{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:18:37Z","timestamp":1765995517196,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012453","name":"CARS","doi-asserted-by":"publisher","award":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"],"award-info":[{"award-number":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"]}],"id":[{"id":"10.13039\/501100012453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biological Breeding-Major Projects","award":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"],"award-info":[{"award-number":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"],"award-info":[{"award-number":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Public-Interest Scientific Institution Basal Research Fund","award":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"],"award-info":[{"award-number":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"]}]},{"name":"Central Public-Interest Scientific Institution Basal Research Fund","award":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"],"award-info":[{"award-number":["CARS-45","2023ZD04054","2022YFD2400100","2023TD36","YFI202407"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Silver carp is a critically significant species in freshwater aquaculture in China, characterized by its limited tolerance to hypoxia. In this study, a significant SNP locus at Chr8: 29647765 (T\/C) associated with hypoxia tolerance traits was identified in Changfeng silver carp, and the homozygotic CC genotype exhibited higher hypoxic tolerance than the homozygotic TT and heterozygotic TC genotypes. Under hypoxic conditions, the hemoglobin concentration increased, with the CC genotype demonstrating a significantly higher level compared with the TT genotype; the activities of antioxidant enzymes including catalase and superoxide dismutase were significantly higher in the CC genotype than in the other genotypes; the area of the gill lamellae was significantly smaller in the CC genotype than in the TT and TC genotypes; and the number of apoptotic cells in the brain was significantly lower in the CC genotype than in the TT and TC genotypes. Sequence analysis showed that this SNP was located in the promoter region of the cathepsin C (CTSC) gene. The expression levels of the CTSC gene were analyzed across the three genotypes, revealing that the CC genotype exhibited significantly lower expression compared with the TT and TC genotypes under hypoxia. This finding suggests that the SNP associated with the CC genotype leads to reduced CTSC expression, which may facilitate better physiological adaptation to hypoxia. Analysis of the promoter region of CTSC found a unique predicted hypoxia-inducible factor 1-alpha (HIF-1\u03b1) binding site (CGTG) in the T genotype, implying that the differential expression of CTSC among the three genotypes under hypoxic stress may be regulated by HIF-1\u03b1, a transcription factor integral to hypoxia adaptation, thereby affecting hypoxia tolerance, which further affects the immune response of the Changfeng silver carp in response to the hypoxic environment. Although SNPs represent significant genetic determinants, their phenotypic effects are predominantly mediated through complex interactions within gene regulatory networks and environmental influences. This study identified an effective SNP site in Changfeng silver carp, providing valuable guidance for future selective breeding and the development of new hypoxia-tolerant varieties.<\/jats:p>","DOI":"10.3390\/ani15040532","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T05:10:22Z","timestamp":1739423422000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A 5\u2032 Promoter Region SNP in CTSC Leads to Increased Hypoxia Tolerance in Changfeng Silver Carp (Hypophthalmichthys molitrix)"],"prefix":"10.3390","volume":"15","author":[{"given":"Nannan","family":"Feng","sequence":"first","affiliation":[{"name":"Laboratory of Zoological Systematics and Application of Hebei Province, College of Life Sciences, Hebei University, Baoding 071002, China"},{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-3270","authenticated-orcid":false,"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Sha","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangzhong","family":"Luo","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiwei","family":"Zou","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5063-339X","authenticated-orcid":false,"given":"Jiquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Zoological Systematics and Application of Hebei Province, College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-5006","authenticated-orcid":false,"given":"Hongwei","family":"Liang","sequence":"additional","affiliation":[{"name":"Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China"},{"name":"Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.aquaculture.2016.05.008","article-title":"Aerobic