{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:37:18Z","timestamp":1791819438156,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China (NSFC)","award":["32160818"],"award-info":[{"award-number":["32160818"]}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["2021GXNSFAA196001"],"award-info":[{"award-number":["2021GXNSFAA196001"]}]},{"name":"Natural Science Foundation of Guangxi Province","award":["32160818"],"award-info":[{"award-number":["32160818"]}]},{"name":"Natural Science Foundation of Guangxi Province","award":["2021GXNSFAA196001"],"award-info":[{"award-number":["2021GXNSFAA196001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gonadotropin-inhibitory hormone (GnIH) is a reproductive inhibitor and an endogenous orexigenic neuropeptide that may be involved in energy homeostasis and reproduction. However, whether GnIH is a molecular signal link of metabolism and the reproductive system, and thus, regulates reproductive activity as a function of the energy state, is still unknown. In the present study, we investigated the involvement of GnIH in glycolipid metabolism and reproduction in vivo, and in the coupling between these two processes in the testis level. Our results showed that chronic intraperitoneal injection of GnIH into male mice not only increased food intake and altered meal microstructure but also significantly elevated body mass due to the increased mass of liver and epididymal white adipose tissue (eWAT), despite the loss of testicular weight. Furthermore, chronic intraperitoneal administration of GnIH to male mice resulted in obesity-related glycolipid metabolic derangements, showing hyperlipidemia, hyperglycemia, glucose intolerance, and insulin resistance through changes in the expression of glucose and lipid metabolism-related genes in the pancreas and eWAT, respectively. Interestingly, the expression of GnIH and GPR147 was markedly increased in the testis of mice under conditions of energy imbalance, such as fasting, acute hypoglycemia, and hyperglycemia. In addition, chronic GnIH injection markedly inhibited glucose and lipid metabolism of mice testis while significantly decreasing testosterone synthesis and sperm quality, inducing hypogonadism. These observations indicated that orexigenic GnIH triggers hyperphagia-induced obesity-related metabolic derangements and hypogonadism in male mice, suggesting that GnIH is an emerging candidate for coupling metabolism and fertility by involvement in obesity and metabolic disorder-induced reproductive dysfunction of the testes.<\/jats:p>","DOI":"10.3390\/ijms23158066","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T12:53:45Z","timestamp":1658494425000},"page":"8066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Possible Role of GnIH as a Novel Link between Hyperphagia-Induced Obesity-Related Metabolic Derangements and Hypogonadism in Male Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Rongrong","family":"Luo","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Song","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyang","family":"Han","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Zuo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runwen","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlin","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-3856","authenticated-orcid":false,"given":"Xun","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.brainres.2010.08.057","article-title":"Kisspeptins: Bridging energy homeostasis and reproduction","volume":"1364","author":"Castellano","year":"2010","journal-title":"Brain Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000109095","article-title":"Neuropeptide signaling in the integration of metabolism and reproduction","volume":"86","author":"Crown","year":"2007","journal-title":"Neuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cmet.2012.12.003","article-title":"Reproduction, fat metabolism, and life span: What is the connection?","volume":"17","author":"Hansen","year":"2013","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/09513590701582273","article-title":"Metabolic syndrome and reproduction: I. testicular function","volume":"24","author":"Goulis","year":"2008","journal-title":"Gynecol. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/humrep\/dey371","article-title":"Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age","volume":"34","author":"Hart","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.metabol.2013.01.015","article-title":"Kisspeptin as a link between metabolism and reproduction: Evidences from rodent and primate studies","volume":"62","author":"Wahab","year":"2013","journal-title":"Metabolism"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/j.1365-2826.2004.01221.x","article-title":"Galanin-like peptide as a link between metabolism and reproduction","volume":"16","author":"Cunningham","year":"2004","journal-title":"J. Neuroendocrinol."},{"key":"ref_8","first-page":"98","article-title":"Cross-Talk between Metabolism and Reproduction: The Role of POMC and SF1 Neurons","volume":"2","author":"Xu","year":"2011","journal-title":"Front. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1055\/s-0033-1355399","article-title":"Interaction between energy homeostasis and reproduction: Central effects of leptin and ghrelin on the reproductive axis","volume":"45","year":"2013","journal-title":"Horm. Metab. