{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:47:38Z","timestamp":1793260058867,"version":"4.5.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1303900"],"award-info":[{"award-number":["2016YFC1303900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007185","name":"University of California, Los Angeles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Redox Biology"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.redox.2020.101638","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T01:46:45Z","timestamp":1594604805000},"page":"101638","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":242,"special_numbering":"C","title":["Targeting NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII\/ERK1\/2\/MLCK and endothelial cell barrier dysfunction"],"prefix":"10.1016","volume":"36","author":[{"given":"Jinyao","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe G.N.","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.redox.2020.101638_bib1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev-pathol-011110-130158","article-title":"The acute respiratory distress syndrome: pathogenesis and treatment","volume":"6","author":"Matthay","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.redox.2020.101638_bib2","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1001\/jama.2017.21907","article-title":"Acute respiratory distress syndrome: advances in diagnosis and treatment","volume":"319","author":"Fan","year":"2018","journal-title":"JAMA"},{"key":"10.1016\/j.redox.2020.101638_bib3","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of Care, and mortality for patients with acute respiratory distress syndrome in intensive Care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.redox.2020.101638_bib4","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1152\/jappl.2001.91.4.1487","article-title":"Cytoskeletal regulation of pulmonary vascular permeability","volume":"91","author":"Dudek","year":"2001","journal-title":"J. Appl. Physiol. (Bethesda, Md. 1985)"},{"key":"10.1016\/j.redox.2020.101638_bib5","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/jcb.20088","article-title":"Endothelial cell barrier regulation by sphingosine 1-phosphate","volume":"92","author":"McVerry","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.redox.2020.101638_bib6","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1056\/NEJM200005043421806","article-title":"The acute respiratory distress syndrome","volume":"342","author":"Ware","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.redox.2020.101638_bib7","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1152\/physrev.00012.2005","article-title":"Signaling mechanisms regulating endothelial permeability","volume":"86","author":"Mehta","year":"2006","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.redox.2020.101638_bib8","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1172\/JCI60331","article-title":"The acute respiratory distress syndrome","volume":"122","author":"Matthay","year":"2012","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.redox.2020.101638_bib9","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1089\/ars.2007.1940","article-title":"Roles of oxidants and redox signaling in the pathogenesis of acute respiratory distress syndrome","volume":"10","author":"Tasaka","year":"2008","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.redox.2020.101638_bib10","doi-asserted-by":"crossref","first-page":"314s","DOI":"10.1378\/chest.122.6_suppl.314S","article-title":"Oxidant-antioxidant balance in acute lung injury","volume":"122","author":"Lang","year":"2002","journal-title":"Chest"},{"key":"10.1016\/j.redox.2020.101638_bib11","doi-asserted-by":"crossref","DOI":"10.1183\/09031936.98.12061486","article-title":"Reactive oxygen species in acute lung injury","volume":"12","author":"Ruffmann","year":"1998","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.redox.2020.101638_bib12","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1089\/ars.2007.1785","article-title":"Role of oxidants in lung injury during sepsis","volume":"9","author":"Guo","year":"2007","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.redox.2020.101638_bib13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s001340050813","article-title":"Antioxidant status in patients with acute respiratory distress syndrome","volume":"25","author":"Metnitz","year":"1999","journal-title":"Intensive Care Med."},{"key":"10.1016\/j.redox.2020.101638_bib14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0165-6147(03)00233-5","article-title":"The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases","volume":"24","author":"Cai","year":"2003","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.redox.2020.101638_bib15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41569-019-0260-8","article-title":"NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets","volume":"17","author":"Zhang","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.redox.2020.101638_bib16","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1113\/EP086204","article-title":"NOX5: molecular biology and pathophysiology","volume":"104","author":"Touyz","year":"2019","journal-title":"Exp. Physiol."