scope and oxygen regulation of New Zealand geoduck (Panopea zelandica) in response to progressive hypoxia","volume":"463","author":"Le","year":"2016","journal-title":"Aquaculture"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.gene.2007.03.009","article-title":"Molecular cloning, characterization and expression of two hypoxia-inducible factor alpha subunits, HIF-1\u03b1 and HIF-2\u03b1, in a hypoxia-tolerant marine teleost, Atlantic croaker (Micropogonias undulatus)","volume":"396","author":"Rahman","year":"2007","journal-title":"Gene"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.aquaeng.2006.02.004","article-title":"Behavioral responses of tilapia (Oreochromis niloticus) to acute fluctuations in dissolved oxygen levels as monitored by computer vision","volume":"35","author":"Xu","year":"2006","journal-title":"Aquac. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Aksakal, E., and Ekinci, D. (2021). Effects of hypoxia and hyperoxia on growth parameters and transcription levels of growth, immune system and stress related genes in rainbow trout. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol., 262.","DOI":"10.1016\/j.cbpa.2021.111060"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1007\/s10499-015-9882-y","article-title":"Effects of dissolved oxygen and fish size on Nile tilapia, Oreochromis niloticus (L.): Growth performance, whole-body composition, and innate immunity","volume":"23","author":"Hagras","year":"2015","journal-title":"Aquac. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gene.2017.10.002","article-title":"Acute hypoxia stress induced abundant differential expression genes and alternative splicing events in heart of tilapia","volume":"639","author":"Xia","year":"2018","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1095-8649.1990.tb05610.x","article-title":"Haematological response to reduced oxygen-carrying capacity, increased temperature and hypoxia in goldfish, Carassius auratus L","volume":"36","author":"Murad","year":"2010","journal-title":"J. Fish Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1086\/673180","article-title":"Interspecific differences in hypoxia-induced gill remodeling in carp","volume":"86","author":"Dhillon","year":"2013","journal-title":"Physiol. Biochem. Zool."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sollid, J. (2003). Hypoxia induces adaptive and reversible gross morphological changes in crucian carp gills. J. Exp. Biol., 206.","DOI":"10.1242\/jeb.00594"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Xu, X.-N., Chen, S.-L., Jiang, Z.-X., Nissa, M.u., and Zou, S.-M. (2022). Gill remodeling increases the respiratory surface area of grass carp (Ctenopharyngodon idella) under hypoxic stress. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol., 272.","DOI":"10.1016\/j.cbpa.2022.111278"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1080\/19425120.2011.601982","article-title":"Oxygen Consumption of the Prawn Macrobrachium americanum over the Temperature Range of its Native Environment and in Relation to its Weight","volume":"73","year":"2011","journal-title":"N. Am. J. Aquac."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104160","DOI":"10.1016\/j.dci.2021.104160","article-title":"Expression and functional analysis of the BCL2-Associated agonist of cell death (BAD) gene in grass carp (Ctenopharyngodon idella) during bacterial infection","volume":"123","author":"Lu","year":"2021","journal-title":"Dev. Comp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/S0140-6736(84)91886-5","article-title":"Lipid Peroxidation, Oxygen Radicals, Cell Damage, and Antioxidant Therapy","volume":"323","author":"Halliwell","year":"1984","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.fsi.2010.11.003","article-title":"Molecular cloning and differential expression patterns of copper\/zinc superoxide dismutase and manganese superoxide dismutase in Hypophthalmichthys molitrix","volume":"30","author":"Zhang","year":"2011","journal-title":"Fish Shellfish Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.molp.2017.06.008","article-title":"Crop Breeding Chips and Genotyping Platforms: Progress, Challenges, and Perspectives","volume":"10","author":"Rasheed","year":"2017","journal-title":"Mol. Plant"},{"key":"ref_16","first-page":"307","article-title":"SNPs Detection of GHRL Gene and Its Association with Growth Traits of Chinese Soft-Shell Turtle (Pelodiscus Sinensis)","volume":"42","author":"Li","year":"2018","journal-title":"Acta Hydrobiol. Sin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"737098","DOI":"10.1016\/j.aquaculture.2021.737098","article-title":"Genome-wide association study reveals multiple novel SNPs and putative candidate genes associated with low oxygen tolerance in golden pompano Trachinotus ovatus (Linnaeus 1758)","volume":"544","author":"San","year":"2021","journal-title":"Aquaculture"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/jfb.14253","article-title":"Native bighead carp Hypophthalmichthys nobilis and silver carp Hypophthalmichthys molitrix populations in the Pearl River are threatened by Yangtze River introductions as revealed by mitochondrial DNA","volume":"96","author":"Li","year":"2020","journal-title":"J. Fish Biol."