{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:50:31Z","timestamp":1791924631850,"version":"4.3.4"},"reference-count":104,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"45","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,11,7]]},"abstract":"<jats:p>Lung resident immune cells are essential for initiating defenses against inhaled air pollutants, including nanoparticles (NPs), which contribute to pulmonary disease progression. Here, lung intravital microscopy was used to examine the pulmonary innate immune responses in mice, during acute aerosol exposure to carbon NPs, a common environmental pollutant, or fluorescent quantum dot NPs. We found that inhaled NPs triggered rapid, neutrophil recruitment, localized to alveolar NP deposition hotspots, orchestrated by alveolar macrophages (AMs) through both their motility and phagocytic activity. AM motility inhibition in the alveoli via intercellular adhesion molecule\u20131\/LFA-1 blockade reduced neutrophil recruitment, as did impaired AM phagocytosis through C5a receptor 1\/Fc-\u03b3 receptor I inhibition or by stealth NP surfaces. In addition, cellular degranulation inhibition indicated the importance of spatially focused cytokine release in neutrophil recruitment. Collectively, our study elucidates AM-epithelial interactions as a critical key event for NPs triggered neutrophilia, with AM motility and phagocytosis driving recruitment and site-specific immune responses in the alveolar microenvironment.<\/jats:p>","DOI":"10.1126\/sciadv.adx8586","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:58:33Z","timestamp":1762541913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Alveolar macrophages initiate the spatially targeted recruitment of neutrophils after nanoparticle inhalation"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6113-6057","authenticated-orcid":true,"given":"Qiongliang","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."},{"name":"Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-776X","authenticated-orcid":true,"given":"Lianyong","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet","family":"Wilmot","sequence":"additional","affiliation":[{"name":"Louvain Center for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Exp\u00e9rimental et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Louvain-la-Neuve, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Leinardi","sequence":"additional","affiliation":[{"name":"Louvain Center for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Exp\u00e9rimental et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Louvain-la-Neuve, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoxia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schr\u00f6ppel","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0154-2357","authenticated-orcid":true,"given":"David","family":"Kutschke","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0005-3535","authenticated-orcid":true,"given":"Judith","family":"Secklehner","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Institute, Glasgow, UK."},{"name":"School of Cancer Sciences, University of Glasgow, Glasgow, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-480X","authenticated-orcid":true,"given":"Ali \u00d6nder","family":"Yldirim","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Huaux","sequence":"additional","affiliation":[{"name":"Louvain Center for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Exp\u00e9rimental et Clinique (IREC), Universit\u00e9 Catholique de Louvain, Louvain-la-Neuve, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Zeuschner","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Max Planck Institute for Molecular Biomedicine, Muenster, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7172-5234","authenticated-orcid":true,"given":"Leo M.","family":"Carlin","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Institute, Glasgow, UK."},{"name":"School of Cancer Sciences, University of Glasgow, Glasgow, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7689-3613","authenticated-orcid":true,"given":"Markus","family":"Sperandio","sequence":"additional","affiliation":[{"name":"Walter Brendel Centre of Experimental Medicine, Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Planegg-Martinsried, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-7786","authenticated-orcid":true,"given":"Otmar","family":"Schmid","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-0389","authenticated-orcid":true,"given":"Tobias","family":"Stoeger","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-6332","authenticated-orcid":true,"given":"Markus","family":"Rehberg","sequence":"additional","affiliation":[{"name":"Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.10.1127"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.7339"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01471.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2017.02.014"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2015.12.006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00071205"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-016-0144-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-017-0200-x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.0c00051"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.06.040"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.8b01062"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2010.44"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.38659"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13040"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00964-2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-4-4"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.11370"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3600"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.09.007"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-021-00432-z"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.06.006"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00113"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00832-3"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aam8929"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1806265115"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.020"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16985"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/nl102100m"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2017-0350"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.11.73"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfp087"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202404661"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131199"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3052"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.46.2.119"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.121321"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/cnm.3215"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48753-6"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep08760"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01986580"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1848"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.12.017"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2156"},{"key":"e_1_3_2_45_2","first-page":"L476","article-title":"Regulation of alveolar epithelial cell ICAM-1 expression by cell shape and cell-cell interactions","volume":"266","author":"Paine R.","year":"1994","unstructured":"R. Paine III, P. Christensen, G. B. Toews, R. H. Simon, Regulation of alveolar epithelial cell ICAM-1 expression by cell shape and cell-cell interactions. Am. J. Physiol. 266, L476\u2013L484 (1994).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-021-01437-2"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.336"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8128245"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.05.051"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201600071"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0479OC"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-202X(89)90069-9"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01966519"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3582"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03049"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.161.3.617"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.238097"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2020.104134"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00496"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2206"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00933-4"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.04594-2020"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.030992020"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2016.11.012"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-7-2"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-0394-0"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114397"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2021.0058"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54267-1"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108734"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1021\/nn402330b"},{"key":"e_1_3_2_73_2","doi-asserted-by":"crossref","unstructured":"I. Paur M. H. Carlsen B. L. Halvorsen R. Blomhoff \u201cAntioxidants in herbs and spices: Roles in oxidative stress and redox signaling \u201d in Herbal Medicine: Biomolecular and Clinical Aspects I. F. F. Benzie S. Wachtel-Galor Eds. (CRC Press\/Taylor and Francis 2011). pp. 27\u201336.","DOI":"10.1201\/b10787-3"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2013.08.004"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2000.9096"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c04111"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.869041"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2015.08.004"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220525"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344359"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.691957"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00442.2007"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-017-0223-3"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.10.009"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115816"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof7060484"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1530-5"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00227.2012"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.736692"},{"key":"e_1_3_2_90_2","doi-asserted-by":"crossref","unstructured":"C. Voss L. Han M. Ansari M. Strunz V. Haefner C. Ballester-Lopez I. Angelidis C. H. Mayr T. Berthing T. Conlon Q. Liu H. Ren Q. Zhou O. Schmid A. \u00d6. Yildirim M. Rehberg U. Vogel J. Gote-Schniering F. J. Theis H. B. Schiller T. Stoeger Cell circuits underlying nanomaterial specific respiratory toxicology. bioRxiv 2024.02.10.579746 [Preprint] (2024). https:\/\/doi.org\/10.1101\/2024.02.10.579746.","DOI":"10.1101\/2024.02.10.579746"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb13009.x"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.7.3429"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-016-0558-0"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.4.2448"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4289-4296.2000"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b03190"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.152952"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S146192"},{"key":"e_1_3_2_99_2","first-page":"1029","article-title":"Three-dimensional quantitative co-mapping of pulmonary morphology and nanoparticle distribution with cellular resolution in nondissected murine lungs","volume":"13","author":"Yang L.","year":"2019","unstructured":"L. Yang, A. Feuchtinger, W. M\u00f6ller, Y. Ding, D. Kutschke, G. M\u00f6ller, J. C. Schittny, G. Burgstaller, W. Hofmann, T. Stoeger, R. Daniel, A. Walch, O. Schmid, Three-dimensional quantitative co-mapping of pulmonary morphology and nanoparticle distribution with cellular resolution in nondissected murine lungs. ACS Nano 13, 1029\u20131041 (2019).","journal-title":"ACS Nano"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-021-00419-w"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-6-31"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-8-111"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313545"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1038\/318667a0"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28809-4"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adx8586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:58:34Z","timestamp":1762541914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adx8586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":104,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2025,11,7]]}},"alternative-id":["10.1126\/sciadv.adx8586"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adx8586","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]},"assertion":[{"value":"2025-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx8586"}}