{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:25:40Z","timestamp":1790115940348,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["SAF2011-29051"],"award-info":[{"award-number":["SAF2011-29051"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["19875\/GERM\/15"],"award-info":[{"award-number":["19875\/GERM\/15"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"European Community FEDER","award":["SAF2011-29051"],"award-info":[{"award-number":["SAF2011-29051"]}]},{"name":"European Community FEDER","award":["19875\/GERM\/15"],"award-info":[{"award-number":["19875\/GERM\/15"]}]},{"name":"European Community FEDER","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"European Community FEDER","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Seneca Foundation (Autonomous Community of Murcia)","award":["SAF2011-29051"],"award-info":[{"award-number":["SAF2011-29051"]}]},{"name":"Seneca Foundation (Autonomous Community of Murcia)","award":["19875\/GERM\/15"],"award-info":[{"award-number":["19875\/GERM\/15"]}]},{"name":"Seneca Foundation (Autonomous Community of Murcia)","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Seneca Foundation (Autonomous Community of Murcia)","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["SAF2011-29051"],"award-info":[{"award-number":["SAF2011-29051"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["19875\/GERM\/15"],"award-info":[{"award-number":["19875\/GERM\/15"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["SAF2011-29051"],"award-info":[{"award-number":["SAF2011-29051"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["19875\/GERM\/15"],"award-info":[{"award-number":["19875\/GERM\/15"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Institute of Health \u201cCarlos III\u201d (ISCIII)","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Fondo Europeo de Desarrollo Regional-FEDER","award":["SAF2011-29051"],"award-info":[{"award-number":["SAF2011-29051"]}]},{"name":"Fondo Europeo de Desarrollo Regional-FEDER","award":["19875\/GERM\/15"],"award-info":[{"award-number":["19875\/GERM\/15"]}]},{"name":"Fondo Europeo de Desarrollo Regional-FEDER","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]},{"name":"Fondo Europeo de Desarrollo Regional-FEDER","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Alterations in the neural polyamine system are known to be associated with different brain pathological conditions. In addition, the regulation of enzymes involved in polyamine metabolism such as ornithine decarboxylase (ODC), antizymes (AZs), and antizyme inhibitors (AZINs) is critical during brain development. However, while most studies focus on ODC and AZs, less is known about AZIN expression and function in the brain. Thus, our aim was to analyze the expression pattern of AZIN2 during postnatal development, its brain distribution, and its possible implication in phenotypical alterations. Methods: The expression pattern of Azin2 and other genes related to polyamine metabolism was analyzed by RT-qPCR. \u03b2-D-galactosidase staining was used to determine the anatomical distribution of AZIN2 in a Azin2 knockout model containing the \u03b2Geo marker. Brain polyamine content was determined by HPLC. The Rota-Rod and Pole functional tests were used to evaluate motor skills in Azin2-lacking mice. Results: Our results showed that expression of genes codifying for AZs and AZINs showed a similar increasing pattern over time that coincided with a decrease in ODC activity and putrescine levels. The analysis of AZIN2 distribution demonstrated that it is strongly expressed in the cerebellum and distributed along the neuron body and dendrites. The ablation of Azin2 showed a decrease in putrescine levels and is related to reduced motor skills. Conclusions: Our study revealed that AZIN2 expression in the brain is particularly limited to the cerebellum. In addition, the ablation of Azin2 leads to a reduction in putrescine that relates to alterations in motor function, suggesting the role of AZIN2 in the functioning of dopaminergic neurons.<\/jats:p>","DOI":"10.3390\/biom13010014","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T01:33:12Z","timestamp":1671672792000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-2218","authenticated-orcid":false,"given":"Ana","family":"Lambertos","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-2767","authenticated-orcid":false,"given":"Maria Angeles","family":"Nu\u00f1ez-Sanchez","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"L\u00f3pez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Airway Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s Joaqu\u00edn","family":"L\u00f3pez-Contreras","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-5449","authenticated-orcid":false,"given":"Bruno","family":"Ramos-Molina","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-1056","authenticated-orcid":false,"given":"Rafael","family":"Pe\u00f1afiel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","article-title":"Functions of Polyamines in Mammals","volume":"291","author":"Pegg","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1046\/j.1471-4159.2003.01558.x","article-title":"Polyamine transport, accumulation, and release in brain","volume":"84","author":"Masuko","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18789","DOI":"10.1074\/jbc.TM118.003794","article-title":"Polyamine-mediated channel block of ionotropic glutamate receptors and its regulation by