{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:01:24Z","timestamp":1789984884583,"version":"4.0.1"},"reference-count":88,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 ES031253"],"award-info":[{"award-number":["R01 ES031253"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES031253-04S1"],"award-info":[{"award-number":["ES031253-04S1"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES034628"],"award-info":[{"award-number":["ES034628"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Community Foundation for the Ohio Valley Whipkey Charitable Funds","id":[{"id":"https:\/\/ror.org\/045p1r112","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/045p1r112","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Extreme heat events are increasing in frequency, duration, and severity, often with higher air pollution (AP) levels. The biological mechanisms underlying combined heat and AP exposures and the role of NLRX1 in pulmonary and cardiac dysfunction remain largely undefined. Nlrx1+\/+ and Nlrx1\u2212\/\u2212 female mice were exposed to filtered air\/CTR, HT (36 \u00b0C), ultrafine carbon black (UfCB) + ozone (O3) (CB 2.5 mg\/m3 + O3 1 ppm), and HT + UfCB + O3 for 3 h. Pulmonary inflammation was evaluated by bronchoalveolar lavage, while cardiac function and strain were evaluated using Doppler echocardiography. Mitochondrial function was assessed through coupling assay and ETC complex activity measurements. Both at 2 and 24 h, Nlrx1\u2212\/\u2212 mice showed no adaptive physiological cardiac responses and demonstrated impaired mitochondrial function after heat-alone exposure. UfCB + O3-alone exposure induced a decrease in stroke volume and cardiac output and a decrease in cardiac mitochondrial complex III\u2013V activities in both genotypes. Combined HT + UfCB + O3 resulted in a greater reduction in ejection fraction percentage and fractional shortening percentage, greater pulmonary neutrophilia, and a reduction in complex III\u2013V activities at 24 h post-exposure in Nlrx1\u2212\/\u2212 mice compared to Nlrx1+\/+ mice. Moreover, Nlrx1\u2212\/\u2212 mice demonstrated a greater decrease in longitudinal and circumferential strain, indicating dyssynchronous contraction throughout the heart layers and mid-cavity segments. Collectively, our findings indicate that NLRX1 deficiency alters the acute physiological cardiopulmonary responses to HT and UfCB + O3.<\/jats:p>","DOI":"10.3390\/cells15181699","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heart Function Changes During Environmentally Relevant Combined Exposure to Heat, Ultrafine Carbon Black, and Ozone: Role of NOD-like Receptor X1"],"prefix":"10.3390","volume":"15","author":[{"given":"Chiara","family":"Monge","sequence":"first","affiliation":[{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-0200","authenticated-orcid":false,"given":"William Travis","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Razazan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9751-538X","authenticated-orcid":false,"given":"Murugesan","family":"Velayutham","sequence":"additional","affiliation":[{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Meadows","sequence":"additional","affiliation":[{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Eminhizer","sequence":"additional","affiliation":[{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hollander","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0339-6226","authenticated-orcid":false,"given":"Salik","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Department of Microbiology, Immunology and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1183\/09059180.00001714","article-title":"Climate change and respiratory diseases","volume":"23","author":"Cecchi","year":"2014","journal-title":"Eur. 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