{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:18:40Z","timestamp":1783549120057,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01HD111557"],"award-info":[{"award-number":["R01HD111557"]}]},{"name":"National Institute of Health","award":["R01HD093701"],"award-info":[{"award-number":["R01HD093701"]}]},{"name":"National Institute of Health","award":["T32HD007186"],"award-info":[{"award-number":["T32HD007186"]}]},{"name":"National Institute of Health","award":["S10OD023553"],"award-info":[{"award-number":["S10OD023553"]}]},{"name":"National Institute of Health","award":["P30-DK116073"],"award-info":[{"award-number":["P30-DK116073"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Postnatally, glucagon acutely lowers plasma amino acid (AA) concentrations by stimulating hepatic AA catabolism, but its fetal actions remain unclear. This study tested whether a 2 h fetal glucagon infusion would stimulate hepatic AA catabolism and inhibit placental AA transfer. Late-gestation pregnant sheep (0.9 gestation) underwent surgical, vascular catheterization and received fetal glucagon (n = 8) or vehicle infusions (n = 8) in a crossover design with a 48 h washout period. Nutrient uptake and utilization were assessed during each infusion, and fetal liver and placental tissue were collected post-infusion under hyperglucagonemic (n = 4) or vehicle (n = 4) conditions. Glucagon receptor was identified in fetal hepatocyte and trophoblast cells. Glucagon reduced fetal plasma AA concentrations by 20% (p = 0.0103) and increased plasma glucose by 47% (p = 0.0152), leading to a three-fold rise in fetal plasma insulin (p = 0.0459). Hepatic gene expression associated with AA catabolism and gluconeogenesis increased (p &lt; 0.0500) following glucagon infusion, and hepatic metabolomic analysis showed enrichment in AA metabolism pathways. However, placental AA transfer was unaffected by 2 h fetal glucagon infusions. In conclusion, a 2 h glucagon infusion stimulates hepatic glucose production and enhances AA catabolism in the fetal liver, lowering plasma AA concentrations. The primary acute effects of fetal glucagon are hepatic, as placental AA transfer is unchanged.<\/jats:p>","DOI":"10.3390\/ijms26051904","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:47:17Z","timestamp":1740379637000},"page":"1904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Two-Hour Fetal Glucagon Infusion Stimulates Hepatic Catabolism of Amino Acids in Fetal Sheep"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-7096","authenticated-orcid":false,"given":"Amelia R.","family":"Tanner","sequence":"first","affiliation":[{"name":"Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4673-1186","authenticated-orcid":false,"given":"Sarah N.","family":"Cilvik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-8283","authenticated-orcid":false,"given":"Marjorie A.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Dobrinskikh","sequence":"additional","affiliation":[{"name":"Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-626X","authenticated-orcid":false,"given":"Russell V.","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R.","family":"Wesolowski","sequence":"additional","affiliation":[{"name":"Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Rozance","sequence":"additional","affiliation":[{"name":"Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrendo.2015.51","article-title":"Islet \u03b1 Cells and Glucagon\u2014Critical Regulators of Energy Homeostasis","volume":"11","author":"Campbell","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1152\/physrev.00028.2023","article-title":"Hepatic Glucagon Action: Beyond Glucose Mobilization","volume":"104","author":"Kajani","year":"2024","journal-title":"Physiol. Rev."