{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:25:22Z","timestamp":1786116322208,"version":"build-2736575974"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infection remains a major challenge in donor lung management and post-transplant respiratory care, particularly in the setting of antimicrobial resistance. Ex vivo lung perfusion (EVLP) provides an opportunity for localized antimicrobial intervention before transplantation and allows detailed assessment of infection-associated lung injury under controlled conditions. In this study, we evaluated inhaled sphingosine in a porcine EVLP model of acute\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    airway contamination using three experimental groups: uninfected controls, infected lungs treated with 0.9% NaCl, and infected lungs treated with sphingosine. This design allowed us to assess both the impact of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    infection on EVLP physiology and the effects of sphingosine on bacterial burden and infection-associated lung changes. Infected porcine lungs showed greater declines in dynamic and static compliance than uninfected controls, whereas pulmonary artery pressure, peak airway pressure, oxygen-exchange capacity, lactate accumulation, lung weight gain, and histological injury scores were not significantly worsened under the present experimental conditions. Inhaled sphingosine reduced bronchial\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    CFU counts, whereas 0.9% NaCl did not. Sphingosine treatment did not further impair lung physiology, oxygenation, lactate accumulation, histological injury, or lung weight gain. Mechanistic analyses showed association of sphingosine with bacterial cardiolipin and increased colocalization of sphingosine with\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    , consistent with a membrane-associated antibacterial mechanism described in previous studies. In exploratory experiments using four explanted human recipient lungs, sphingosine inhalation increased sphingosine levels in bronchial and parenchymal tissue and altered related sphingolipid metabolites, including sphingosine-1-phosphate, ceramide, and sphingomyelin, without apparent acute histological damage in assessed airway samples. One of the four human specimens showed bacterial colonization, in which a marked reduction in detectable bacterial growth after sphingosine inhalation was observed as a hypothesis-generating finding. Together, these data suggest that inhaled sphingosine can reduce acutely accessible bronchial\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    burden during porcine EVLP without detectable short-term adverse effects and provide a basis for further investigation of sphingosine-related lipid metabolism and local antimicrobial strategies during EVLP.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-65074-7","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:26:00Z","timestamp":1786008360000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhaled sphingosine reduces bronchial Pseudomonas aeruginosa burden during porcine ex vivo lung perfusion and shows tissue delivery in explanted human lungs"],"prefix":"10.1038","volume":"16","author":[{"given":"Yongjie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Leukers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Schimank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Abou-Issa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Taube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wissmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Pizanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kamler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"issue":"18","key":"65074_CR1","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","volume":"81","author":"D Reynolds","year":"2021","unstructured":"Reynolds, D. & Kollef, M. The epidemiology and pathogenesis and treatment of Pseudomonas aeruginosa infections: An update. Drugs 81(18), 2117\u20132131. https:\/\/doi.org\/10.1007\/s40265-021-01635-6 (2021).","journal-title":"Drugs"},{"issue":"11","key":"65074_CR2","doi-asserted-by":"publisher","first-page":"6654","DOI":"10.21037\/jtd-2021-12","volume":"13","author":"M McCort","year":"2021","unstructured":"McCort, M., MacKenzie, E., Pursell, K. & Pitrak, D. Bacterial infections in lung transplantation. J. Thorac. Dis. 13(11), 6654\u20136672. https:\/\/doi.org\/10.21037\/jtd-2021-12 (2021).","journal-title":"J. Thorac. Dis."},{"issue":"3","key":"65074_CR3","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1183\/09031936.00095214","volume":"45","author":"J Riera","year":"2015","unstructured":"Riera, J. et al. Ventilator-associated respiratory infection following lung transplantation. Eur. Respir. J. 45(3), 726\u2013737. https:\/\/doi.org\/10.1183\/09031936.00095214 (2015).","journal-title":"Eur. Respir. J."