},{"key":"ref_19","unstructured":"(2024). China Fishery Statistical Yearbook, China Agriculture Press."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, M., Ling, C., Sha, H., Zou, G., and Liang, H. (2022). Molecular Characterization and Response of Prolyl Hydroxylase Domain (PHD) Genes to Hypoxia Stress in Hypophthalmichthys molitrix. Animals, 12.","DOI":"10.3390\/ani12020131"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.aquaculture.2014.11.007","article-title":"A consecutive self-proliferate silver carp (Hypophthalmichthys molitrix) variety created through artificial meiotic gynogenesis","volume":"437","author":"Li","year":"2015","journal-title":"Aquaculture"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"734840","DOI":"10.1016\/j.aquaculture.2019.734840","article-title":"Screening of hypoxia-tolerance related SNP in a selectively bred F5 strain of blunt snout bream (Megalobrama amblycephala)","volume":"519","author":"Wang","year":"2020","journal-title":"Aquaculture"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/ng.3097","article-title":"Defining the role of common variation in the genomic and biological architecture of adult human height","volume":"46","author":"Wood","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"(2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511, 421\u2013427.","DOI":"10.1038\/nature13595"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.molp.2023.09.010","article-title":"TBtools-II: A \u201cone for all, all for one\u201d bioinformatics platform for biological big-data mining","volume":"16","author":"Chen","year":"2023","journal-title":"Mol. Plant"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cbpb.2016.06.012","article-title":"Mechanisms of cortisol action in fish hepatocytes","volume":"199","author":"Faught","year":"2016","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1023\/A:1008924418720","article-title":"Cortisol in teleosts: Dynamics, mechanisms of action, and metabolic regulation","volume":"9","author":"Mommsen","year":"1999","journal-title":"Rev. Fish Biol. Fish."},{"key":"ref_28","unstructured":"Li, X. (2018). Effects of Hypoxia Stress on Energy Metabolism, Blood Indices and Gene Expression in the Dark-Striped Oriental Leatherback (Puffer montanus). [Master\u2019s Thesis, Nanjing Normal University]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135157","DOI":"10.1016\/j.scitotenv.2019.135157","article-title":"Acute hypoxia changes the mode of glucose and lipid utilization in the liver of the largemouth bass (Micropterus salmoides)","volume":"713","author":"Sun","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.fsi.2017.06.035","article-title":"Acute hypoxic stress: Effect on blood parameters, antioxidant enzymes, and expression of HIF-1alpha and GLUT-1 genes in largemouth bass (Micropterus salmoides)","volume":"67","author":"Yang","year":"2017","journal-title":"Fish Shellfish Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1532-0456(02)00080-7","article-title":"Animal response to drastic changes in oxygen availability and physiological oxidative stress","volume":"133","year":"2002","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R224","DOI":"10.1152\/ajpregu.00189.2009","article-title":"Physiological consequences of gill remodeling in goldfish (Carassius auratus) during exposure to long-term hypoxia","volume":"66","author":"Mitrovic","year":"2009","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, J., Zhou, Z., Cai, X., Song, Y., Li, Z., Li, Z., Xiao, W., and Wang, J. (2024). Zebrafish usp3 loss promotes hypoxic tolerance by disrupting deubiquitination of K63-polyubiquitinated hif-1\u03b1a. Water Biol. Secur., 3.","DOI":"10.1016\/j.watbs.2024.100245"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1161\/01.STR.0000136149.81831.c5","article-title":"Apoptotic and Necrotic Death Mechanisms Are Concomitantly Activated in the Same Cell After Cerebral Ischemia","volume":"35","author":"Can","year":"2004","journal-title":"Stroke"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00004647-200202000-00001","article-title":"Molecular pathways of protein synthesis inhibition during brain reperfusion: Implications for neuronal survival or death","volume":"22","author":"DeGracia","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.dci.2010.06.011","article-title":"Molecular cloning, characterization and expression analysis of cathepsin C gene involved in the antibacterial response in Chinese mitten crab, Eriocheir sinensis","volume":"34","author":"Li","year":"2010","journal-title":"Dev. Comp. