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The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood. Herein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism in male mice. Liver-brain axis was impaired by vagotomy (VNX) or knocking down of the vesicular acetylcholine transporter (VAChT-KD). Mice were challenged with high carbohydrate or high-fat feeding. The vagus nerve shapes the metabolic framework of the liver, as vagotomy led to a significant alteration of the hepatic proteome landscape. Differential protein expression and pathway enrichment analyses showed that glycolytic and fatty acid biosynthesis were increased following VNX, whereas \u03b2-oxidation was decreased. These results were corroborated in VAChT-KD mice. This metabolic shift facilitated lipid accumulation in hepatocytes in mice fed with a standard commercial diet. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. This study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape.<\/jats:p>","DOI":"10.3390\/ijms26052166","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T04:28:18Z","timestamp":1740716898000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Vagus Nerve Mediated Liver-Brain-Axis Is a Major Regulator of the Metabolic Landscape in the Liver"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1690-6811","authenticated-orcid":false,"given":"Camila F.","family":"Brito","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6676-5335","authenticated-orcid":false,"given":"Roberta C.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-637X","authenticated-orcid":false,"given":"Lucas","family":"Rodrigues-Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o S. 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M.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2597-8737","authenticated-orcid":false,"given":"Rafaela M.","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, College of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C. C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3987-5738","authenticated-orcid":false,"given":"Ivana S.","family":"Lula","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valbert N.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, College of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone O. 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Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/cphy.c120018","article-title":"Hepatic nervous system and neurobiology of the liver","volume":"3","author":"Jensen","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/ar.a.20088","article-title":"Anatomy and function of sensory hepatic nerves","volume":"280A","author":"Berthoud","year":"2004","journal-title":"Anat. Rec."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1172\/JCI78361","article-title":"Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells","volume":"125","author":"Shahid","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"aat5236","DOI":"10.1126\/science.aat5236","article-title":"A gut-brain neural circuit for nutrient sensory transduction","volume":"361","author":"Kaelberer","year":"2018","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1113\/jphysiol.1982.sp014415","article-title":"Glucose-sensitive afferent nerve fibres in the hepatic branch of the vagus nerve in the guinea-pig","volume":"332","author":"Niijima","year":"1982","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"971S","DOI":"10.1093\/jn\/130.4.971S","article-title":"Reflex effects of oral, gastrointestinal and hepatoportal glutamate sensors on vagal nerve activity","volume":"130","author":"Niijima","year":"2000","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1097\/00001756-200110080-00024","article-title":"Jejunal or portal vein infusions of lipids increase hepatic vagal afferent activity","volume":"12","author":"Randich","year":"2001","journal-title":"Neuroreport"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.bbadis.2010.01.006","article-title":"The role of the autonomic nervous liver innervation in the control of energy metabolism","volume":"1802","author":"Yi","year":"2010","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2018.08.049","article-title":"A Neural Circuit for Gut-Induced Reward","volume":"175","author":"Han","year":"2018","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41593-021-00982-7","article-title":"The preference for sugar over sweetener depends on a gut sensor cell","volume":"25","author":"Buchanan","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1113\/JP271538","article-title":"Role of the vagus nerve in the development and treatment of diet-induced obesity","volume":"594","year":"2016","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1212\/WNL.59.3.463","article-title":"Weight loss associated with vagus nerve stimulation","volume":"59","author":"Burneo","year":"2002","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1038\/sj.ijo.0803666","article-title":"Weight loss during chronic, cervical vagus nerve stimulation in depressed patients with obesity: An observation","volume":"31","author":"Pardo","year":"2007","journal-title":"Int. J. Obes."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vijgen, G.H.E.J., Bouvy, N.D., Leenen, L., Rijkers, K., Cornips, E., Majoie, M., Brans, B., and van Marken Lichtenbelt, W.D. (2013). Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077221"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuron.2006.08.005","article-title":"Mice Deficient for the Vesicular Acetylcholine Transporter Are Myasthenic and Have Deficits in Object and Social Recognition","volume":"51","author":"Prado","year":"2006","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1432-1033.1992.tb17063.x","article-title":"Nervous control of liver metabolism and hemodynamics","volume":"207","author":"Gardemann","year":"1992","journal-title":"Eur. J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Seicol, B.J., Bejarano, S., Behnke, N., and Guo, L. (2019). Neuromodulation of metabolic functions: From pharmaceuticals to bioelectronics to biocircuits. J. Biol. Eng., 13.","DOI":"10.1186\/s13036-019-0194-z"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1530\/JOE-22-0320","article-title":"Neural gut-to-brain communication for postprandial control of satiation and glucose metabolism","volume":"258","author":"Cabot","year":"2023","journal-title":"J. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102887","DOI":"10.1016\/j.autneu.2021.102887","article-title":"Functional anatomy of the vagus system\u2014Emphasis on the somato-visceral interface","volume":"236","author":"Neuhuber","year":"2021","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/s41366-018-0086-1","article-title":"The vagus neurometabolic interface and clinical disease","volume":"42","author":"Masi","year":"2018","journal-title":"Int. J. Obes."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/dom.14575","article-title":"Vagal afferent cholecystokinin receptor activation is required for glucagon-like peptide-1\u2013induced satiation","volume":"24","author":"Vana","year":"2022","journal-title":"Diabetes Obes. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101350","DOI":"10.1016\/j.molmet.2021.101350","article-title":"Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid receptor (FFAR3), is necessary for normal feeding behavior","volume":"54","author":"Cook","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1038\/s41467-019-10684-1","article-title":"Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis","volume":"10","author":"Hackl","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1016\/j.cmet.2022.09.020","article-title":"Leptin increases hepatic triglyceride export via a vagal mechanism in humans","volume":"34","author":"Metz","year":"2022","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.metabol.2017.11.002","article-title":"Nicotinic acetylcholine receptor \u03b17 subunit improves energy homeostasis and inhibits inflammation in nonalcoholic fatty liver disease","volume":"79","author":"Li","year":"2018","journal-title":"Metabolism"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1210\/en.2017-00594","article-title":"a7-nicotinic acetylcholine receptor agonist ameliorates nicotine plus high-fat Diet\u2013Induced hepatic steatosis in male mice by inhibiting oxidative stress and stimulating AMPK signaling","volume":"159","author":"Hasan","year":"2018","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/jdi.12964","article-title":"Nicotinic alpha-7 acetylcholine receptor deficiency exacerbates hepatic inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis","volume":"10","author":"Kimura","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gausser\u00e8s, B., Liu, J., Foppen, E., Tourrel-Cuzin, C., Sanchez-Archidona, A.R., Delangre, E., Cruciani-Guglielmacci, C., Pons, S., Maskos, U., and Thorens, B. (2020). The constitutive lack of \u03b17 nicotinic receptor leads to metabolic disorders in mouse. Biomolecules, 10.","DOI":"10.3390\/biom10071057"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jun, H., Liu, S., Knights, A.J., Zhu, K., Ma, Y., Gong, J., Lenhart, A.E., Peng, X., Huang, Y., and Ginder, J.P. (2024). Signaling through the nicotinic acetylcholine receptor in the liver protects against the development of metabolic dysfunction-associated steatohepatitis. PLoS Biol., 22.","DOI":"10.1371\/journal.pbio.3002728"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.bbi.2019.06.041","article-title":"Vagus nerve regulates the phagocytic and secretory activity of resident macrophages in the liver","volume":"81","author":"Fonseca","year":"2019","journal-title":"Brain. Behav. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.bbrc.2020.08.045","article-title":"Chronic high fat diet impairs glucagon like peptide-1 sensitivity in vagal afferents","volume":"533","author":"Park","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Loper, H., Leinen, M., Bassoff, L., Sample, J., Romero-Ortega, M., Gustafson, K.J., Taylor, D.M., and Schiefer, M.A. (2021). Both high fat and high carbohydrate diets impair vagus nerve signaling of satiety. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-89465-0"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.molmet.2014.06.003","article-title":"Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity","volume":"3","author":"Ronveaux","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1113\/expphysiol.2014.082982","article-title":"Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and adult rats","volume":"100","author":"Barella","year":"2015","journal-title":"Exp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S2213-8587(14)70032-4","article-title":"Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome","volume":"2","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/TP.0000000000002485","article-title":"Management of Recurrent and de Novo NAFLD\/NASH after Liver Transplantation","volume":"103","author":"Germani","year":"2019","journal-title":"Transplantation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/lt.20932","article-title":"De novo nonalcoholic fatty liver disease after liver transplantation","volume":"13","author":"Seo","year":"2007","journal-title":"Liver Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ajg.2009.717","article-title":"Non-alcoholic fatty liver disease in liver transplant recipients: Another story of seed and soil","volume":"105","author":"Dumortier","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1097\/MEG.0000000000001105","article-title":"De-novo nonalcoholic steatohepatitis is associated with long-term increased mortality in liver transplant recipients","volume":"30","author":"Gitto","year":"2018","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/path.1711670210","article-title":"Hepatic reinnervation following orthotopic liver transplantation in man","volume":"167","author":"Boon","year":"1992","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41575-023-00771-6","article-title":"Gut\u2013liver axis: Barriers and functional circuits","volume":"20","author":"Pabst","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.autneu.2004.11.012","article-title":"Novel pathway for LPS-induced afferent vagus nerve activation: Possible role of nodose ganglion","volume":"120","author":"Hosoi","year":"2005","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jnutbio.2018.03.009","article-title":"Short-chain fatty acids suppress food intake by activating vagal afferent neurons","volume":"57","author":"Goswami","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111699","DOI":"10.1016\/j.isci.2024.111699","article-title":"Select microbial metabolites in the small intestinal lumen regulates vagal activity via receptor-mediated signaling","volume":"28","author":"Jameson","year":"2025","journal-title":"iScience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e16114","DOI":"10.14814\/phy2.16114","article-title":"Digestive dynamics: Unveiling interplay between the gut microbiota and the liver in macronutrient metabolism and hepatic metabolic health","volume":"12","author":"Kandalgaonkar","year":"2024","journal-title":"Physiol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100744","DOI":"10.1016\/j.jlr.2025.100744","article-title":"Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands","volume":"66","author":"Antunes","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1053\/j.gastro.2016.08.024","article-title":"Combination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation of Liver Myeloid Cells in Mice","volume":"151","author":"David","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cmet.2009.11.002","article-title":"Circadian Clock-Coordinated 12 Hr Period Rhythmic Activation of the IRE1\u03b1 Pathway Controls Lipid Metabolism in Mouse Liver","volume":"11","author":"Cretenet","year":"2010","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nprot.2009.21","article-title":"Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics","volume":"4","author":"Boersema","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1021\/pr101065j","article-title":"Andromeda: A peptide search engine integrated into the MaxQuant environment","volume":"10","author":"Cox","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1093\/bioinformatics\/btz245","article-title":"FuncTree2: An interactive radial tree for functional hierarchies and omics data visualization","volume":"35","author":"Darzi","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"ClusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.bpj.2017.03.011","article-title":"NMRbox: A Resource for Biomolecular NMR Computation","volume":"112","author":"Maciejewski","year":"2017","journal-title":"Biophys. J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pang, Z., Chong, J., Li, S., and Xia, J. (2020). Metaboanalystr 3.0: Toward an optimized workflow for global metabolomics. Metabolites, 10.","DOI":"10.3390\/metabo10050186"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1021\/cb5006382","article-title":"Unified and isomer-specific NMR metabolomics database for the accurate analysis of 13C-1H HSQC spectra","volume":"10","author":"Bingol","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1021\/ac702530t","article-title":"Web server based complex mixture analysis by NMR","volume":"80","author":"Robinette","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Bai","year":"2022","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:44:23Z","timestamp":1760028263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":62,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052166"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052166","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.16.567412","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]}}}