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Acute dysregulation of oxidative glucose metabolism within the first hours after injury is a hallmark of TBI. The developing brain relies on ketones as well as glucose for energy. Thus, the aim of this study was to determine the metabolism of ketones early after TBI injury in the developing brain. Following the controlled cortical impact injury model of TBI, 21-22-day-old rats were infused with [2,4-13C]\u03b2-hydroxybutyrate during the acute (4 h) period after injury. Using ex vivo 13C-NMR spectroscopy, we determined that 13C-\u03b2-hydroxybutyrate (13C-BHB) metabolism was increased in both the ipsilateral and contralateral sides of the brain after TBI. Incorporation of the label was significantly higher in glutamate than glutamine, indicating that 13C-BHB metabolism was higher in neurons than astrocytes in both sham and injured brains. Our results show that (i) ketone metabolism was significantly higher in both the ipsilateral and contralateral sides of the injured brain after TBI; (ii) ketones were extensively metabolized by both astrocytes and neurons, albeit higher in neurons; (iii) the pyruvate recycling pathway determined by incorporation of the label from the metabolism of 13C-BHB into lactate was upregulated in the immature brain after TBI.<\/jats:p>","DOI":"10.3390\/metabo12080710","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T02:06:42Z","timestamp":1659319602000},"page":"710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Metabolism of Exogenous [2,4-13C]\u03b2-Hydroxybutyrate following Traumatic Brain Injury in 21-22-Day-Old Rats: An Ex Vivo NMR Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Susanna","family":"Scafidi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Jernberg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Fiskum","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Shock Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5236-3853","authenticated-orcid":false,"given":"Mary C.","family":"McKenna","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Faul, M., Xu, L., Wald, M.M., and Coronado, V.G. (2010). Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002\u20132006.","DOI":"10.15620\/cdc.5571"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1007\/s11064-015-1600-7","article-title":"Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns","volume":"40","author":"McKenna","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1159\/000320085","article-title":"Pathophysiological response to experimental diffuse brain trauma differs as a function of developmental age","volume":"32","author":"Cernak","year":"2010","journal-title":"Dev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3109\/17518420903087558","article-title":"Hitting a moving target: Basic mechanisms of recovery from acquired developmental brain injury","volume":"12","author":"Giza","year":"2009","journal-title":"Dev. Neurorehabil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1097\/01.TA.0000162630.78386.98","article-title":"Functional status after childhood traumatic brain injury","volume":"58","author":"Wechsler","year":"2005","journal-title":"J. Trauma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1017\/S1355617713000398","article-title":"Social outcomes in pediatric traumatic brain injury: Perspectives from social neuroscience and developmental psychology","volume":"19","author":"Yeates","year":"2013","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/sj.jcbfm.9600073","article-title":"Metabolic crisis without brain ischemia is common after traumatic brain injury: A combined microdialysis and positron emission tomography study","volume":"25","author":"Vespa","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/jcbfm.2014.177","article-title":"Glycolysis and the pentose phosphate pathway after human traumatic brain injury: Microdialysis studies using 1,2-(13)C2 glucose","volume":"35","author":"Jalloh","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1089\/neu.2006.0038","article-title":"Glucose metabolism after traumatic brain injury: Estimation of pyruvate carboxylase and pyruvate dehydrogenase flux by mass isotopomer analysis","volume":"24","author":"Bartnik","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1089\/neu.2013.3007","article-title":"Cerebral glucose metabolism in an immature rat model of pediatric traumatic brain injury","volume":"30","author":"Robertson","year":"2013","journal-title":"J. Neurotrauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1471-4159.2009.05896.x","article-title":"Delayed cerebral oxidative glucose metabolism after traumatic brain injury in young rats","volume":"109","author":"Scafidi","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1089\/neu.2007.0481","article-title":"Early and sustained alterations in cerebral metabolism after traumatic brain injury in immature rats","volume":"25","author":"Casey","year":"2008","journal-title":"J. Neurotrauma"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1089\/neu.2006.0210","article-title":"The fate of glucose during the period of decreased metabolism after fluid percussion injury: A 13C NMR study","volume":"24","author":"Bartnik","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.expneurol.2009.04.030","article-title":"Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury","volume":"218","author":"Robertson","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/0006-8993(91)90755-K","article-title":"Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: Evidence of a hyper- and subsequent hypometabolic state","volume":"561","author":"Yoshino","year":"1991","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1089\/089771500415409","article-title":"Cerebral