},{"key":"10.1016\/j.redox.2020.101638_bib17","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.freeradbiomed.2014.07.046","article-title":"Nox family NADPH oxidases: molecular mechanisms of activation","volume":"76","author":"Brandes","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.redox.2020.101638_bib18","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1007\/s00125-012-2557-6","article-title":"The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes","volume":"55","author":"Youn","year":"2012","journal-title":"Diabetologia"},{"key":"10.1016\/j.redox.2020.101638_bib19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.redox.2020.101638_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20031547","article-title":"Targeting of calcium\/calmodulin-dependent protein kinase II","volume":"378","author":"Colbran","year":"2004","journal-title":"Biochem. J."},{"key":"10.1016\/j.redox.2020.101638_bib21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/cvr\/cvm010","article-title":"CaM Kinase II-dependent pathophysiological signalling in endothelial cells","volume":"77","author":"Cai","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.redox.2020.101638_bib22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cardiores.2005.06.021","article-title":"Hydrogen peroxide regulation of endothelial function: origins, mechanisms, and consequences","volume":"68","author":"Cai","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.redox.2020.101638_bib23","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.109.204172","article-title":"Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+-calmodulin protein kinase II and promotes a death pathway conserved across different species","volume":"105","author":"Palomeque","year":"2009","journal-title":"Circ. Res."},{"key":"10.1016\/j.redox.2020.101638_bib24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.febslet.2004.06.061","article-title":"Role of CaMKII in hydrogen peroxide activation of ERK1\/2, p38 MAPK, HSP27 and actin reorganization in endothelial cells","volume":"572","author":"Nguyen","year":"2004","journal-title":"FEBS Lett."},{"key":"10.1016\/j.redox.2020.101638_bib25","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3389\/fphar.2017.00292","article-title":"Myosin light chain kinase: a potential target for treatment of inflammatory diseases","volume":"8","author":"Xiong","year":"2017","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.redox.2020.101638_bib26","article-title":"Contributions of myosin light chain kinase to regulation of epithelial paracellular permeability and mucosal homeostasis","volume":"21","author":"He","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.redox.2020.101638_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2019.109485","article-title":"Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease","volume":"66","author":"Cong","year":"2020","journal-title":"Cell. Signal."},{"key":"10.1016\/j.redox.2020.101638_bib28","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bbamem.2007.08.017","article-title":"Transmembrane proteins of tight junctions","volume":"1778","author":"Chiba","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.redox.2020.101638_bib29","first-page":"564","article-title":"Tight junctions: from simple barriers to multifunctional molecular gates, Nature reviews","volume":"17","author":"Zihni","year":"2016","journal-title":"Mole. Cell Biol."},{"key":"10.1016\/j.redox.2020.101638_bib30","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1152\/physrev.00035.2003","article-title":"Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis","volume":"84","author":"Bazzoni","year":"2004","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.redox.2020.101638_bib31","article-title":"Survival probabilities (the Kaplan-Meier method)","volume":"317","author":"Bland","year":"1998","journal-title":"BMJ (Clin. Res. Ed.)"},{"key":"10.1016\/j.redox.2020.101638_bib32","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/ki.2008.217","article-title":"The analysis of survival data: the Kaplan-Meier method","volume":"74","author":"Jager","year":"2008","journal-title":"Kidney Int."},{"key":"10.1016\/j.redox.2020.101638_bib33","doi-asserted-by":"crossref","first-page":"L297","DOI":"10.1152\/ajplung.00305.2016","article-title":"Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury","volume":"312","author":"Palumbo","year":"2017","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.redox.2020.101638_bib34","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1172\/JCI94495","article-title":"Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury","volume":"127","author":"Cheng","year":"2017","journal-title":"J. Clin. Invest."