{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:49:01Z","timestamp":1782809341284,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deep Blue Advancing Talent (Zifei Yin) of Naval Medical University"},{"name":"National Administration of Traditional Chinese Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cold seawater immersion is a critical lethal risk in maritime accidents and military operations, frequently inducing fatal myocardial dysfunction. However, the mechanisms underlying this seawater immersion hypothermia-induced cardiac injury remain poorly defined. This study aimed to elucidate the pathological progression and underlying mechanisms of myocardial injury induced by cold seawater immersion. A male SD rat model was immersed in 15 \u00b0C seawater for 2 h. Echocardiography, transmission electron microscopy, transcriptomics, and Western blot were performed to assess cardiac function, mitochondrial ultrastructure, and molecular mechanisms. Cold stress triggered progressive bradycardia (~480 to ~100 bpm) with initial Frank\u2013Starling compensation, followed by decompensation with reduced cardiac output and impaired diastolic function. Mitochondrial ultrastructural damage preceded histological lesions and was accompanied by elevated cardiac injury markers (cTnT, CK-MB, BNP). Cardiac tissue exhibited upregulated TNF-\u03b1, IL-1\u03b2, and IL-6, while transcriptomic analysis revealed enrichment of inflammatory pathways (TNF, NF-\u03baB) and coordinated upregulation of pattern recognition receptors including scavenger receptor, Toll-like receptor, and NOD-like receptor families. The Western blot confirmed NF-\u03baB activation, NLRP3 inflammasome assembly, and the N-terminal fragment of gasdermin D (GSDMD-NT) accumulation, indicating pyroptotic cell death. These findings demonstrate that cold seawater stress disrupts mitochondrial homeostasis and activates the NF-\u03baB\/NLRP3\/pyroptosis cascade, contributing to inflammatory cardiomyocyte death and cardiac decompensation. This mechanistic insight may inform therapeutic strategies for seawater immersion hypothermia.<\/jats:p>","DOI":"10.3390\/ijms27135890","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"5890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seawater Immersion Hypothermia Triggers Cardiac Pyroptosis via the NF-\u03baB\/NLRP3 Inflammasome Axis: A Mechanistic Study in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0643-1974","authenticated-orcid":false,"given":"Huifang","family":"Deng","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyue","family":"Sun","sequence":"additional","affiliation":[{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Ben","sequence":"additional","affiliation":[{"name":"Graduate School, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate School, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wumu","family":"Xu","sequence":"additional","affiliation":[{"name":"Graduate School, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Basic Medicine College, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"Changhai Hospital, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanrong","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyang","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-4510","authenticated-orcid":false,"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifei","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","unstructured":"International Institute of Marine Surveying (IIMS) (2026, March 10). Annual Overview of Marine Casualties and Incidents 2025 Report Published by EMSA. Available online: https:\/\/www.iims.org.uk\/annual-overview-of-marine-casualties-and-incidents-2025-report-published-by-emsa\/."},{"key":"ref_2","unstructured":"Marine Accident Investigation Branch (2026, April 24). Planning and Preparation Vital to Reduce Man Overboard Fatalities, Available online: https:\/\/www.gov.uk\/government\/news\/planning-and-preparation-vital-to-reduce-man-overboard-fatalities."},{"key":"ref_3","unstructured":"National Center for Cold Water Safety (2026, April 24). Why Cold Water Is Dangerous. Available online: https:\/\/www.coldwatersafety.org\/the-danger."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Peter, S., Michaelis, A., Wagner, R., Marshall, R.P., Bovet, M., Weickmann, J., Weidenbach, M., D\u00e4hnert, I., and Paech, C. (2026). Cold shock response in healthy children: Reassessment and first comparison between cold and warm water immersion. Front. Sports Act. Living, 7.","DOI":"10.3389\/fspor.2025.1610144"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2236777","DOI":"10.1080\/22423982.2023.2236777","article-title":"Prevalence of hypothermia and critical hand temperatures during military cold water immersion training","volume":"82","author":"Jones","year":"2023","journal-title":"Int. J. Circumpolar Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ssci.2017.09.009","article-title":"Factors associated with crewmember survival of commercial fishing vessel sinkings in Alaska","volume":"101","author":"Lucas","year":"2017","journal-title":"Saf. Sci."},{"key":"ref_7","first-page":"S41","article-title":"Injury trends aboard US Navy vessels: A 50-year analysis of mishaps at sea","volume":"95","author":"Benham","year":"2023","journal-title":"J. Trauma. Acute Care Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"042009","DOI":"10.1088\/2516-1091\/ae0c4b","article-title":"Physiology and enabling technologies for quantitative assessment of survivability during cold water immersion and rewarming: A review","volume":"7","author":"Bouzid","year":"2025","journal-title":"Prog. Biomed. Eng."