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1006\/bbrc.2000.3350","article-title":"A novel avian hypothalamic peptide inhibiting gonadotropin release","volume":"275","author":"Tsutsui","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tem.2009.11.010","article-title":"Gonadotropin inhibitory hormone function in mammals","volume":"21","author":"Smith","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/icb\/icn019","article-title":"The control of reproductive physiology and behavior by gonadotropin-inhibitory hormone","volume":"48","author":"Ubuka","year":"2008","journal-title":"Integr. Comp. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ygcen.2014.09.002","article-title":"Evolution of gonadotropin-inhibitory hormone receptor and its ligand","volume":"209","author":"Ubuka","year":"2014","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.brainres.2005.05.035","article-title":"Gonadotropin-inhibiting hormone stimulates feeding behavior in chicks","volume":"1050","author":"Tachibana","year":"2005","journal-title":"Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.yhbeh.2006.09.009","article-title":"Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat","volume":"51","author":"Johnson","year":"2007","journal-title":"Horm. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fendo.2020.00194","article-title":"RFRP-3, the Mammalian Ortholog of GnIH, Is a Novel Modulator Involved in Food Intake and Glucose Homeostasis","volume":"11","author":"Huo","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fendo.2016.00006","article-title":"Possible Role of GnIH as a Mediator between Adiposity and Impaired Testicular Function","volume":"7","author":"Anjum","year":"2016","journal-title":"Front. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100900","DOI":"10.1016\/j.yfrne.2021.100900","article-title":"Gonadotropin-inhibitory hormone (GnIH): A new key neurohormone controlling reproductive physiology and behavior","volume":"61","author":"Tsutsui","year":"2021","journal-title":"Front. Neuroendocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100955","DOI":"10.1016\/j.yfrne.2021.100955","article-title":"Advancing reproductive neuroendocrinology through research on the regulation of GnIH and on its diverse actions on reproductive physiology and behavior","volume":"64","author":"Tsutsui","year":"2021","journal-title":"Front. Neuroendocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/rmb2.12272","article-title":"Reproductive neuroendocrinology of mammalian gonadotropin-inhibitory hormone","volume":"18","author":"Ubuka","year":"2019","journal-title":"Reprod. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s11033-021-06198-z","article-title":"RF-amide related peptide-3 (RFRP-3): A novel neuroendocrine regulator of energy homeostasis, metabolism, and reproduction","volume":"48","author":"Anjum","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113438","DOI":"10.1016\/j.ygcen.2020.113438","article-title":"Food access modifies GnIH, but not CRH, cell number in the hypothalamus in a female songbird","volume":"292","author":"Wilsterman","year":"2020","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ygcen.2016.01.004","article-title":"Stimulation of food intake after central administration of gonadotropin-inhibitory hormone is similar in genetically selected low and high body weight lines of chickens","volume":"232","author":"McConn","year":"2016","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1159\/000332822","article-title":"Gonadotropin-inhibitory hormone is a hypothalamic peptide that provides a molecular switch between reproduction and feeding","volume":"95","author":"Clarke","year":"2012","journal-title":"Neuroendocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1210\/en.2011-1110","article-title":"Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone","volume":"153","author":"Ubuka","year":"2012","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1365-2826.2008.01784.x","article-title":"RFamide-related peptide and its cognate receptor in the sheep: cDNA cloning, mRNA distribution in the hypothalamus and the effect of photoperiod","volume":"20","author":"Dardente","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5770","DOI":"10.1210\/en.2008-0581","article-title":"Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: A novel medium for seasonal breeding in the sheep","volume":"149","author":"Smith","year":"2008","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1073\/pnas.0403840102","article-title":"Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain","volume":"102","author":"Ubuka","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ygcen.2012.02.013","article-title":"Gonadotropin-inhibitory hormone (GnIH): Discovery, progress and prospect","volume":"177","author":"Tsutsui","year":"2012","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1210\/jc.2011-2525","article-title":"Clinical review: Regulation of food intake, energy balance, and body fat mass: Implications for the pathogenesis and treatment of obesity","volume":"97","author":"Guyenet","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1467-789X.2008.00477.x","article-title":"Fast food consumption and increased caloric intake: A systematic review of a trajectory towards weight gain and obesity risk","volume":"9","author":"Rosenheck","year":"2008","journal-title":"Obes. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1207\/S15327752JPA8101_04","article-title":"Microstructure of eating behavior associated with Rorschach characteristics in obesity","volume":"81","author":"Elfhag","year":"2003","journal-title":"J. Pers. Assess."