{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:15:29Z","timestamp":1785428129076,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,24]]},"group-title":"Pharmacology and Toxicology","reference-count":134,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["1RO1HL167048 (Pollard HB, PI)."],"award-info":[{"award-number":["1RO1HL167048 (Pollard HB, PI)."]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Abstract2<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sustained exposures to high atmospheric levels of PM2.5 at population scale are associated with increased risks for pulmonary inflammatory diseases. These are marked by activation of the TRPC6 (Transient Receptor Potential Canonical type 6) calcium channel, increased reactive oxygen species (ROS) and oxidative stress. Long term exposures are associated with reduced life span, and increased incidences of cardiovascular diseases, dementia, Parkinson\u2019s and Alzheimer disease, and increased risk of autism and autism spectrum disorders. It has been proposed that the PM2.5 toxin is benzo[a]pyrene (B[a]P) that is adsorbed to the surface of the PM2.5 particle.. But the mechanism by which B[a]P might drive pulmonary inflammatory diseases, or any other of the indications above, are not known.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Hypothesis<\/jats:title>\n                  <jats:p>\n                    B[a]P was recently reported to bind irreversibly and destructively to the \u03b22 Adrenergic Receptor (\u03b22AR) in the lung.\n                    <jats:italic>We<\/jats:italic>\n                    have therefore hypothesized that B[a]P is the adsorbed PM2.5 toxin, and that \u03b22AR is the B[a]P receptor responsible for TRPC6 activation in lung epithelial cells.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    To test this hypothesis, we exposed a polarized organoid model of normal human lung epithelia, polarized lung epithelial 16HBE14o-cells, and tracheobronchial slice cultures from ferret lung to either PM2.5 or B[a]P. We found that both PM2.5 and B[a]P: (i) irreversibly activated of \u03b22AR signaling via G\n                    <jats:sub>i<\/jats:sub>\n                    to PI3K\/AKT; (ii) increased NF\u03baB-activated release of proinflammatory cytokines through IKK\u03b1\u03b2 activation by PI3K\/AKT, which was suppressed by the PI3K inhibitor LY 294002 (iii) desensitized and destroyed the activated \u03b22AR receptor by endocytic recycling; (iv) also destroyed \u03b22AR\u2019s signalplex partner CFTR by the same process; (v) activated the CFTR-bound calcium channel protein TRPC6 due to loss of inhibitory CFTR; leading to (vi) increased cytosolic [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] concentration; (vii) increased ROS due to mitochondrial uncoupling; and (viii) increased expression of oxidative stress. Treatment with the TRPC6 inhibitor BI 749327 blocked steps (vi-viii), and preserved CFTR from endocytic loss. Treatment of tracheobronchial slice cultures of ferret lung with either PM2.5 or B[a]P resulted in increased secretion of IL-6, increased expression of TRPC6, and reduced expression of \u03b22AR and CFTR. Finally, we found that exposure of lung organoids to B[a]P significantly reduced expression of the same five microRNAs (miR-126a-3p, miR-30b-5p, miR-103a-3p, miR-26a-5p, and miR-766-3p) previously identified in sera from service members exposed to PM2.5 from burn pit emissions during deployment to Iraq and Afghanistan.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>PM2.5 and the PM2.5 toxin benzo[a]pyrene (B[a]P) induce inflammation and oxidative stress in the airway by increased expression of TRPC6 and inactivation of \u03b22AR\/CFTR signaling. These discoveries mark the first identification of a mechanism by which exposure to PM2.5 or the PM2.5 toxin B[a]P itself can induce inflammation and TRPC6-dependent oxidative stress in lung epithelia.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.21.719931","type":"posted-content","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:30:13Z","timestamp":1777048213000},"source":"Crossref","is-referenced-by-count":0,"title":["PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of \u03b22AR\/CFTR signaling"],"prefix":"10.64898","author":[{"given":"Hung","family":"Caohuy","sequence":"first","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mungunsukh","family":"Ognoon","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"},{"name":"Center for Military Precision Health (CMPH), Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for the Study of Traumatic Stress (CSTS), Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thalia","family":"Dib","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bette S.","family":"Pollard","sequence":"additional","affiliation":[{"name":"Silver Pharmaceuticals, Rockville, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naheed","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Flagg","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmendra K.","family":"Soni","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"},{"name":"Amity Institute of Biotechnology, Amity University, Haryana Gurugram, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopa","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Rittase","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver J","family":"L\u2019Esperance","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Juliano","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey B.","family":"Pollard","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics (APG), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042808350724000_2026.04.21.719931v1.1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2072-1439.2016.01.19"},{"key":"2026042808350724000_2026.04.21.719931v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.105895"},{"key":"2026042808350724000_2026.04.21.719931v1.3","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.882569"},{"key":"2026042808350724000_2026.04.21.719931v1.4","doi-asserted-by":"publisher","DOI":"10.1172\/jci194312"},{"key":"2026042808350724000_2026.04.21.719931v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000297"},{"key":"2026042808350724000_2026.04.21.719931v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30505-6"},{"key":"2026042808350724000_2026.04.21.719931v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.978475"},{"key":"2026042808350724000_2026.04.21.719931v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09956-x"},{"key":"2026042808350724000_2026.04.21.719931v1.9","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1288"},{"key":"2026042808350724000_2026.04.21.719931v1.10","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1134341"},{"key":"2026042808350724000_2026.04.21.719931v1.11","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.123.066017"},{"key":"2026042808350724000_2026.04.21.719931v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2022.100208"},{"key":"2026042808350724000_2026.04.21.719931v1.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2211282119"},{"key":"2026042808350724000_2026.04.21.719931v1.14","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.3300"},{"key":"2026042808350724000_2026.04.21.719931v1.15","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.4058"},{"key":"2026042808350724000_2026.04.21.719931v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/s2542-5196(20)30227-8"},{"key":"2026042808350724000_2026.04.21.719931v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004912"},{"key":"2026042808350724000_2026.04.21.719931v1.18","doi-asserted-by":"publisher","DOI":"10.1186\/s13584-026-00753-4"},{"key":"2026042808350724000_2026.04.21.719931v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41370-024-00647-0"},{"key":"2026042808350724000_2026.04.21.719931v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2025.123378"},{"key":"2026042808350724000_2026.04.21.719931v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.113307"},{"key":"2026042808350724000_2026.04.21.719931v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161851"},{"key":"2026042808350724000_2026.04.21.719931v1.23","doi-asserted-by":"publisher","DOI":"10.1289\/ehp9509"},{"key":"2026042808350724000_2026.04.21.719931v1.24","unstructured":"NAAQSssss. EPA.gov 2025. Available from: epa.gov\/criteria-air-pollutants\/naaqs-table."},{"key":"2026042808350724000_2026.04.21.719931v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfac001"},{"key":"2026042808350724000_2026.04.21.719931v1.26","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.46421"},{"key":"2026042808350724000_2026.04.21.719931v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102587"},{"key":"2026042808350724000_2026.04.21.719931v1.28","doi-asserted-by":"publisher","DOI":"10.3390\/nano12152656"},{"key":"2026042808350724000_2026.04.21.719931v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2024.125275"},{"key":"2026042808350724000_2026.04.21.719931v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.113066"},{"key":"2026042808350724000_2026.04.21.719931v1.31","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7394"},{"key":"2026042808350724000_2026.04.21.719931v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2021.09.010"},{"key":"2026042808350724000_2026.04.21.719931v1.33","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph13080748"},{"key":"2026042808350724000_2026.04.21.719931v1.34","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.967174"},{"key":"2026042808350724000_2026.04.21.719931v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-70646-6"},{"key":"2026042808350724000_2026.04.21.719931v1.36","doi-asserted-by":"publisher","DOI":"10.1186\/1556-276X-9-532"},{"key":"2026042808350724000_2026.04.21.719931v1.37","doi-asserted-by":"publisher","DOI":"10.1093\/aob\/mcm247"},{"key":"2026042808350724000_2026.04.21.719931v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-26615-y"},{"key":"2026042808350724000_2026.04.21.719931v1.39","doi-asserted-by":"publisher","DOI":"10.1177\/1091581816682224"},{"issue":"27","key":"2026042808350724000_2026.04.21.719931v1.40","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.1016\/j.atmosenv.2007.02.042","article-title":"Exploring relationships between outdoor air particulate-associated polycyclic aromatic hydrocarbon and PM2.5: A case study of benzo(a)pyrene in California metropolitan regions","volume":"41","year":"2007","journal-title":"Atmospheric Environment"},{"key":"2026042808350724000_2026.04.21.719931v1.41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116348"},{"key":"2026042808350724000_2026.04.21.719931v1.42","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.redox.2017.07.001","article-title":"Metabolomics analysis reveals that benzo[a]pyrene, a component of PM2.5, promotes pulmonary injury by modifying lipid metabolism in a phospholipase A2-dependent manner in vivo and in vitro","volume":"13","year":"2017","journal-title":"Redox