},{"issue":"4","key":"65074_CR4","doi-asserted-by":"publisher","first-page":"2001720","DOI":"10.1183\/13993003.01720-2020","volume":"56","author":"B De Muynck","year":"2020","unstructured":"De Muynck, B. et al. Successful Pseudomonas aeruginosa eradication improves outcomes after lung transplantation: A retrospective cohort analysis. Eur. Respir. J. 56(4), 2001720. https:\/\/doi.org\/10.1183\/13993003.01720-2020 (2020).","journal-title":"Eur. Respir. J."},{"issue":"1","key":"65074_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01056-1","volume":"7","author":"S Qin","year":"2022","unstructured":"Qin, S. et al. Pseudomonas aeruginosa: Pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics. Signal Transduct. Target. Ther. 7(1), 199. https:\/\/doi.org\/10.1038\/s41392-022-01056-1 (2022).","journal-title":"Signal Transduct. Target. Ther."},{"issue":"11","key":"65074_CR6","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1017\/ice.2016.174","volume":"37","author":"LM Weiner","year":"2011","unstructured":"Weiner, L. M. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect. Control Hosp. Epidemiol. 37(11), 1288\u20131301. https:\/\/doi.org\/10.1017\/ice.2016.174 (2011).","journal-title":"Infect. Control Hosp. Epidemiol."},{"issue":"1","key":"65074_CR7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/tid.12471","volume":"18","author":"G Tebano","year":"2016","unstructured":"Tebano, G. et al. Epidemiology and risk factors of multidrug-resistant bacteria in respiratory samples after lung transplantation. Transpl. Infect. Dis. 18(1), 22\u201330. https:\/\/doi.org\/10.1111\/tid.12471 (2016).","journal-title":"Transpl. Infect. Dis."},{"issue":"1","key":"65074_CR8","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.biotechadv.2018.11.013","volume":"37","author":"Z Pang","year":"2019","unstructured":"Pang, Z., Raudonis, R., Glick, B. R., Lin, T. J. & Cheng, Z. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies. Biotechnol. Adv. 37(1), 177\u2013192. https:\/\/doi.org\/10.1016\/j.biotechadv.2018.11.013 (2019).","journal-title":"Biotechnol. Adv."},{"issue":"9","key":"65074_CR9","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.15252\/emmm.201404075","volume":"6","author":"Y Pewzner-Jung","year":"2014","unstructured":"Pewzner-Jung, Y. et al. Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa. EMBO Mol. Med. 6(9), 1205\u20131214. https:\/\/doi.org\/10.15252\/emmm.201404075 (2014).","journal-title":"EMBO Mol. Med."},{"issue":"3","key":"65074_CR10","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1128\/AAC.05151-11","volume":"56","author":"CL Fischer","year":"2012","unstructured":"Fischer, C. L. et al. Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria. Antimicrob. Agents Chemother. 56(3), 1157\u20131161. https:\/\/doi.org\/10.1128\/AAC.05151-11 (2012).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"1","key":"65074_CR11","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1159\/000343175","volume":"26","author":"CL Fischer","year":"2013","unstructured":"Fischer, C. L. et al. Sphingoid bases are taken up by Escherichia coli and Staphylococcus aureus and induce ultrastructural damage. Skin Pharmacol. Physiol. 26(1), 36\u201344. https:\/\/doi.org\/10.1159\/000343175 (2013).","journal-title":"Skin Pharmacol. Physiol."},{"issue":"3","key":"65074_CR12","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1111\/1523-1747.ep12497842","volume":"98","author":"DJ Bibel","year":"1992","unstructured":"Bibel, D. J., Aly, R. & Shinefield, H. R. Antimicrobial activity of sphingosines. J. Invest. Dermatol. 98(3), 269\u2013273. https:\/\/doi.org\/10.1111\/1523-1747.ep12497842 (1992).","journal-title":"J. Invest. Dermatol."},{"issue":"2","key":"65074_CR13","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00109-019-01858-x","volume":"98","author":"S Beck","year":"2020","unstructured":"Beck, S. et al. Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro. J Mol Med (Berl) 98(2), 209\u2013219. https:\/\/doi.org\/10.1007\/s00109-019-01858-x (2020).","journal-title":"J Mol Med (Berl)"},{"key":"65074_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00215","volume":"10","author":"F Solger","year":"2020","unstructured":"Solger, F. et al. A role of sphingosine in the intracellular survival of Neisseria gonorrhoeae. Front. Cell. Infect. Microbiol. 10, 215. https:\/\/doi.org\/10.3389\/fcimb.2020.00215 (2020).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"65074_CR15","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.jss.2017.06.042","volume":"219","author":"TC Rice","year":"2017","unstructured":"Rice, T. C. et al. Sphingosine rescues aged mice from pulmonary pseudomonas infection. J. Surg. Res. 219, 354\u2013359. https:\/\/doi.org\/10.1016\/j.jss.2017.06.042 (2017).","journal-title":"J. Surg. Res."