auxiliary proteins","volume":"293","author":"Bowie","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1038\/s41467-020-16629-3","article-title":"Polyamine regulation of ion channel assembly and implications for nicotinic acetylcholine receptor pharmacology","volume":"11","author":"Dhara","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3389\/fphys.2014.00325","article-title":"Inward rectifiers and their regulation by endogenous polyamines","volume":"5","author":"Baronas","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1523\/JNEUROSCI.4351-10.2011","article-title":"Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis","volume":"31","author":"Duan","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0304-3940(95)11881-V","article-title":"Brain polyamine levels are altered in Alzheimer\u2019s disease","volume":"197","author":"Morrison","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/jnnp.71.1.88","article-title":"Polyamine metabolism in brain tumours: Diagnostic relevance of quantitative biochemistry","volume":"71","author":"Ernestus","year":"2001","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1073\/pnas.082609299","article-title":"Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal","volume":"99","author":"Ivanova","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","first-page":"3","article-title":"Polyamines: The possible missing link between mental disorders and epilepsy (Review)","volume":"45","author":"Baroli","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cervelli, M., Averna, M., Vergani, L., Pedrazzi, M., Amato, S., Fiorucci, C., Rossi, M.N., Maura, G., Mariottini, P., and Cervetto, C. (2022). The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071756"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14529","DOI":"10.1074\/jbc.R500031200","article-title":"Regulation of ornithine decarboxylase","volume":"281","author":"Pegg","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18730","DOI":"10.1074\/jbc.TM118.003339","article-title":"The antizyme family for regulating polyamines","volume":"293","author":"Kahana","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0092-8674(95)90450-6","article-title":"Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme","volume":"80","author":"Matsufuji","year":"1995","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ramos-Molina, B., Lambertos, A., and Penafiel, R. (2018). Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications. Med. Sci., 6.","DOI":"10.3390\/medsci6040089"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1042\/bj2500797","article-title":"Changes in ornithine decarboxylase and antizyme activities in developing mouse brain","volume":"250","author":"Onoue","year":"1988","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1159\/000111298","article-title":"Expression of the genes coding for ornithine decarboxylase and its regulatory protein antizyme in the developing rat brain","volume":"17","author":"Pujic","year":"1995","journal-title":"Dev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/1097-4547(20001201)62:5<675::AID-JNR6>3.0.CO;2-S","article-title":"Expression of ODC and its regulatory protein antizyme in the adult rat brain","volume":"62","author":"Kilpelainen","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00726-011-1031-y","article-title":"Differential expression of ornithine decarboxylase antizyme inhibitors and antizymes in rodent tissues and human cell lines","volume":"42","author":"Cremades","year":"2012","journal-title":"Amino Acids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0304-3940(95)11925-M","article-title":"The expression of ornithine decarboxylase antizyme mRNA and protein in rat motoneurons","volume":"197","author":"Junttila","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ygcen.2017.03.005","article-title":"Expression of ODC1, SPD, SPM and AZIN1 in the hypothalamus, ovary and uterus during rat estrous cycle","volume":"246","author":"Fernandes","year":"2017","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1210\/en.2015-1074","article-title":"Control of Polyamine Biosynthesis by Antizyme Inhibitor 1 Is Important for Transcriptional Regulation of Arginine Vasopressin in the Male Rat Hypothalamus","volume":"156","author":"Greenwood","year":"2015","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/j.1750-3639.2009.00334.x","article-title":"Brain neurons express ornithine decarboxylase-activating antizyme inhibitor 2 with accumulation in Alzheimer\u2019s disease","volume":"20","author":"Makitie","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e126299","DOI":"10.1172\/JCI126299","article-title":"Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology","volume":"131","author":"Kovalenko","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.bbagen.2003.11.006","article-title":"Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine","volume":"1670","author":"Zhu","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1042\/bj20040035","article-title":"Putrescine biosynthesis in mammalian tissues","volume":"379","author":"Coleman","year":"2004","journal-title":"Biochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30896","DOI":"10.1074\/jbc.M602840200","article-title":"Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity","volume":"281","author":"Cremades","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1042\/BJ20071004","article-title":"Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase","volume":"409","author":"Kanerva","year":"2008","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lopez-Garcia, C., Ramos-Molina, B., Lambertos, A., Lopez-Contreras, A.J., Cremades, A., and