Biology"},{"key":"2026042808350724000_2026.04.21.719931v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/0045-6535(95)00348-7"},{"key":"2026042808350724000_2026.04.21.719931v1.44","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-2089-9"},{"key":"2026042808350724000_2026.04.21.719931v1.45","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4017"},{"key":"2026042808350724000_2026.04.21.719931v1.46","doi-asserted-by":"publisher","DOI":"10.1186\/s12940-021-00711-4"},{"key":"2026042808350724000_2026.04.21.719931v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101530"},{"key":"2026042808350724000_2026.04.21.719931v1.48","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1980.60.4.1107"},{"key":"2026042808350724000_2026.04.21.719931v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/303468a0"},{"key":"2026042808350724000_2026.04.21.719931v1.50","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2018.8355"},{"key":"2026042808350724000_2026.04.21.719931v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanplh.2025.101334"},{"key":"2026042808350724000_2026.04.21.719931v1.52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.643260"},{"key":"2026042808350724000_2026.04.21.719931v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2009.05.011"},{"key":"2026042808350724000_2026.04.21.719931v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2021.104179"},{"key":"2026042808350724000_2026.04.21.719931v1.55","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-014-0048-8"},{"key":"2026042808350724000_2026.04.21.719931v1.56","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs002"},{"key":"2026042808350724000_2026.04.21.719931v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2017.07.028"},{"key":"2026042808350724000_2026.04.21.719931v1.58","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00712"},{"key":"2026042808350724000_2026.04.21.719931v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03646-4"},{"key":"2026042808350724000_2026.04.21.719931v1.60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0135434100"},{"key":"2026042808350724000_2026.04.21.719931v1.61","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402030101"},{"key":"2026042808350724000_2026.04.21.719931v1.62","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0347OC"},{"key":"2026042808350724000_2026.04.21.719931v1.63","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27165324"},{"key":"2026042808350724000_2026.04.21.719931v1.64","doi-asserted-by":"publisher","DOI":"10.3390\/ph18060784"},{"key":"2026042808350724000_2026.04.21.719931v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2019.05.007"},{"key":"2026042808350724000_2026.04.21.719931v1.66","doi-asserted-by":"publisher","DOI":"10.1007\/s00244-014-0077-8"},{"key":"2026042808350724000_2026.04.21.719931v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2020.06.005"},{"key":"2026042808350724000_2026.04.21.719931v1.68","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052783"},{"key":"2026042808350724000_2026.04.21.719931v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2360-0"},{"key":"2026042808350724000_2026.04.21.719931v1.70","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111355"},{"key":"2026042808350724000_2026.04.21.719931v1.71","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01808-3"},{"key":"2026042808350724000_2026.04.21.719931v1.72","doi-asserted-by":"publisher","DOI":"10.1007\/s10653-025-02578-7"},{"key":"2026042808350724000_2026.04.21.719931v1.73","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93029"},{"key":"2026042808350724000_2026.04.21.719931v1.74","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00296.2015"},{"key":"2026042808350724000_2026.04.21.719931v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-66473-4"},{"key":"2026042808350724000_2026.04.21.719931v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2006.09.002"},{"key":"2026042808350724000_2026.04.21.719931v1.77","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.123.000831"},{"key":"2026042808350724000_2026.04.21.719931v1.78","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00287.2020"},{"key":"2026042808350724000_2026.04.21.719931v1.79","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-017-0557-2"},{"key":"2026042808350724000_2026.04.21.719931v1.80","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0263OC"},{"key":"2026042808350724000_2026.04.21.719931v1.81","doi-asserted-by":"publisher","DOI":"10.1097\/jom.0000000000000764"},{"key":"2026042808350724000_2026.04.21.719931v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2023.06.012"},{"key":"2026042808350724000_2026.04.21.719931v1.83","unstructured":"Butler DA , Styka AN, DA S . Assessment of Department of Veterans Affairs Airborn Hazards and Open Burn Pit Registry, Chapter 5. Analysis and Interpretation of Exposures data,: National Academy of Sciences, Engineering and Medicine; 2017."