},{"key":"65074_CR16","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.2147\/IDR.S407335","volume":"16","author":"Q Qi","year":"2023","unstructured":"Qi, Q. et al. Decreased sphingosine due to down-regulation of acid ceramidase expression in airway of bronchiectasis patients: A potential contributor to Pseudomonas aeruginosa infection. Infect Drug Resist. 16, 2573\u20132588. https:\/\/doi.org\/10.2147\/IDR.S407335 (2023).","journal-title":"Infect Drug Resist."},{"issue":"22","key":"65074_CR17","doi-asserted-by":"publisher","first-page":"7686","DOI":"10.1074\/jbc.RA119.012325","volume":"295","author":"R Verhaegh","year":"2020","unstructured":"Verhaegh, R., Becker, K. A., Edwards, M. J. & Gulbins, E. Sphingosine kills bacteria by binding to cardiolipin. J. Biol. Chem. 295(22), 7686\u20137696. https:\/\/doi.org\/10.1074\/jbc.RA119.012325 (2020).","journal-title":"J. Biol. Chem."},{"issue":"15","key":"65074_CR18","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1056\/NEJMoa1014597","volume":"364","author":"M Cypel","year":"2011","unstructured":"Cypel, M. et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N. Engl. J. Med. 364(15), 1431\u20131440. https:\/\/doi.org\/10.1056\/NEJMoa1014597 (2011).","journal-title":"N. Engl. J. Med."},{"issue":"4","key":"65074_CR19","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1111\/ajt.13562","volume":"16","author":"D Nakajima","year":"2016","unstructured":"Nakajima, D. et al. Ex vivo perfusion treatment of infection in human donor lungs. Am. J. Transplant. 16(4), 1229\u20131237. https:\/\/doi.org\/10.1111\/ajt.13562 (2016).","journal-title":"Am. J. Transplant."},{"issue":"6","key":"65074_CR20","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.33594\/000000194","volume":"53","author":"H Carstens","year":"2019","unstructured":"Carstens, H. et al. Clinical development of sphingosine as anti-bacterial drug: Inhalation of sphingosine in mini pigs has no adverse side effects. Cell Physiol Biochem. 53(6), 1015\u20131028. https:\/\/doi.org\/10.33594\/000000194 (2019).","journal-title":"Cell Physiol Biochem."},{"issue":"1","key":"65074_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-97708-3","volume":"11","author":"H Carstens","year":"2021","unstructured":"Carstens, H. et al. Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs. Sci. Rep. 11(1), 18607. https:\/\/doi.org\/10.1038\/s41598-021-97708-3 (2021).","journal-title":"Sci. Rep."},{"issue":"7","key":"65074_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0271620","volume":"17","author":"H Carstens","year":"2022","unstructured":"Carstens, H. et al. Antimicrobial effects of inhaled sphingosine against Pseudomonas aeruginosa in isolated ventilated and perfused pig lungs. PLoS ONE 17(7), e0271620. https:\/\/doi.org\/10.1371\/journal.pone.0271620 (2022).","journal-title":"PLoS ONE"},{"issue":"13","key":"65074_CR23","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1089\/ars.2014.5979","volume":"22","author":"A Manag\u00f2","year":"2015","unstructured":"Manag\u00f2, A. et al. Pseudomonas aeruginosa pyocyanin induces neutrophil death via mitochondrial reactive oxygen species and mitochondrial acid sphingomyelinase. Antioxid. Redox Signal. 22(13), 1097\u20131110. https:\/\/doi.org\/10.1089\/ars.2014.5979 (2015).","journal-title":"Antioxid. Redox Signal."},{"issue":"5","key":"65074_CR24","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1165\/rcmb.2009-0210ST","volume":"44","author":"G Matute-Bello","year":"2011","unstructured":"Matute-Bello, G. et al. An official American Thoracic Society workshop report: Features and measurements of experimental acute lung injury in animals. Am. J. Respir. Cell Mol. Biol. 44(5), 725\u2013738. https:\/\/doi.org\/10.1165\/rcmb.2009-0210ST (2011).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"issue":"1","key":"65074_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83813-w","volume":"11","author":"S Peters","year":"2021","unstructured":"Peters, S. et al. Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria. Sci. Rep. 11(1), 4300. https:\/\/doi.org\/10.1038\/s41598-021-83813-w (2021).","journal-title":"Sci. Rep."},{"issue":"12","key":"65074_CR26","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1038\/s41380-018-0090-9","volume":"23","author":"A Gulbins","year":"2018","unstructured":"Gulbins, A. et al. Antidepressants act by inducing autophagy controlled by sphingomyelin\u2013ceramide. Mol. Psychiatry 23(12), 2324\u20132346. https:\/\/doi.org\/10.1038\/s41380-018-0090-9 (2018).","journal-title":"Mol. Psychiatry"},{"issue":"1","key":"65074_CR27","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1111\/j.1600-6143.2005.01145.x","volume":"6","author":"I Ruiz","year":"2006","unstructured":"Ruiz, I. et al. Donor-to-host transmission of bacterial and fungal infections in lung transplantation. Am. J. Transplant. 