{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:21:32Z","timestamp":1787826092424,"version":"build-2784847793"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health R01","doi-asserted-by":"publisher","award":["HL142997"],"award-info":[{"award-number":["HL142997"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. The airway is the primary target in severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks of exposure. The viral factors that contribute to cell death and lung injury remain incompletely understood. Thus, this study investigated the role of open reading frame 7b (Orf7b), an accessory protein of the virus, in causing lung injury. In screening viral proteins, we identified Orf7b as one of the major viral factors that mediates lung epithelial cell death. Overexpression of Orf7b leads to apoptosis and ferroptosis in lung epithelial cells, and inhibitors of apoptosis and ferroptosis ablate Orf7b-induced cell death. Orf7b upregulates the transcription regulator, c-Myc, which is integral in the activation of lung cell death pathways. Depletion of c-Myc alleviates both apoptotic and ferroptotic cell deaths and lung injury in mouse models. Our study suggests a major role of Orf7b in the cell death and lung injury attributable to COVID-19 exposure, supporting it as a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms25021157","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T03:50:56Z","timestamp":1705549856000},"page":"1157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis"],"prefix":"10.3390","volume":"25","author":[{"given":"Rushikesh","family":"Deshpande","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiao","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2641-8152","authenticated-orcid":false,"given":"Kristen V.","family":"Fanning","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Clemens","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-4607","authenticated-orcid":false,"given":"Toru","family":"Nyunoya","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthony","family":"Deslouches","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Barchowsky","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"McDyer","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1355-4726","authenticated-orcid":false,"given":"Chunbin","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2023). COVID Data Tracker."},{"key":"ref_2","first-page":"e7423","article-title":"Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update","volume":"12","author":"Pal","year":"2020","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s10930-020-09901-4","article-title":"The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2 or n-COV19), the Cause of COVID-19","volume":"39","author":"Yoshimoto","year":"2020","journal-title":"Protein J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3390\/jor1040021","article-title":"Programmed Cell Death in SARS-CoV-2 Infection: A Short Review","volume":"1","author":"Deshpande","year":"2021","journal-title":"J. Respir."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"m1470","DOI":"10.1136\/bmj.m1470","article-title":"Clinical features of COVID-19","volume":"369","author":"Vetter","year":"2020","journal-title":"BMJ"},{"key":"ref_6","first-page":"13","article-title":"Clinical features of COVID-19 and SARS epidemics. A literature review","volume":"62","author":"Zizza","year":"2021","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.freeradbiomed.2017.04.024","article-title":"Iron and thiol redox signaling in cancer: An exquisite balance to escape ferroptosis","volume":"108","author":"Toyokuni","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1021\/acscentsci.7b00589","article-title":"Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis","volume":"4","author":"Shah","year":"2018","journal-title":"ACS Cent. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fratta Pasini, A.M., Stranieri, C., Girelli, D., Busti, F., and Cominacini, L. (2021). Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?. Antioxidants, 10.","DOI":"10.3390\/antiox10111677"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yang, R., Zhao, Q., Rao, J., Zeng, F., Yuan, S., Ji, M., Sun, X., Li, J., Yang, J., and Cui, J. (2021). SARS-CoV-2 Accessory Protein ORF7b Mediates Tumor Necrosis Factor-\u03b1-Induced Apoptosis in Cells. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.654709"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11054","DOI":"10.1128\/JVI.01266-07","article-title":"Severe acute respiratory syndrome coronavirus gene 7 products contribute to virus-induced apoptosis","volume":"81","author":"Schaecher","year":"2007","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41467-021-20904-2","article-title":"NUPR1 is a critical repressor of ferroptosis","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41420-021-00662-2","article-title":"NUPR1 inhibitor ZZW-115 induces ferroptosis in a mitochondria-dependent manner","volume":"7","author":"Huang","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0014-5793(95)01116-V","article-title":"An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytic THP.1 cells","volume":"374","author":"Zhu","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/6514","article-title":"Neuroprotection by a caspase inhibitor in acute bacterial meningitis","volume":"5","author":"Braun","year":"1999","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Miotto, G., Rossetto, M., Di Paolo, M.L., Orian, L., Venerando, R., Roveri, A., Vu\u010dkovi\u0107, A.-M., Travain, V.B., Zaccarin, M., and Zennaro, L. (2020). Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol., 28.","DOI":"10.1016\/j.redox.2019.101328"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Schneider","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1038\/onc.2008.312","article-title":"Apoptotic signaling by c-MYC","volume":"27","author":"Hoffman","year":"2008","journal-title":"Oncogene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.chembiol.2020.03.007","article-title":"The Chemical Biology of Ferroptosis in the Central Nervous System","volume":"27","author":"Ratan","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.3390\/cells11244127","article-title":"C-MYC Inhibited Ferroptosis and Promoted Immune Evasion in Ovarian Cancer Cells through NCOA4 Mediated Ferritin Autophagy","volume":"11","author":"Jin","year":"2022","journal-title":"Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.7150\/thno.19988","article-title":"EGLN1\/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes","volume":"7","author":"Jiang","year":"2017","journal-title":"Theranostics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s43018-022-00355-4","article-title":"MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis","volume":"3","author":"Alborzinia","year":"2022","journal-title":"Nat. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101","DOI":"10.21315\/mjms2017.24.5.11","article-title":"Sample Size Calculation in Animal Studies Using Resource Equation Approach","volume":"24","author":"Arifin","year":"2017","journal-title":"Malays. J. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/ilar.47.1.5","article-title":"Design and statistical methods in studies using animal models of development","volume":"47","author":"Festing","year":"2006","journal-title":"Ilar J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1152\/physiol.00033.2021","article-title":"Mechanisms of Lung Injury Induced by SARS-CoV-2 Infection","volume":"37","author":"Upadhya","year":"2022","journal-title":"Physiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1038\/s41379-020-00661-1","article-title":"COVID-19 pulmonary pathology: A multi-institutional autopsy cohort from Italy and New York City","volume":"33","author":"Borczuk","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.3201\/eid2609.202095","article-title":"COVID-19 Pathology Working Group. Pathology and rathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United States","volume":"26","author":"Martines","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/s41379-020-0536-x","article-title":"Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies","volume":"33","author":"Tian","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_32","first-page":"1","article-title":"In silico proteome analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)","volume":"2","author":"Baruah","year":"2021","journal-title":"J. Nanotechnol. Nanomater."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shemesh, M., Aktepe, T.E., Deerain, J.M., McAuley, J.L., Audsley, M.D., David, C.T., Purcell, D.F.J., Urin, V., Hartmann, R., and Moseley, G.W. (2021). SARS-CoV-2 suppresses IFN\u03b2 production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon. PLoS Pathog., 17, Erratum in PLoS Pathog. 2021, 17, e1010146.","DOI":"10.1371\/journal.ppat.1010146"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105444","DOI":"10.1016\/j.isci.2022.105444","article-title":"Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b","volume":"25","author":"Redondo","year":"2022","journal-title":"iScience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0040221","DOI":"10.1128\/JVI.00402-21","article-title":"Contribution of SARS-CoV-2 Accessory Proteins to Viral Pathogenicity in K18 Human ACE2 Transgenic Mice","volume":"95","author":"Silvas","year":"2021","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41423-020-0485-9","article-title":"The ORF3a protein of SARS-CoV-2 induces apoptosis in cells","volume":"17","author":"Ren","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lee, J.G., Huang, W., Lee, H., van de Leemput, J., Kane, M.A., and Han, Z. (2021). Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor. Cell Biosci., 11.","DOI":"10.1186\/s13578-021-00568-7"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"728896","DOI":"10.3389\/fimmu.2021.728896","article-title":"SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril)","volume":"12","author":"Barhoumi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1038\/s41418-022-00928-x","article-title":"SARS-CoV-2 membrane protein causes the mitochondrial apoptosis and pulmonary edema via targeting BOK","volume":"29","author":"Yang","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, L., Du, J., Yang, S., Zheng, B., Shen, J., Huang, J., Cao, L., Huang, S., Liu, X., and Guo, L. (2023). SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. Redox Biol., 63.","DOI":"10.1016\/j.redox.2023.102752"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1086\/519166","article-title":"Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis","volume":"196","author":"Chen","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"198350","DOI":"10.1016\/j.virusres.2021.198350","article-title":"The ORF8 protein of SARS-CoV-2 induced endoplasmic reticulum stress and mediated immune evasion by antagonizing production of interferon beta","volume":"296","author":"Rashid","year":"2021","journal-title":"Virus Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1164\/rccm.202111-2493OC","article-title":"CD4+ T-Cell Dysfunction in Severe COVID-19 Disease Is Tumor Necrosis Factor-\u03b1\/Tumor Necrosis Factor Receptor 1-Dependent","volume":"205","author":"Popescu","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8541","DOI":"10.1128\/MCB.24.19.8541-8555.2004","article-title":"Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity","volume":"24","author":"Ricci","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5442","DOI":"10.1002\/j.1460-2075.1994.tb06879.x","article-title":"c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha","volume":"13","author":"Klefstrom","year":"1994","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1161\/CIRCRESAHA.122.320951","article-title":"Ferroptosis of Pacemaker Cells in COVID-19","volume":"130","author":"Nishiga","year":"2022","journal-title":"Circ. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, B., Shen, W.B., Yang, P., and Turan, S. (2022). SARS-CoV-2 infection induces activation of ferroptosis in human placenta. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1022747"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3390\/antiox12020326","article-title":"COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells","volume":"12","author":"Jankauskas","year":"2023","journal-title":"Antioxidants"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","article-title":"MYC on the path to cancer","volume":"149","author":"Dang","year":"2012","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1126\/science.283.5402.676","article-title":"Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC","volume":"283","author":"Wu","year":"1999","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7423","DOI":"10.1128\/MCB.25.17.7423-7431.2005","article-title":"p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest","volume":"25","author":"Ho","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0005822","DOI":"10.1128\/msystems.00058-22","article-title":"Stability of SARS-CoV-2-Encoded Proteins and Their Antibody Levels Correlate with Interleukin 6 in COVID-19 Patients","volume":"7","author":"Li","year":"2022","journal-title":"mSystems"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"24301","DOI":"10.18632\/aging.202210","article-title":"Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6\/AKT signaling","volume":"12","author":"Li","year":"2020","journal-title":"Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1002\/cpns.103","article-title":"AAV Production Everywhere: A Simple, Fast, and Reliable Protocol for In-house AAV Vector Production Based on Chloroform Extraction","volume":"93","author":"Negrini","year":"2020","journal-title":"Curr. Protoc. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:49:17Z","timestamp":1760104157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,18]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25021157"],"URL":"https:\/\/doi.org\/10.3390\/ijms25021157","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,18]]}}}