Penafiel, R. (2013). Antizyme inhibitor 2 hypomorphic mice. New patterns of expression in pancreas and adrenal glands suggest a role in secretory processes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069188"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3040281","article-title":"Kinetic mechanism and characterization of human beta-galactosidase precursor secreted by permanently transfected Chinese hamster ovary cells","volume":"304","author":"Zhang","year":"1994","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11065-010-9148-4","article-title":"The basics of brain development","volume":"20","author":"Stiles","year":"2010","journal-title":"Neuropsychol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.cell.2020.04.008","article-title":"Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits","volume":"181","author":"Sanes","year":"2020","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/0006-291X(92)90707-R","article-title":"Developmental expression of ornithine and S-adenosylmethionine decarboxylases in mouse brain","volume":"184","author":"Suorsa","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","first-page":"102","article-title":"Implication of the polyamine system in mental disorders","volume":"33","author":"Fiori","year":"2008","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_35","first-page":"519","article-title":"Changes in liver gene expression of Azin1 knock-out mice","volume":"65","author":"Wan","year":"2010","journal-title":"Z. F\u00fcr Nat. C J. Biosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2443.2008.01249.x","article-title":"Role of ornithine decarboxylase antizyme inhibitor in vivo","volume":"14","author":"Tang","year":"2009","journal-title":"Genes Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1002\/jnr.24053","article-title":"An exercise in brain genoarchitectonics: Analysis of AZIN2-Lacz expressing neuronal populations in the mouse hindbrain","volume":"96","author":"Lambertos","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Rasila, T., Lehtonen, A., Kanerva, K., Makitie, L.T., Haglund, C., and Andersson, L.C. (2016). Expression of ODC Antizyme Inhibitor 2 (AZIN2) in Human Secretory Cells and Tissues. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151175"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/j.yexcr.2010.02.021","article-title":"Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking","volume":"316","author":"Kanerva","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s00726-015-1957-6","article-title":"A role for antizyme inhibitor in cell proliferation","volume":"47","author":"Silva","year":"2015","journal-title":"Amino Acids"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16970","DOI":"10.1073\/pnas.1011751107","article-title":"Polyamine pathway contributes to the pathogenesis of Parkinson disease","volume":"107","author":"Lewandowski","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10770","DOI":"10.18632\/aging.202928","article-title":"Alzheimer\u2019s disease as a chronic maladaptive polyamine stress response","volume":"13","author":"Polis","year":"2021","journal-title":"Aging"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Prokop, J.W., Bupp, C.P., Frisch, A., Bilinovich, S.M., Campbell, D.B., Vogt, D., Schultz, C.R., Uhl, K.L., VanSickle, E., and Rajasekaran, S. (2021). Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development. Genes, 12.","DOI":"10.3390\/genes12040470"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1042\/bj2780895","article-title":"Characterization of a transgenic mouse line over-expressing the human ornithine decarboxylase gene","volume":"278","author":"Halmekyto","year":"1991","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rieck, J., Skatchkov, S.N., Derst, C., Eaton, M.J., and Veh, R.W. (2022). Unique Chemistry, Intake, and Metabolism of Polyamines in the Central Nervous System (CNS) and Its Body. Biomolecules, 12.","DOI":"10.3390\/biom12040501"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s12311-013-0511-x","article-title":"Consensus paper: The cerebellum\u2019s role in movement and cognition","volume":"13","author":"Koziol","year":"2014","journal-title":"Cerebellum"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1113\/JP276794","article-title":"Interneuronal NMDA receptors regulate long-term depression and motor learning in the cerebellum","volume":"597","author":"Kono","year":"2019","journal-title":"J. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rioult-Pedotti, M.S., Pekanovic, A., Atiemo, C.O., Marshall, J., and Luft, A.R. (2015). Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124986"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/nn.4661","article-title":"Viewpoints: How the hippocampus contributes to memory, navigation and cognition","volume":"20","author":"Lisman","year":"2017","journal-title":"Nat. Neurosci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/1\/14\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:45:30Z","timestamp":1760147130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/1\/14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["biom13010014"],"URL":"https:\/\/doi.org\/10.3390\/biom13010014","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,21]]}}}