6(1), 178\u2013182. https:\/\/doi.org\/10.1111\/j.1600-6143.2005.01145.x (2006).","journal-title":"Am. J. Transplant."},{"issue":"6","key":"65074_CR28","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1152\/jappl.1990.69.6.2290","volume":"69","author":"K Byrne","year":"1985","unstructured":"Byrne, K. et al. Pulmonary compliance: Early assessment of evolving lung injury after onset of sepsis. J. Appl. Physiol. 69(6), 2290\u20132295. https:\/\/doi.org\/10.1152\/jappl.1990.69.6.2290 (1985).","journal-title":"J. Appl. Physiol."},{"issue":"6-7","key":"65074_CR29","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1515\/hsz-2014-0285","volume":"396","author":"AP Seitz","year":"2015","unstructured":"Seitz, A. P., Grassm\u00e9, H., Edwards, M. J., Pewzner-Jung, Y. & Gulbins, E. Ceramide and sphingosine in pulmonary infections. Biol. Chem. 396(6\u20137), 611\u2013620. https:\/\/doi.org\/10.1515\/hsz-2014-0285 (2015).","journal-title":"Biol. Chem."},{"issue":"6","key":"65074_CR30","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1189\/jlb.3HI0416-197R","volume":"100","author":"TC Rice","year":"2016","unstructured":"Rice, T. C., Seitz, A. P., Edwards, M. J., Gulbins, E. & Caldwell, C. C. Frontline science: Sphingosine rescues burn-injured mice from pulmonary Pseudomonas aeruginosa infection. J. Leukoc. Biol. 100(6), 1233\u20131237. https:\/\/doi.org\/10.1189\/jlb.3HI0416-197R (2016).","journal-title":"J. Leukoc. Biol."},{"issue":"6","key":"65074_CR31","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.chom.2017.05.001","volume":"21","author":"H Grassm\u00e9","year":"2017","unstructured":"Grassm\u00e9, H. et al. \u03b21-Integrin accumulates in cystic fibrosis luminal airway epithelial membranes and decreases sphingosine, promoting bacterial infections. Cell Host Microbe 21(6), 707\u2013718. https:\/\/doi.org\/10.1016\/j.chom.2017.05.001 (2017).","journal-title":"Cell Host Microbe"},{"issue":"4","key":"65074_CR32","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00591-24","volume":"93","author":"H Grassm\u00e9","year":"2025","unstructured":"Grassm\u00e9, H. et al. Sphingosine-mediated death of Pseudomonas aeruginosa involves degradation of cardiolipin by the maintenance of outer lipid asymmetry system. Infect. Immun. 93(4), e0059124. https:\/\/doi.org\/10.1128\/iai.00591-24 (2025).","journal-title":"Infect. Immun."},{"key":"65074_CR33","doi-asserted-by":"publisher","first-page":"ftae016","DOI":"10.1093\/femspd\/ftae016","volume":"82","author":"H May","year":"2024","unstructured":"May, H. et al. Sphingosine kills intracellular Pseudomonas aeruginosa and Staphylococcus aureus. Pathog Dis. 82, ftae016. https:\/\/doi.org\/10.1093\/femspd\/ftae016 (2024).","journal-title":"Pathog Dis."},{"issue":"1","key":"65074_CR34","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.healun.2023.08.021","volume":"43","author":"Y Liu","year":"2024","unstructured":"Liu, Y. et al. Treatment of Staphylococcus aureus infection with sphingosine in ex vivo perfused and ventilated lungs. J. Heart Lung Transplant. 43(1), 100\u2013110. https:\/\/doi.org\/10.1016\/j.healun.2023.08.021 (2024).","journal-title":"J. Heart Lung Transplant."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65074-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65074-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65074-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:40:56Z","timestamp":1786009256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65074-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["65074"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-65074-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]},"assertion":[{"value":"17 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors of this manuscript have no conflicts of interest to disclose.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The use of explanted human recipient lung material was permitted by Ethikkommission des Universit\u00e4tsklinikum Essen (West German Heart and Vascular Center Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany) under the number 17\u20137326-BO. Informed consent was obtained from all subjects and\/or their legal guardian(s). All animal procedures were conducted under the supervision of and approved by the Central Animal Laboratory of the University of Duisburg-Essen, following the Principles of Laboratory and Animal Care, the Guide for the Care and Use of Laboratory Animals, and the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments). Euthanasia was performed in accordance with the Animal Welfare Act (TierSchG).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"24315"}}