metabolic response to traumatic brain injury sustained early in development: A 2-deoxy-D-glucose autoradiographic study","volume":"17","author":"Thomas","year":"2000","journal-title":"J. Neurotrauma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/j.1471-4159.2007.04489.x","article-title":"Mitochondrial dysfunction early after traumatic brain injury in immature rats","volume":"101","author":"Robertson","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_18","unstructured":"Brady, S., Siegel, G.J., Albers, W.R., and Price, D. (2012). Energy metabolism of the brain. Basic Neurochemistry: Principles of Molecular, Cellular and Medical Neurobiology, Academic Press. [8th ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/epi4.12225","article-title":"Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group","volume":"3","author":"Kossoff","year":"2018","journal-title":"Epilepsia Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11064-016-2099-2","article-title":"beta-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms","volume":"42","author":"Achanta","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lim, S., Chesser, A.S., Grima, J.C., Rappold, P.M., Blum, D., Przedborski, S., and Tieu, K. (2011). D-beta-hydroxybutyrate is protective in mouse models of Huntington\u2019s disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024620"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1126\/science.1227166","article-title":"Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor","volume":"339","author":"Shimazu","year":"2013","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/jnc.12975","article-title":"The metabolic impact of beta-hydroxybutyrate on neurotransmission: Reduced glycolysis mediates changes in calcium responses and KATP channel receptor sensitivity","volume":"132","author":"Lund","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1016\/j.biomaterials.2007.04.046","article-title":"The effect of 3-hydroxybutyrate and its derivatives on the growth of glial cells","volume":"28","author":"Xiao","year":"2007","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1172\/JCI200318797","article-title":"D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease","volume":"112","author":"Tieu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.jcbfm.9600543","article-title":"Cerebral metabolic adaptation and ketone metabolism after brain injury","volume":"28","author":"Prins","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1194\/jlr.R046706","article-title":"The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury","volume":"55","author":"Prins","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1177\/0271678X15610584","article-title":"Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity","volume":"36","author":"Greco","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1002\/jnr.21628","article-title":"Fasting is neuroprotective following traumatic brain injury","volume":"86","author":"Davis","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/jnr.20633","article-title":"Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury","volume":"82","author":"Prins","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1089\/neu.2011.1822","article-title":"Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury","volume":"28","author":"Prins","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113289","DOI":"10.1016\/j.expneurol.2020.113289","article-title":"Alternative substrate metabolism depends on cerebral metabolic state following traumatic brain injury","volume":"329","author":"Greco","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1097\/00004647-200207000-00014","article-title":"[2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain","volume":"22","author":"Pan","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.neuint.2005.12.037","article-title":"Neuronal-glial interactions in rats fed a ketogenic diet","volume":"48","author":"Melo","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/nbm.1940060406","article-title":"Cerebral metabolism of [1,2-13C2]glucose and [U-13C4]3-hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy","volume":"6","author":"Kunnecke","year":"1993","journal-title":"NMR Biomed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12916","DOI":"10.1016\/S0021-9258(19)38247-X","article-title":"Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C NMR","volume":"265","author":"Cerdan","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1007\/s11064-017-2173-4","article-title":"Twenty-seven Years of Cerebral Pyruvate Recycling","volume":"42","author":"Cerdan","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-1-4939-3816-2_11","article-title":"The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol","volume":"1462","author":"Osier","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.expneurol.2017.11.003","article-title":"Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury","volume":"300","author":"Pischiutta","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3389\/fneur.2014.00100","article-title":"A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice","volume":"5","author":"Chen","year":"2014","journal-title":"Front. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1089\/neu.2013.2928","article-title":"Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study","volume":"30","author":"Selwyn","year":"2013","journal-title":"J. Neurotrauma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fendo.2017.00231","article-title":"Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice","volume":"8","author":"Zhou","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/jnr.24097","article-title":"Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury","volume":"96","author":"Mannino","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11682-013-9231-6","article-title":"Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury","volume":"7","author":"Wright","year":"2013","journal-title":"Brain Imaging Behav."