},{"issue":"85","key":"10.1016\/j.redox.2020.101638_bib35","first-page":"51300","article-title":"Electric cell-substrate impedance sensing for the quantification of endothelial proliferation, barrier function, and motility","author":"Szulcek","year":"2014","journal-title":"J. Visualized Exp. JoVE"},{"key":"10.1016\/j.redox.2020.101638_bib36","doi-asserted-by":"crossref","first-page":"8653","DOI":"10.1074\/jbc.M115.713149","article-title":"Differential roles of protein complexes NOX1-NOXO1 and NOX2-p47phox in mediating endothelial redox responses to oscillatory and unidirectional laminar shear stress","volume":"291","author":"Siu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.redox.2020.101638_bib37","doi-asserted-by":"crossref","first-page":"118","DOI":"10.2337\/db06-0288","article-title":"Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice","volume":"56","author":"Oak","year":"2007","journal-title":"Diabetes"},{"key":"10.1016\/j.redox.2020.101638_bib38","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.yjmcc.2014.07.005","article-title":"Netrin-1 abrogates ischemia\/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS","volume":"78","author":"Siu","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.redox.2020.101638_bib39","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1161\/hh0901.089987","article-title":"Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice","volume":"88","author":"Wang","year":"2001","journal-title":"Circ. Res."},{"key":"10.1016\/j.redox.2020.101638_bib40","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1161\/CIRCULATIONAHA.105.573709","article-title":"Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice","volume":"112","author":"Matsuno","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.redox.2020.101638_bib41","doi-asserted-by":"crossref","first-page":"5991","DOI":"10.1128\/IAI.69.10.5991-5996.2001","article-title":"Impaired pulmonary NF-kappaB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice","volume":"69","author":"Koay","year":"2001","journal-title":"Infect. Immun."},{"key":"10.1016\/j.redox.2020.101638_bib42","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.2353\/ajpath.2008.070765","article-title":"Genetic ablation of NADPH oxidase enhances susceptibility to cigarette smoke-induced lung inflammation and emphysema in mice","volume":"172","author":"Yao","year":"2008","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.redox.2020.101638_bib43","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1091\/mbc.e09-10-0876","article-title":"Abl tyrosine kinase phosphorylates nonmuscle Myosin light chain kinase to regulate endothelial barrier function","volume":"21","author":"Dudek","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.redox.2020.101638_bib44","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1165\/rcmb.2009-0197OC","article-title":"Non-muscle myosin light chain kinase isoform is a viable molecular target in acute inflammatory lung injury","volume":"44","author":"Mirzapoiazova","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.redox.2020.101638_bib45","doi-asserted-by":"crossref","first-page":"9360","DOI":"10.1074\/jbc.M111.294546","article-title":"Novel role for non-muscle myosin light chain kinase (MLCK) in hyperoxia-induced recruitment of cytoskeletal proteins, NADPH oxidase activation, and reactive oxygen species generation in lung endothelium","volume":"287","author":"Usatyuk","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.redox.2020.101638_bib46","doi-asserted-by":"crossref","DOI":"10.1177\/2045894018764171","article-title":"Myosin light chain kinase (MYLK) coding polymorphisms modulate human lung endothelial cell barrier responses via altered tyrosine phosphorylation, spatial localization, and lamellipodial protrusions","volume":"8","author":"Wang","year":"2018","journal-title":"Pulm. Circ."},{"key":"10.1016\/j.redox.2020.101638_bib47","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.bbamem.2007.07.012","article-title":"Adherens and tight junctions: structure, function and connections to the actin cytoskeleton","volume":"1778","author":"Hartsock","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.redox.2020.101638_bib48","first-page":"L647","article-title":"Structure, function, and regulation of cellular tight junctions","volume":"262","author":"Schneeberger","year":"1992","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.redox.2020.101638_bib49","doi-asserted-by":"crossref","DOI":"10.1038\/srep13262","article-title":"CaMKII regulates the strength of the epithelial barrier","volume":"5","author":"Shiomi","year":"2015","journal-title":"Sci. Rep."}],"updated-by":[{"DOI":"10.1016\/j.redox.2021.102200","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000}}],"container-title":["Redox Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213231720308430?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213231720308430?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:26:33Z","timestamp":1784906793000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213231720308430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":49,"alternative-id":["S2213231720308430"],"URL":"https:\/\/doi.org\/10.1016\/j.redox.2020.101638","relation":{},"ISSN":["2213-2317"],"issn-type":[{"value":"2213-2317","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII\/ERK1\/2\/MLCK and endothelial cell barrier dysfunction","name":"articletitle","label":"Article Title"},{"value":"Redox Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.redox.2020.101638","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"101638"}}