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.dci.2014.04.012","article-title":"Identification, expression, and responses to bacterial challenge of the cathepsin C gene from the razor clam Sinonovacula constricta","volume":"46","author":"Niu","year":"2014","journal-title":"Dev. Comp. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.cbpa.2008.04.001","article-title":"Molecular cloning and mRNA expression of cathepsin C gene in black tiger shrimp (Penaeus monodon)","volume":"150","author":"Qiu","year":"2008","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.fsi.2018.10.027","article-title":"Characterization of cathepsin C from orange-spotted grouper, Epinephelus coioides involved in SGIV infection","volume":"84","author":"Wei","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1515\/bchm3.1992.373.2.367","article-title":"The primary structure and tissue distribution of cathepsin C","volume":"373","author":"Kominami","year":"1992","journal-title":"Biol. Chem. Hoppe Seyler"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.fsi.2022.07.078","article-title":"Cathepsin C (CTSC) contributes to the antibacterial immunity in golden pompano (Trachinotus ovatus)","volume":"128","author":"Diao","year":"2022","journal-title":"Fish Shellfish Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/S1286-4579(00)01326-5","article-title":"Hijacking of apoptotic pathwaysby bacterial pathogens","volume":"2","author":"Gao","year":"2000","journal-title":"Microbes Infect."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Szczesny-Malysiak, E., Dybas, J., Blat, A., Bulat, K., Kus, K., Kaczmarska, M., Wajda, A., Malek, K., Chlopicki, S., and Marzec, K.M. (2020). Irreversible alterations in the hemoglobin structure affect oxygen binding in human packed red blood cells. Biochim. Biophys. Acta (BBA) Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2020.118803"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1242\/jeb.059907","article-title":"Hypoxia-induced mobilization of stored triglycerides in the euryoxic goby Gillichthys mirabilis","volume":"214","author":"Gracey","year":"2011","journal-title":"J. Exp. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cbpc.2005.01.005","article-title":"Molecular cloning and seasonal expression of oyster glycogen phosphorylase and glycogen synthase genes","volume":"140","author":"Bacca","year":"2005","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.cbpb.2003.10.017","article-title":"Hepatopancreas gluconeogenesis and glycogen content during fasting in crabs previously maintained on a high-protein or carbohydrate-rich diet","volume":"137","author":"Oliveira","year":"2004","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.fsi.2019.08.003","article-title":"Molecular cloning and modeling of the Tp53-induced glycolysis and apoptotic regulator (TIGAR) from the Pacific white shrimp Litopenaeus vannamei and its expression in response to hypoxia","volume":"93","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cbpa.2013.02.002","article-title":"Excess post-hypoxic oxygen consumption is independent from lactate accumulation in two cyprinid fishes","volume":"165","author":"Genz","year":"2013","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_49","first-page":"735","article-title":"Mechanisms and evolution of hypoxia tolerance in fish","volume":"276","author":"Mandic","year":"2009","journal-title":"Proc. Biol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.3892\/mmr.2020.11613","article-title":"Attenuation of the Na\/K-ATPase\/Src\/ROS amplification signaling pathway by astaxanthin ameliorates myocardial cell oxidative stress injury","volume":"22","author":"Qu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yu, J., Fu, Y., Gao, J., Zhang, Q., Zhang, N., Zhang, Z., Jiang, X., Chen, C., and Wen, Z. (2024). Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury. Redox Biol., 74.","DOI":"10.1016\/j.redox.2024.103231"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/nrg3118","article-title":"Rare and common variants: Twenty arguments","volume":"13","author":"Gibson","year":"2012","journal-title":"Nat. Rev. Genet."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/4\/532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:32:32Z","timestamp":1760027552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/4\/532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ani15040532"],"URL":"https:\/\/doi.org\/10.3390\/ani15040532","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}