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1471-4159.2009.06115.x","article-title":"Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons","volume":"110","author":"Lund","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/jnr.490180407","article-title":"Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture","volume":"18","author":"Edmond","year":"1987","journal-title":"J. Neurosci. Res."},{"key":"ref_47","first-page":"2359","article-title":"Ketone body metabolism in the neonate: Development and the effect of diet","volume":"44","author":"Edmond","year":"1985","journal-title":"Fed. Proc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1007\/s11064-011-0485-3","article-title":"[2,4-(13)C]beta-hydroxybutyrate metabolism in astrocytes and C6 glioblastoma cells","volume":"36","author":"Eloqayli","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1007\/s11064-017-2228-6","article-title":"beta-Hydroxybutyrate Boosts Mitochondrial and Neuronal Metabolism but is not Preferred Over Glucose Under Activated Conditions","volume":"42","author":"Achanta","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000112122","article-title":"Energy metabolism in cortical synaptic terminals from weanling and mature rat brain: Evidence for multiple compartments of tricarboxylic acid cycle activity","volume":"16","author":"McKenna","year":"1994","journal-title":"Dev. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1007\/s11064-012-0901-3","article-title":"Substrate competition studies demonstrate oxidative metabolism of glucose, glutamate, glutamine, lactate and 3-hydroxybutyrate in cortical astrocytes from rat brain","volume":"37","author":"McKenna","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/BF02533318","article-title":"Ketone bodies serve as important precursors of brain lipids in the developing rat","volume":"12","author":"Yeh","year":"1977","journal-title":"Lipids"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E1127","DOI":"10.1152\/ajpendo.00187.2003","article-title":"Developmental switch in brain nutrient transporter expression in the rat","volume":"285","author":"Vannucci","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E20","DOI":"10.1152\/ajpendo.00294.2001","article-title":"Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients","volume":"283","author":"Blomqvist","year":"2002","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.plefa.2003.07.006","article-title":"Brain uptake and metabolism of ketone bodies in animal models","volume":"70","author":"Nehlig","year":"2004","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0006-291X(71)80111-0","article-title":"Coenzyme A transferase activity in rat brain","volume":"43","author":"Tildon","year":"1971","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1042\/bj1320731","article-title":"The acetoacetyl-coenzyme A thiolases of rat brain and their relative activities during postnatal development","volume":"132","author":"Middleton","year":"1973","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0197-0186(87)90179-3","article-title":"Ketone body enzyme activities in purified neurons, astrocytes and oligodendroglia","volume":"10","author":"Chechik","year":"1987","journal-title":"Neurochem. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1159\/000094170","article-title":"Induction of monocarboxylate transporter 2 expression and ketone transport following traumatic brain injury in juvenile and adult rats","volume":"28","author":"Prins","year":"2006","journal-title":"Dev. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/jcbfm.2015.29","article-title":"Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: An integrated study using (1)H- and (13)C-NMR spectroscopy","volume":"35","author":"Roy","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1038\/jcbfm.2011.91","article-title":"Cortical substrate oxidation during hyperketonemia in the fasted anesthetized rat in vivo","volume":"31","author":"Jiang","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/jcbfm.2014.77","article-title":"The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo","volume":"34","author":"Chowdhury","year":"2014","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9293","DOI":"10.1523\/JNEUROSCI.0711-20.2020","article-title":"betaOHB Protective Pathways in Aralar-KO Neurons and Brain: An Alternative to Ketogenic Diet","volume":"40","author":"Casarejos","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1046\/j.1471-4159.1998.70062613.x","article-title":"Ontogeny and cellular localization of the pyruvate recycling system in rat brain","volume":"70","author":"Cruz","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/j.1471-4159.2010.06807.x","article-title":"Metabolism of acetyl-L-carnitine for energy and neurotransmitter synthesis in the immature rat brain","volume":"114","author":"Scafidi","year":"2010","journal-title":"J. Neurochem."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/8\/710\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:59:15Z","timestamp":1760140755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/8\/710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":65,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["metabo12080710"],"URL":"https:\/\/doi.org\/10.3390\/metabo12080710","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,29]]}}}