},{"key":"2026042808350724000_2026.04.21.719931v1.84","doi-asserted-by":"publisher","DOI":"10.1097\/jom.0000000000001692"},{"key":"2026042808350724000_2026.04.21.719931v1.85","doi-asserted-by":"publisher","DOI":"10.1097\/jom.0000000000000768"},{"key":"2026042808350724000_2026.04.21.719931v1.86","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43052"},{"key":"2026042808350724000_2026.04.21.719931v1.87","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06549-9"},{"key":"2026042808350724000_2026.04.21.719931v1.88","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2424470122"},{"key":"2026042808350724000_2026.04.21.719931v1.89","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.259002"},{"key":"2026042808350724000_2026.04.21.719931v1.90","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.123"},{"key":"2026042808350724000_2026.04.21.719931v1.91","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.07.005"},{"key":"2026042808350724000_2026.04.21.719931v1.92","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-3122"},{"key":"2026042808350724000_2026.04.21.719931v1.93","doi-asserted-by":"publisher","DOI":"10.1021\/bi0103516"},{"key":"2026042808350724000_2026.04.21.719931v1.94","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602262200"},{"key":"2026042808350724000_2026.04.21.719931v1.95","doi-asserted-by":"publisher","DOI":"10.1021\/bi201213w"},{"key":"2026042808350724000_2026.04.21.719931v1.96","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2018.07.016"},{"key":"2026042808350724000_2026.04.21.719931v1.97","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.42.25723"},{"key":"2026042808350724000_2026.04.21.719931v1.98","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0372OC"},{"key":"2026042808350724000_2026.04.21.719931v1.99","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35862-0"},{"key":"2026042808350724000_2026.04.21.719931v1.100","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421190112"},{"key":"2026042808350724000_2026.04.21.719931v1.101","doi-asserted-by":"publisher","DOI":"10.1513\/pats.2306011"},{"key":"2026042808350724000_2026.04.21.719931v1.102","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.031538898"},{"key":"2026042808350724000_2026.04.21.719931v1.103","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312871200"},{"key":"2026042808350724000_2026.04.21.719931v1.104","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-007-9437-2"},{"key":"2026042808350724000_2026.04.21.719931v1.105","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.148098"},{"key":"2026042808350724000_2026.04.21.719931v1.106","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.337865"},{"key":"2026042808350724000_2026.04.21.719931v1.107","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E22-02-0045"},{"key":"2026042808350724000_2026.04.21.719931v1.108","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518966112"},{"key":"2026042808350724000_2026.04.21.719931v1.109","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2.5.719"},{"key":"2026042808350724000_2026.04.21.719931v1.110","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.05.016"},{"key":"2026042808350724000_2026.04.21.719931v1.111","doi-asserted-by":"publisher","DOI":"10.3390\/genes10020172"},{"key":"2026042808350724000_2026.04.21.719931v1.112","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12102922"},{"key":"2026042808350724000_2026.04.21.719931v1.113","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2020.12.042"},{"key":"2026042808350724000_2026.04.21.719931v1.114","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg6593"},{"key":"2026042808350724000_2026.04.21.719931v1.115","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102605"},{"key":"2026042808350724000_2026.04.21.719931v1.116","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2012.01.002"},{"key":"2026042808350724000_2026.04.21.719931v1.117","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.713542"},{"key":"2026042808350724000_2026.04.21.719931v1.118","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000031107"},{"key":"2026042808350724000_2026.04.21.719931v1.119","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2025.101202"},{"key":"2026042808350724000_2026.04.21.719931v1.120","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081101"},{"key":"2026042808350724000_2026.04.21.719931v1.121","doi-asserted-by":"publisher","DOI":"10.1002\/evl3.273"},{"key":"2026042808350724000_2026.04.21.719931v1.122","doi-asserted-by":"publisher","DOI":"10.1186\/s41021-023-00283-4"},{"key":"2026042808350724000_2026.04.21.719931v1.123","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49771"},{"key":"2026042808350724000_2026.04.21.719931v1.124","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0202OC"},{"key":"2026042808350724000_2026.04.21.719931v1.125","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0338ED"},{"key":"2026042808350724000_2026.04.21.719931v1.126","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-024400"},{"key":"2026042808350724000_2026.04.21.719931v1.127","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-192377"},{"key":"2026042808350724000_2026.04.21.719931v1.128","doi-asserted-by":"publisher","DOI":"10.1159\/000453162"},{"key":"2026042808350724000_2026.04.21.719931v1.129","doi-asserted-by":"publisher","DOI":"10.1136\/thorax-2022-219668"},{"key":"2026042808350724000_2026.04.21.719931v1.130","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201608-649OC"},{"key":"2026042808350724000_2026.04.21.719931v1.131","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-02025-6"},{"key":"2026042808350724000_2026.04.21.719931v1.132","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-025-03662-z"},{"key":"2026042808350724000_2026.04.21.719931v1.133","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.104972"},{"key":"2026042808350724000_2026.04.21.719931v1.134","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3277"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.21.719931","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:35:17Z","timestamp":1777390517000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.21.719931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":134,"URL":"https:\/\/doi.org\/10.64898\/2026.04.21.719931","relation":{},"subject":[],"published":{"date-parts":[[2026,4,24]]},"subtype":"preprint"}}