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.resuscitation.2021.08.016","article-title":"Hypothermic Cardiac Arrest\u2014Retrospective cohort study from the International Hypothermia Registry","volume":"167","author":"Walpoth","year":"2021","journal-title":"Resuscitation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1130","DOI":"10.1161\/CIR.0000000000001419","article-title":"Nonoptimal Temperature and Cardiovascular Health: A Scientific Statement From the American Heart Association","volume":"153","author":"Hanneman","year":"2026","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1093\/cvr\/cvz309","article-title":"Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology","volume":"116","author":"Dietrichs","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bjertn\u00e6s, L.J., N\u00e6sheim, T.O., Reierth, E., Suborov, E.V., Kirov, M.Y., Lebedinskii, K.M., and Tveita, T. (2022). Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update. Front. Med., 9.","DOI":"10.3389\/fmed.2022.824395"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110923","DOI":"10.1016\/j.resuscitation.2025.110923","article-title":"Hypoxemia in hypothermic cardiac arrest: Why one number should not decide a life","volume":"218","author":"Varon","year":"2025","journal-title":"Resuscitation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110917","DOI":"10.1016\/j.resuscitation.2025.110917","article-title":"Oxygenation metrics have limited prognostic value in non-asphyxial hypothermic cardiac arrest","volume":"218","author":"Mendrala","year":"2025","journal-title":"Resuscitation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s12012-023-09823-4","article-title":"Heavy Metal Scavenger Metallothionein Rescues Against Cold Stress-Evoked Myocardial Contractile Anomalies Through Regulation of Mitophagy","volume":"24","author":"Pei","year":"2024","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157997","DOI":"10.1016\/j.phymed.2026.157997","article-title":"Ginsenoside Rg2 ameliorates acute cold exposure\/rewarming-induced myocardial injury via modulating HMGB1\/TLR4\/NF-\u03baB and PGC-1\u03b1 signaling pathways: Role of SIRT1","volume":"153","author":"Zuo","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kong, X., Liu, H., He, X., Sun, Y., and Ge, W. (2020). Unraveling the Mystery of Cold Stress-Induced Myocardial Injury. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.580811"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e33022","DOI":"10.1016\/j.heliyon.2024.e33022","article-title":"Computational insights into survival durations and prehospital interventions in accidental cold-water immersion: A comprehensive analysis of fresh and saltwater temperatures","volume":"10","author":"Junaid","year":"2024","journal-title":"Heliyon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103984","DOI":"10.1016\/j.psj.2024.103984","article-title":"Intermittent and mild cold stimulation enhances immune function of broilers via co-regulation of CIRP and TRPM8 on NF-\u03baB and MAPK signaling pathways","volume":"103","author":"Xing","year":"2024","journal-title":"Poult. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.4142\/jvs.22185","article-title":"Chronic cold stress-induced myocardial injury: Effects on oxidative stress, inflammation and pyroptosis","volume":"24","author":"Lv","year":"2023","journal-title":"J. Vet. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cain, T., Brinsley, J., Bennett, H., Nelson, M., Maher, C., and Singh, B. (2025). Effects of cold-water immersion on health and wellbeing: A systematic review and meta-analysis. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0317615"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1038\/s12276-023-01133-7","article-title":"Processing stimulus dynamics by the NF-\u03baB network in single cells","volume":"55","author":"Son","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2023.09.007","article-title":"Mechanisms of NLRP3 inflammasome activation and the development of peptide inhibitors","volume":"74","author":"Ye","year":"2023","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41392-024-01958-2","article-title":"Pyroptosis in health and disease: Mechanisms, regulation and clinical perspective","volume":"9","author":"Liu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, Y., Xue, N., Zhang, B., Lv, H., and Li, S. (2022). Cold Stress Induced Liver Injury of Mice through Activated NLRP3\/Caspase-1\/GSDMD Pyroptosis Signaling Pathway. Biomolecules, 12.","DOI":"10.3390\/biom12070927"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Teng, T., Yang, H., Xu, T., Sun, G., Song, X., Bai, G., and Shi, B. (2022). Activation of Inflammatory Networks in the Lungs Caused by Chronic Cold Stress Is Moderately Attenuated by Glucose Supplementation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810697"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/ther.2021.0033","article-title":"Water Rewarming After Seawater Hypothermia Mitigates IL-1\u03b2 in Both Intestinal Tissue and Blood","volume":"13","author":"Li","year":"2022","journal-title":"Ther. Hypothermia Temp. Manag."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1159\/000533602","article-title":"Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity","volume":"15","author":"Lyu","year":"2023","journal-title":"J. Innate Immun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yamada, K.P., Kariya, T., Aikawa, T., and Ishikawa, K. (2021). Effects of Therapeutic Hypothermia on Normal and Ischemic Heart. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.642843"},{"key":"ref_30","first-page":"53","article-title":"The Heart is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect","volume":"87","author":"Banyasz","year":"2024","journal-title":"Annu. Rev. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resuscitation.2019.06.276","article-title":"Impact of hypothermia on cardiac performance during targeted temperature management after cardiac arrest","volume":"142","author":"Chen","year":"2019","journal-title":"Resuscitation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra2312086","article-title":"Cardiogenic Shock","volume":"394","author":"Thiele","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e184134","DOI":"10.1172\/JCI184134","article-title":"Mechanisms of postischemic cardiac death and protection following myocardial injury","volume":"135","author":"Mastoor","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1089\/ars.2022.0167","article-title":"Role of Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1","volume":"41","author":"Liu","year":"2024","journal-title":"Antioxid. Redox Signal."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bader, W., Steinacher, C., Fischer, H.T., Glueckert, R., Schmutzhard, J., and Schrott-Fischer, A. (2023). Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108850"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41577-024-01027-3","article-title":"DAMP sensing and sterile inflammation: Intracellular, intercellular and inter-organ pathways","volume":"24","author":"Huang","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s10495-021-01663-3","article-title":"Release mechanisms of major DAMPs","volume":"26","author":"Murao","year":"2021","journal-title":"Apoptosis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41577-022-00760-x","article-title":"Mitochondrial control of inflammation","volume":"23","author":"Marchi","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20368","DOI":"10.1038\/s41598-024-71473-5","article-title":"A composite patch loaded with 2-Deoxy Glucose facilitates cardiac recovery after myocardial infarction via attenuating local inflammatory response","volume":"14","author":"Xiao","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-025-02264-1","article-title":"Pattern recognition receptors: Function, regulation and therapeutic potential","volume":"10","author":"Chen","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1055\/s-0041-1733876","article-title":"Scavenger Receptors: Novel Roles in the Pathogenesis of Liver Inflammation and Cancer","volume":"42","author":"Patten","year":"2021","journal-title":"Semin. Liver Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s40364-022-00436-7","article-title":"Targeting toll-like receptor 7\/8 for immunotherapy: Recent advances and prospectives","volume":"10","author":"Sun","year":"2022","journal-title":"Biomark. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/intimm\/dxaf010","article-title":"Zoledronic acid attenuates ischemic brain injury by promoting ETS2 and MSR1 expression","volume":"37","author":"Otani","year":"2025","journal-title":"Int. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sheng, W., Ji, G., and Zhang, L. (2022). Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1050984"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41569-023-00946-3","article-title":"The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases","volume":"21","author":"Toldo","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41392-021-00507-5","article-title":"Pyroptosis: Mechanisms and diseases","volume":"6","author":"Yu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/s12964-023-01359-y","article-title":"Simvastatin induces pyroptosis via ROS\/caspase-1\/GSDMD pathway in colon cancer","volume":"21","author":"Xie","year":"2023","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"102305","DOI":"10.1016\/j.redox.2022.102305","article-title":"XBP1 deficiency promotes hepatocyte pyroptosis by impairing mitophagy to activate mtDNA-cGAS-STING signaling in macrophages during acute liver injury","volume":"52","author":"Liu","year":"2022","journal-title":"Redox Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.immuni.2024.10.012","article-title":"Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation","volume":"58","author":"Saller","year":"2025","journal-title":"Immunity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"108671","DOI":"10.1016\/j.intimp.2022.108671","article-title":"SIRT1 alleviates IL-1\u03b2 induced nucleus pulposus cells pyroptosis via mitophagy in intervertebral disc degeneration","volume":"107","author":"Ma","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jacbts.2022.08.003","article-title":"Inflammatory Macrophage Interleukin-1\u03b2 Mediates High-Fat Diet-Induced Heart Failure with Preserved Ejection Fraction","volume":"8","author":"Liu","year":"2023","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1093\/eurheartj\/ehaf024","article-title":"Atrial cardiomyocyte-restricted cleavage of gasdermin D promotes atrial arrhythmogenesis","volume":"46","author":"Yuan","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.tcb.2023.02.007","article-title":"Gasdermins gone wild: New roles for GSDMs in regulating cellular homeostasis","volume":"33","author":"Weindel","year":"2023","journal-title":"Trends Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:40:35Z","timestamp":1782808835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":54,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135890"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135890","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}