{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:49:18Z","timestamp":1787507358510,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T00:00:00Z","timestamp":1682121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NP-111-PP-08"],"award-info":[{"award-number":["NP-111-PP-08"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["110-0324-01-25-01\/111-0324-01-27-12\/112-0324-01-30-08"],"award-info":[{"award-number":["110-0324-01-25-01\/111-0324-01-27-12\/112-0324-01-30-08"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["MOST-108-2320-B-400-015-MY3"],"award-info":[{"award-number":["MOST-108-2320-B-400-015-MY3"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NSTC-109-2320-B-400-008-MY3"],"award-info":[{"award-number":["NSTC-109-2320-B-400-008-MY3"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Government S&amp;T grant","award":["NP-111-PP-08"],"award-info":[{"award-number":["NP-111-PP-08"]}]},{"name":"Central Government S&amp;T grant","award":["110-0324-01-25-01\/111-0324-01-27-12\/112-0324-01-30-08"],"award-info":[{"award-number":["110-0324-01-25-01\/111-0324-01-27-12\/112-0324-01-30-08"]}]},{"name":"Central Government S&amp;T grant","award":["MOST-108-2320-B-400-015-MY3"],"award-info":[{"award-number":["MOST-108-2320-B-400-015-MY3"]}]},{"name":"Central Government S&amp;T grant","award":["NSTC-109-2320-B-400-008-MY3"],"award-info":[{"award-number":["NSTC-109-2320-B-400-008-MY3"]}]},{"name":"Ministry of Science and Technology grants","award":["NP-111-PP-08"],"award-info":[{"award-number":["NP-111-PP-08"]}]},{"name":"Ministry of Science and Technology grants","award":["110-0324-01-25-01\/111-0324-01-27-12\/112-0324-01-30-08"],"award-info":[{"award-number":["110-0324-01-25-01\/111-0324-01-27-12\/112-0324-01-30-08"]}]},{"name":"Ministry of Science and Technology grants","award":["MOST-108-2320-B-400-015-MY3"],"award-info":[{"award-number":["MOST-108-2320-B-400-015-MY3"]}]},{"name":"Ministry of Science and Technology grants","award":["NSTC-109-2320-B-400-008-MY3"],"award-info":[{"award-number":["NSTC-109-2320-B-400-008-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transient global cerebral ischemia (tGCI) resulting from cardiac arrest causes selective neurodegeneration in hippocampal CA1 neurons. Although the effect is clear, the underlying mechanisms directing this process remain unclear. Previous studies have shown that phosphorylation of Erk1\/2 promotes cell survival in response to tGCI. DUSP6 (also named MKP3) serves as a cytosolic phosphatase that dephosphorylates Erk1\/2, but the role of DUSP6 in tGCI has not been characterized. We found that DUSP6 was specifically induced in the cytoplasm of hippocampal CA1 neurons 4 to 24 h after tGCI. DUSP6-deficient mice showed normal spatial memory acquisition and retention in the Barnes maze. Impairment of spatial memory acquisition and retention after tGCI was attenuated in DUSP6-deficient mice. Neurodegeneration after tGCI, revealed by Fluoro-Jade C and H&amp;E staining, was reduced in the hippocampus of DUSP6-deficient mice and DUSP6 deficiency enhanced the phosphorylation and nuclear translocation of Erk1\/2 in the hippocampal CA1 region. These data support the role of DUSP6 as a negative regulator of Erk1\/2 signaling and indicate the potential of DUSP6 inhibition as a novel therapeutic strategy to treat neurodegeneration after tGCI.<\/jats:p>","DOI":"10.3390\/ijms24097690","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T03:38:07Z","timestamp":1682307487000},"page":"7690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia"],"prefix":"10.3390","volume":"24","author":[{"given":"Yi-Chinn","family":"Weng","sequence":"first","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chen","family":"Chiang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-Chia","family":"Chuang","sequence":"additional","affiliation":[{"name":"Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsong-Hai","family":"Lee","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4969-3170","authenticated-orcid":false,"given":"Tse-Hua","family":"Tan","sequence":"additional","affiliation":[{"name":"Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7899-1129","authenticated-orcid":false,"given":"Wen-Hai","family":"Chou","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s13311-020-00856-z","article-title":"Resuscitating the Globally Ischemic Brain: TTM and Beyond","volume":"17","author":"Hosseini","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, C.Y., Wang, J.Y., Teng, N.C., Chao, T.T., Tsai, S.L., Chen, C.L., Hsu, J.Y., Wu, C.P., Lai, C.C., and Chen, L. (2015). The secular trends in the incidence rate and outcomes of out-of-hospital cardiac arrest in Taiwan\u2014A nationwide population-based study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122675"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s00134-021-06548-2","article-title":"Brain injury after cardiac arrest: Pathophysiology, treatment, and prognosis","volume":"47","author":"Sandroni","year":"2021","journal-title":"Intensiv. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1161\/CIRCULATIONAHA.110.988725","article-title":"Post cardiac arrest syndrome: A review of therapeutic strategies","volume":"123","author":"Stub","year":"2011","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.ajem.2011.03.007","article-title":"Therapeutic hypothermia: A state-of-the-art emergency medicine perspective","volume":"30","author":"Varon","year":"2012","journal-title":"Am. J. Emerg. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1212\/WNL.37.8.1281","article-title":"Delayed hippocampal damage in humans following cardiorespiratory arrest","volume":"37","author":"Petito","year":"1987","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/00004647-200007000-00008","article-title":"Alteration of MAP kinase pathways after transient forebrain ischemia","volume":"20","author":"Hu","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1002\/jnr.21604","article-title":"Dual roles of the MAPK\/ERK1\/2 cell signaling pathway after stroke","volume":"86","author":"Sawe","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.4161\/cc.8.8.8147","article-title":"How ERK1\/2 activation controls cell proliferation and cell death: Is subcellular localization the answer?","volume":"8","author":"Mebratu","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1742-4658.2009.07366.x","article-title":"ERK and cell death: Mechanisms of ERK-induced cell death\u2014Apoptosis, autophagy and senescence","volume":"277","author":"Cagnol","year":"2010","journal-title":"FEBS J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1742-4658.2009.07367.x","article-title":"ERK and cell death: ERK1\/2 in neuronal death","volume":"277","author":"Subramaniam","year":"2010","journal-title":"FEBS J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1042\/BJ20082234","article-title":"Dual-specificity phosphatases: Critical regulators with diverse cellular targets","volume":"418","author":"Patterson","year":"2009","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chen, H.F., Chuang, H.C., and Tan, T.H. (2019). Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112668"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1242\/dev.02701","article-title":"Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development","volume":"134","author":"Li","year":"2007","journal-title":"Development"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.2337\/db14-0066","article-title":"Mitogen-activated protein kinase phosphatase 3 (MKP-3)-deficient mice are resistant to diet-induced obesity","volume":"63","author":"Feng","year":"2014","journal-title":"Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16220","DOI":"10.1038\/nmicrobiol.2016.220","article-title":"Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice","volume":"2","author":"Ruan","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110016","DOI":"10.1016\/j.celrep.2021.110016","article-title":"Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice","volume":"37","author":"Chang","year":"2021","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1172\/JCI43250","article-title":"MAPK phosphatase-3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice","volume":"120","author":"Wu","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.mce.2012.03.025","article-title":"MEK\/ERK pathway mediates insulin-promoted degradation of MKP-3 protein in liver cells","volume":"361","author":"Feng","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E8027","DOI":"10.1073\/pnas.1800076115","article-title":"WDUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation","volume":"115","author":"Hsu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cell.2014.01.009","article-title":"Erk1\/2 activity promotes chromatin features and RNAPII phosphorylation at developmental promoters in mouse ESCs","volume":"156","author":"Tee","year":"2014","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.bbrc.2019.10.081","article-title":"Simple differentiation method using FBS identifies DUSP6 as a marker for fine-tuning of FGF-ERK signaling activity in human pluripotent stem cells","volume":"521","author":"Yoo","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nrn2822","article-title":"New neurons and new memories: How does adult hippocampal neurogenesis affect learning and memory?","volume":"11","author":"Deng","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.neuron.2011.05.010","article-title":"Resolving new memories: A critical look at the dentate gyrus, adult neurogenesis, and pattern separation","volume":"70","author":"Aimone","year":"2011","journal-title":"Neuron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.brainres.2016.03.053","article-title":"Development and application of novel histochemical tracers for localizing brain connectivity and pathology","volume":"1645","author":"Schmued","year":"2016","journal-title":"Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0006-8993(00)02513-0","article-title":"Fluoro-Jade B: A high affinity fluorescent marker for the localization of neuronal degeneration","volume":"874","author":"Schmued","year":"2000","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.brainres.2004.11.054","article-title":"Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons","volume":"1035","author":"Schmued","year":"2005","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jneumeth.2011.11.022","article-title":"Simple model of forebrain ischemia in mouse","volume":"204","author":"Onken","year":"2012","journal-title":"J. Neurosci. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"41882","DOI":"10.1074\/jbc.M406720200","article-title":"Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal","volume":"279","author":"Karlsson","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1038\/jcbfm.2012.32","article-title":"Novel mitochondrial targets for neuroprotection","volume":"32","author":"Stetler","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/jnc.15029","article-title":"Protective effects of ischemic preconditioning against neuronal apoptosis and dendritic injury in the hippocampus are age-dependent","volume":"155","author":"Lee","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.neulet.2006.09.053","article-title":"Ischemic preconditioning-induced activation of ERK1\/2 in the rat hippocampus","volume":"409","author":"Choi","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1097\/00001756-200111160-00023","article-title":"Extracellular signal-regulated kinase and c-Jun N-terminal protein kinase in ischemic tolerance","volume":"12","author":"Gu","year":"2001","journal-title":"Neuroreport"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.neures.2006.01.006","article-title":"The role of extracellular signal-regulated kinases in the neuroprotection of limb ischemic preconditioning","volume":"55","author":"Jin","year":"2006","journal-title":"Neurosci. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12035-013-8436-4","article-title":"Hypoxic preconditioning attenuates neuronal cell death by preventing MEK\/ERK signaling pathway activation after transient global cerebral ischemia in adult rats","volume":"48","author":"Zhan","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.bbadis.2016.01.015","article-title":"Stroke injury, cognitive impairment and vascular dementia","volume":"1862","author":"Kalaria","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1161\/CIRCRESAHA.116.308426","article-title":"Vascular Cognitive Impairment","volume":"120","author":"Dichgans","year":"2017","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0006-8993(01)03371-6","article-title":"Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion","volume":"929","author":"Butler","year":"2002","journal-title":"Brain Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/nchembio.190","article-title":"Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages","volume":"5","author":"Molina","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.semcdb.2016.01.009","article-title":"The regulation of oncogenic Ras\/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs)","volume":"50","author":"Kidger","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.canlet.2017.10.007","article-title":"Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and metastasis and overcomes cisplatin resistance","volume":"412","author":"Wu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"dev157206","DOI":"10.1242\/dev.157206","article-title":"Dusp6 attenuates Ras\/MAPK signaling to limit zebrafish heart regeneration","volume":"145","author":"Missinato","year":"2018","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1002\/cbic.201402000","article-title":"In vivo structure-activity relationship studies support allosteric targeting of a dual specificity phosphatase","volume":"15","author":"Korotchenko","year":"2014","journal-title":"Chembiochem"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kumar, V., Weng, Y.C., Wu, Y.C., Huang, Y.T., and Chou, W.H. (2018). PKCepsilon phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0479-z"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/jnr.24362","article-title":"Genetic inhibition of PKCepsilon attenuates neurodegeneration after global cerebral ischemia in male mice","volume":"97","author":"Kumar","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, G., Weng, Y.C., Chiang, I.C., Huang, Y.T., Liao, Y.C., Chen, Y.C., Kao, C.Y., Liu, Y.L., Lee, T.H., and Chou, W.H. (2020). Neutralization of Lipocalin-2 Diminishes Stroke-Reperfusion Injury. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176253"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e21317","DOI":"10.1096\/fj.202001018R","article-title":"Lipocalin-2 mediates the rejection of neural transplants","volume":"35","author":"Weng","year":"2021","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1111\/jcmm.12538","article-title":"Lipocalin-2 released in response to cerebral ischaemia mediates reperfusion injury in mice","volume":"19","author":"Wang","year":"2015","journal-title":"J. Cell Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1080\/15548627.2018.1509818","article-title":"Mitochondrial dysfunction and mitophagy defect triggered by heterozygous GBA mutations","volume":"15","author":"Li","year":"2019","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bbr.2008.10.029","article-title":"Evaluation of spatial memory of C57BL\/6J and CD1 mice in the Barnes maze, the Multiple T-maze and in the Morris water maze","volume":"198","author":"Patil","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1152\/physrev.1999.79.4.1431","article-title":"Ischemic cell death in brain neurons","volume":"79","author":"Lipton","year":"1999","journal-title":"Physiol. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:21:13Z","timestamp":1760124073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,22]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24097690"],"URL":"https:\/\/doi.org\/10.3390\/ijms24097690","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,22]]}}}