},{"key":"ref_3","first-page":"E239","article-title":"Bradykinin Attenuates Glucagon-Induced Leucine Oxidation in Humans","volume":"259","author":"Hartl","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/0026-0495(94)90009-4","article-title":"The Role of Glucagon in the Control of Protein and Amino Acid Metabolism In Vivo","volume":"43","author":"Flakoll","year":"1994","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1172\/JCI118782","article-title":"Evidence for a Catabolic Role of Glucagon During an Amino Acid Load","volume":"98","author":"Charlton","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/jdi.12797","article-title":"Regulation of Amino Acid Metabolism and Alpha-Cell Proliferation by Glucagon","volume":"9","author":"Hayashi","year":"2018","journal-title":"J. Diabetes Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2337\/db16-0994","article-title":"Glucagon and Amino Acids Are Linked in a Mutual Feedback Cycle: The Liver\u2013\u03b1-Cell Axis","volume":"66","author":"Holst","year":"2017","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1159\/000240526","article-title":"Failure of the Human Placenta to Transfer Pancreatic Glucagon","volume":"21","author":"Johnston","year":"1972","journal-title":"Biol. Neonate"},{"key":"ref_9","first-page":"541","article-title":"Endocrine Pancreatic Function in Growth-Retarded Fetuses","volume":"77","author":"Hubinont","year":"1991","journal-title":"Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1210\/en.2005-0900","article-title":"Attenuated Insulin Release and Storage in Fetal Sheep Pancreatic Islets with Intrauterine Growth Restriction","volume":"147","author":"Limesand","year":"2006","journal-title":"Endocrinology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R492","DOI":"10.1152\/ajpregu.00484.2016","article-title":"Chronic Anemic Hypoxemia Attenuates Glucose-Stimulated Insulin Secretion in Fetal Sheep","volume":"312","author":"Benjamin","year":"2017","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1152\/ajpendo.00069.2019","article-title":"Sustained Hypoxemia in Late Gestation Potentiates Hepatic Gluconeogenic Gene Expression but Does Not Activate Glucose Production in the Ovine Fetus","volume":"317","author":"Jones","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1203\/00006450-198003000-00005","article-title":"Adrenergic Modulation of Pancreatic Hormone Secretion in Utero: Studies in Fetal Sheep","volume":"14","author":"Sperling","year":"1980","journal-title":"Pediatr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1159\/000176477","article-title":"Metabolic and Hormonal Response to Chronic Maternal Fasting in the Ewe","volume":"25","author":"Schreiner","year":"1981","journal-title":"Ann. Nutr. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1113\/JP281288","article-title":"Late Gestation Fetal Hyperglucagonaemia Impairs Placental Function and Results in Diminished Fetal Protein Accretion and Decreased Fetal Growth","volume":"599","author":"Cilvik","year":"2021","journal-title":"J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E542","DOI":"10.1152\/ajpendo.00248.2001","article-title":"Fetal Hepatic and Umbilical Uptakes of Glucogenic Substrates during a Glucagon-Somatostatin Infusion","volume":"282","author":"Teng","year":"2002","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6329","DOI":"10.1113\/JP286974","article-title":"Chronic Late Gestation Fetal Hyperglucagonaemia Results in Lower Insulin Secretion, Pancreatic Mass, Islet Area, and Beta- and \u03b1-Cell Proliferation","volume":"602","author":"Cilvik","year":"2024","journal-title":"J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E638","DOI":"10.1152\/ajpendo.00192.2009","article-title":"Prolonged Maternal Amino Acid Infusion in Late-Gestation Pregnant Sheep Increases Fetal Amino Acid Oxidation","volume":"297","author":"Rozance","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E352","DOI":"10.1152\/ajpendo.00377.2012","article-title":"Increased Amino Acid Supply Potentiates Glucose-Stimulated Insulin Secretion but Does Not Increase \u03b2-Cell Mass in Fetal Sheep","volume":"304","author":"Gadhia","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1210\/en.2016-1328","article-title":"Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic Vascularity, and Islet Size in Growth-Restricted Fetal Sheep","volume":"157","author":"Brown","year":"2016","journal-title":"Endocrinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R654","DOI":"10.1152\/ajpregu.00502.2016","article-title":"Exogenous Amino Acids Suppress Glucose Oxidation and Potentiate Hepatic Glucose Production in Late Gestation Fetal Sheep","volume":"312","author":"Brown","year":"2017","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1210\/endo-110-1-227","article-title":"Effects of Glucocorticosteroids and Glucagon