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Moriwaki, S., Narimatsu, Y., Fukumura, K., Iwakoshi-Ukena, E., Furumitsu, M., and Ukena, K. (2020). Effects of Chronic Intracerebroventricular Infusion of RFamide-Related Peptide-3 on Energy Metabolism in Male Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228606"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.peptides.2018.07.009","article-title":"RFamide-related peptide-3 promotes alpha TC1 clone 6 cell survival likely via GPR147","volume":"107","author":"Zhang","year":"2018","journal-title":"Peptides"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E653","DOI":"10.1152\/ajpendo.00620.2020","article-title":"100(th) anniversary of the discovery of insulin perspective: Insulin and adipose tissue fatty acid metabolism","volume":"320","author":"Carpentier","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrendo.2010.187","article-title":"The metabolic actions of glucagon revisited","volume":"6","author":"Habegger","year":"2010","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.2337\/db21-0001","article-title":"Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State","volume":"70","author":"Mileti","year":"2021","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1210\/en.2005-1178","article-title":"Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail","volume":"147","author":"Ubuka","year":"2006","journal-title":"Endocrinology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1210\/en.2011-1053","article-title":"Effects of melatonin on peripheral reproductive function: Regulation of testicular GnIH and testosterone","volume":"152","author":"McGuire","year":"2011","journal-title":"Endocrinology"},{"key":"ref_40","first-page":"832","article-title":"Acute fasting-induced repression of the hypothalamic-pituitary-gonadal axis is reversed by RF-9 administration in the adult male macaque","volume":"46","author":"Batool","year":"2014","journal-title":"Horm. Metab. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fendo.2014.00008","article-title":"Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor","volume":"5","author":"Ubuka","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.anireprosci.2015.01.004","article-title":"Developmental changes in the role of gonadotropin-inhibitory hormone (GnIH) and its receptors in the reproductive axis of male Xiaomeishan pigs","volume":"154","author":"Zheng","year":"2015","journal-title":"Anim. Reprod. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1530\/JOE-14-0333","article-title":"Inhibitory roles of the mammalian GnIH ortholog RFRP3 in testicular activities in adult mice","volume":"223","author":"Anjum","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/mrd.10215","article-title":"Sorting specificity of spermatogenic cell specific region of mouse hexokinase-s (mHk1-s)","volume":"64","author":"Nakamura","year":"2003","journal-title":"Mol. Reprod. Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1196\/annals.1397.030","article-title":"Expression of insulin signaling transmitters and glucose transporters at the protein level in the rat testis","volume":"1095","author":"Kokk","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1242\/jcs.02430","article-title":"Germ cells and fatty acids induce translocation of CD36 scavenger receptor to the plasma membrane of Sertoli cells","volume":"118","author":"Gillot","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100543","DOI":"10.1016\/j.repbio.2021.100543","article-title":"Role of peroxisome proliferator-activated receptor gamma (PPARgamma) in the regulation of fatty acid metabolism related gene expressions in testis of men with impaired spermatogenesis","volume":"21","author":"Alizadeh","year":"2021","journal-title":"Reprod. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/cne.24386","article-title":"A hemorrhagic transformation model of mechanical stroke therapy with acute hyperglycemia in mice","volume":"526","author":"Couret","year":"2018","journal-title":"J. Comp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.metabol.2011.06.013","article-title":"Acute hypoglycemia causes depressive-like behaviors in mice","volume":"61","author":"Park","year":"2012","journal-title":"Metabolism"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.peptides.2010.09.027","article-title":"Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals","volume":"32","author":"Goebel","year":"2011","journal-title":"Peptides"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrendo.2013.204","article-title":"Adipose tissue browning and metabolic health","volume":"10","author":"Bartelt","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.peptides.2012.05.008","article-title":"Gonadotropin-inhibitory hormone (GnIH) and its receptor in the female pig: cDNA cloning, expression in tissues and expression pattern in the reproductive axis during the estrous cycle","volume":"36","author":"Li","year":"2012","journal-title":"Peptides"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0890-6238(89)90020-8","article-title":"Effects of fluoride on the histoarchitecture of reproductive organs of the male mouse","volume":"3","author":"Chinoy","year":"1989","journal-title":"Reprod. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/j.1749-6632.1952.tb26576.x","article-title":"Definition of the stages of the cycle of the seminiferous epithelium in the rat","volume":"55","author":"Leblond","year":"1952","journal-title":"Ann. N. Y. Acad Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8066\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:41Z","timestamp":1760140481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":54,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158066"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158066","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}