efficacy across acute and chronic injury. Comparative transcriptomics reveal model\u2010specific responses, immune and oxidative\u2010stress programs in pneumonia versus extracellular matrix (ECM)\u2010remodeling pathways in fibrosis, yet nearly half of all changes converge on a shared ANGPTL4\u2010regulated network linking hypoxic, inflammatory, apoptotic, and stress response programs. This conserved signature suggests that ANGPTL4 functions as a central regulator of injury resolution regardless of the initiating insult. Mechanistically,\n                    <jats:italic>Angptl4<\/jats:italic>\n                    \u2010ASO reinforced epithelial barrier integrity through coordinated regulation of tight junction and glycoprotein pathways. Longitudinal tracking of a Sulfo\u2010Cyanine 5 (Cy5)\u2010conjugated\n                    <jats:italic>Angptl4<\/jats:italic>\n                    \u2010ASO confirmed a lung\u2010retentive biodistribution, with sustained intrapulmonary localization and minimal systemic dissemination over a 144\u2010hour window. Collectively, these findings position inhaled ANGPTL4\u2010ASO as a host\u2010directed, multi\u2010axis therapeutic strategy that addresses shared and context\u2010specific drivers of diverse pulmonary pathologies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501909","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:46:31Z","timestamp":1774262791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhaled Angiopoietin\u2010Like 4 Antisense Oligonucleotide Therapy for Lung Injury and Fibrosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Haiyang","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Otolaryngology The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"},{"name":"Department of Thoracic Surgery The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyang","family":"Tan","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong\u2010Hong Kong Universities for Vascular Homeostasis and Diseases, Department of Pharmacology School of Medicine Southern University of Science and Technology Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoya","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shenzhen Children's Hospital  Shenzhen Guangdong Province 518026 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Qu","sequence":"additional","affiliation":[{"name":"Shenzhen Center for Disease Control and Prevention  Shenzhen 518055 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0007-1688","authenticated-orcid":false,"given":"Damien","family":"Chua","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore  11 Mandalay Road Singapore 308232 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-7872","authenticated-orcid":false,"given":"Hong Sheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore  11 Mandalay Road Singapore 308232 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph Han Sol","family":"Kim","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore  11 Mandalay Road Singapore 308232 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore  11 Mandalay Road Singapore 308232 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changfei","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pathology The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingzi","family":"Liu","sequence":"additional","affiliation":[{"name":"Intervention and Cell Therapy Center Peking University Shenzhen Hospital  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhi","family":"Li","sequence":"additional","affiliation":[{"name":"Intervention and Cell Therapy Center Peking University Shenzhen Hospital  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jikang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Intervention Peking University Shenzhen Hospital  Shenzhen Guangdong 518000 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengshi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingmin","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoumeh","family":"Motamedi Joibari","sequence":"additional","affiliation":[{"name":"Lipigon Pharmaceuticals AB  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan K","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Lipigon Pharmaceuticals AB  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguan Soon","family":"Tan","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore  11 Mandalay Road Singapore 308232 Singapore"},{"name":"School of Biological Sciences Nanyang Technological University Singapore  60 Nanyang Drive Singapore 637551 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunping","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-7837","authenticated-orcid":false,"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong\u2010Hong Kong Universities for Vascular Homeostasis and Diseases, Department of Pharmacology School of Medicine Southern University of Science and Technology Shenzhen P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03159-9"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu892"},{"key":"e_1_2_9_3_1","first-page":"30","author":"Mylvaganam R. J.","year":"2021","journal-title":"Eur. Respir. Rev."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106383"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1351122"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20210879"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2022.11.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.680178"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-013-0678-0"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.01.011"},{"key":"e_1_2_9_11_1","volume":"10","author":"Li L.","year":"2019","journal-title":"mBio"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0304OC"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20110102"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.05.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-023-01753-9"},{"key":"e_1_2_9_16_1","first-page":"0827","volume":"5","author":"Bhatraju P. K.","year":"2023","journal-title":"Crit. Care Explor."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001734"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4145"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.004"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24969"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-024-00326-5"},{"key":"e_1_2_9_24_1","first-page":"9","author":"Dhuri K.","year":"2020","journal-title":"J. Clin. Med."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303481"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11769-x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202309-840ED"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24479"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183330"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvx077"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512621200"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4907"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5149"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-328716"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.02.071"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202100863"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32834f44c7"},{"key":"e_1_2_9_40_1","volume-title":"C. National Clinical Guideline","author":"Copyright \u00a9 National Clinical Guideline Centre","year":"2014"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705835"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-256"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009925"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00883"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.021"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.01.020"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42111"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114451"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-69020-3"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000534151"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042025"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06806-3"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.02.027"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03313-2"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2017.01.006"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202205-0893OC"},{"key":"e_1_2_9_57_1","author":"Li L.","year":"2015","journal-title":"Cell Rep."},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.3c04925"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-021-01514-6"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106542"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-3-r22"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202501909","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202501909","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202501909","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:27:14Z","timestamp":1776940034000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202501909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":65,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202501909"],"URL":"https:\/\/doi.org\/10.1002\/advs.202501909","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"2025-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01909"}}