on Argininosuccinate Synthetase, Argininosuccinase, and Arginase in Fetal Rat Liver","volume":"110","author":"Husson","year":"1982","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, L., Zhang, P., Bao, Z., Wang, T., Liu, S., and Huang, F. (2016). PGC-1\u03b1 Promotes Ureagenesis in Mouse Periportal Hepatocytes through SIRT3 and SIRT5 in Response to Glucagon. Sci. Rep., 6.","DOI":"10.1038\/srep24156"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22204","DOI":"10.1073\/pnas.2000643117","article-title":"Transcriptome-Wide Analysis of PGC-1\u03b1-Binding RNAs Identifies Genes Linked to Glucagon Metabolic Action","volume":"117","author":"Tavares","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/S0024-3205(98)00435-4","article-title":"Regulation of Histidase Gene Expression by Glucagon, Hydrocortisone, and Protein-Free\/High Carbohydrate Diet in the Rat","volume":"63","author":"Torres","year":"1998","journal-title":"Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e14991","DOI":"10.14814\/phy2.14991","article-title":"Hormonal Regulation of Glycine Decarboxylase and Its Relationship to Oxidative Stress","volume":"9","author":"Jog","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1210\/endo.131.1.1319325","article-title":"Ligand-mediated internalization of glucagon receptors in intact rat liver","volume":"131","author":"Authier","year":"1992","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1016\/j.febslet.2006.09.021","article-title":"Glucagon-Mediated Internalization of Serine-Phosphorylated Glucagon Receptor and Gsalpha in Rat Liver","volume":"580","author":"Merlen","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12986-019-0346-7","article-title":"Evidence for Liver Energy Metabolism Programming in Offspring Subjected to Intrauterine Undernutrition during Midgestation","volume":"16","author":"Zhou","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1007\/s00125-016-3955-y","article-title":"Glucagon: Acute Actions on Hepatic Metabolism","volume":"59","author":"Miller","year":"2016","journal-title":"Diabetologia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E522","DOI":"10.1152\/ajpendo.00420.2011","article-title":"Hypoglycemia, Hyperglucagonemia, and Fetoplacental Defects in Glucagon Receptor Knockout Mice: A Role for Glucagon Action in Pregnancy Maintenance","volume":"302","author":"Ouhilal","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0006-291X(88)80467-4","article-title":"The Human Placenta as a Target Tissue for Glucagon","volume":"151","author":"Perlman","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/jphysiol.1952.sp004770","article-title":"Inability of Diffusion to Account for Placental Glucose Transfer in the Sheep and Consideration of the Kinetics of a Possible Carrier Transfer","volume":"118","author":"Widdas","year":"1952","journal-title":"J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1079\/PNS19910042","article-title":"Energy and Substrate Requirements of the Placenta and Fetus","volume":"50","author":"Hay","year":"1991","journal-title":"Proc. Nutr. Soc."},{"key":"ref_35","first-page":"R569","article-title":"Model of Placental Glucose Consumption and Glucose Transfer","volume":"258","author":"Hay","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_36","first-page":"E256","article-title":"Glucagon and Glucose Dynamics in Sheep: Evidence for Glucagon Resistance in the Fetus","volume":"246","author":"Devaskar","year":"1984","journal-title":"Am. J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R138","DOI":"10.1152\/ajpregu.00223.2020","article-title":"Impact of Chorionic Somatomammotropin RNA Interference on Uterine Blood Flow and Placental Glucose Uptake in the Absence of Intrauterine Growth Restriction","volume":"320","author":"Tanner","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tanner, A.R., Lynch, C.S., Kennedy, V.C., Ali, A., Winger, Q.A., Rozance, P.J., and Anthony, R.V. (2021). CSH RNA Interference Reduces Global Nutrient Uptake and Umbilical Blood Flow Resulting in Intrauterine Growth Restriction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158150"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E602","DOI":"10.1152\/ajpendo.00331.2023","article-title":"Increasing Maternal Glucose Concentrations Is Insufficient to Restore Placental Glucose Transfer in Chorionic Somatomammotropin RNA Interference Pregnancies","volume":"326","author":"Tanner","year":"2024","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1113\/JP281791","article-title":"Back-Seat Driver: The Fetus Is Not a Passive Passenger!","volume":"599","author":"Gatford","year":"2021","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Percie Du Sert, N., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., Dirnagl, U., and Emerson, M. (2020). Reporting Animal Research: Explanation and Elaboration for the ARRIVE Guidelines 2.0. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000411"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1210\/endo.131.6.1446621","article-title":"Quantification and Cellular Localization of Ovine Placental Lactogen Messenger Ribonucleic Acid Expression During Mid- and Late Gestation","volume":"131","author":"Kappes","year":"1992","journal-title":"Endocrinology"},{"key":"ref_43","first-page":"351","article-title":"Growth and Metabolism of the Placenta after Unilateral Fetectomy in Twin Pregnant Ewes","volume":"15","author":"Vatnick","year":"1991","journal-title":"J. Dev. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2144\/05391RV01","article-title":"Real-Time PCR for mRNA Quantitation","volume":"39","author":"Wong","year":"2005","journal-title":"BioTechniques"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.molmet.2018.09.008","article-title":"Switching Obese Mothers to a Healthy Diet Improves Fetal Hypoxemia, Hepatic Metabolites, and Lipotoxicity in Non-Human Primates","volume":"18","author":"Wesolowski","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112393","DOI":"10.1016\/j.celrep.2023.112393","article-title":"Maternal Diet Alters Long-Term Innate Immune Cell Memory in Fetal and Juvenile Hematopoietic Stem and Progenitor Cells in Nonhuman Primate Offspring","volume":"42","author":"Nash","year":"2023","journal-title":"Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/rcm.7834","article-title":"A Three-Minute Method for High-Throughput Quantitative Metabolomics and Quantitative Tracing Experiments of Central Carbon and Nitrogen Pathways","volume":"31","author":"Nemkov","year":"2017","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/trf.13892","article-title":"Citrate Metabolism in Red Blood Cells Stored in Additive Solution-3","volume":"57","author":"Nemkov","year":"2017","journal-title":"Transfusion"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"E1716","DOI":"10.1152\/ajpendo.00459.2007","article-title":"Increased Insulin Sensitivity and Maintenance of Glucose Utilization Rates in Fetal Sheep with Placental Insufficiency and Intrauterine Growth Restriction","volume":"293","author":"Limesand","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2337\/db11-1727","article-title":"Increased Hepatic Glucose Production in Fetal Sheep with Intrauterine Growth Restriction Is Not Suppressed by Insulin","volume":"62","author":"Thorn","year":"2013","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"102849","DOI":"10.1016\/j.xpro.2024.102849","article-title":"Isolating Mononuclear Cells from Fetal Bone and Liver for Metabolic, Functional, and Immunophenotypic Analyses in Nonhuman Primates","volume":"5","author":"Nash","year":"2024","journal-title":"STAR Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1210\/en.2008-1789","article-title":"Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity and Reduces Messenger Ribonucleic Acid Translation Initiation and Nutrient Sensing in Fetal Liver and Skeletal Muscle","volume":"150","author":"Thorn","year":"2009","journal-title":"Endocrinology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R861","DOI":"10.1152\/ajpregu.00331.2012","article-title":"A Physiological Increase in Insulin Suppresses Gluconeogenic Gene Activation in Fetal Sheep with Sustained Hypoglycemia","volume":"303","author":"Thorn","year":"2012","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1904\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:40:39Z","timestamp":1760028039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,22]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26051904"],"URL":"https:\/\/doi.org\/10.3390\/ijms26051904","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,22]]}}}