{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T21:00:54Z","timestamp":1794603654475,"version":"4.9.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Gansu Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["21JR7RA453"],"award-info":[{"award-number":["21JR7RA453"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013804","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine &amp; Pharmacotherapy"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.biopha.2026.119002","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T20:57:51Z","timestamp":1768251471000},"page":"119002","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Ampelopsin preserves glutamate homeostasis against cerebral ischemia"],"prefix":"10.1016","volume":"195","author":[{"given":"Zhen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-mei","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-kai","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-xin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.biopha.2026.119002_bib1","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1002\/jnr.24937","article-title":"Therapeutic time windows of compounds against NMDA receptors signaling pathways for ischemic stroke","volume":"99","author":"Huo","year":"2021","journal-title":"J. Neurosci. Res"},{"issue":"10","key":"10.1016\/j.biopha.2026.119002_bib2","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1161\/STROKEAHA.118.022330","article-title":"Focal Cerebral Ischemia and Reperfusion Induce Brain Injury Through \u03b12\u03b4-1-Bound NMDA Receptors","volume":"49","author":"Luo","year":"2018","journal-title":"Stroke"},{"issue":"4","key":"10.1016\/j.biopha.2026.119002_bib3","doi-asserted-by":"crossref","DOI":"10.3892\/ijmm.2021.5019","article-title":"Protective effects of andrographolide against cerebral ischemia\u2011reperfusion injury in mice","volume":"48","author":"Li","year":"2021","journal-title":"Int J. Mol. Med"},{"issue":"2","key":"10.1016\/j.biopha.2026.119002_bib4","first-page":"87","article-title":"Effect of electroacupuncture on neurovascular unit and Wnt\/\u03b2-catenin signaling in rats with cerebral ischemia","volume":"46","author":"Li","year":"2021","journal-title":"Zhen Ci Yan Jiu"},{"issue":"1","key":"10.1016\/j.biopha.2026.119002_bib5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12974-020-01941-y","article-title":"Blocking glycine receptors reduces neuroinflammation and restores neurotransmission in cerebellum through ADAM17-TNFR1-NF-\u03ba\u03b2 pathway","volume":"17","author":"Arenas","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.biopha.2026.119002_bib6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bbi.2020.11.038","article-title":"Glutaminase in microglia: A novel regulator of neuroinflammation","volume":"92","author":"Ding","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.biopha.2026.119002_bib7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3389\/fimmu.2020.00161","article-title":"Glutaminase 1 Regulates Neuroinflammation After Cerebral Ischemia Through Enhancing Microglial Activation and Pro-Inflammatory Exosome Release","volume":"11","author":"Gao","year":"2020","journal-title":"Front Immunol."},{"key":"10.1016\/j.biopha.2026.119002_bib8","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2147\/NDT.S238455","article-title":"The Expression of GLAST and GLT1 in a Transient Cerebral Ischemia Mongolian Gerbil Model","volume":"16","author":"Shen","year":"2020","journal-title":"Neuropsychiatr. Dis. Treat."},{"issue":"21","key":"10.1016\/j.biopha.2026.119002_bib9","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1158\/0008-5472.CAN-20-0600","article-title":"5-Fluorouracil Enhances the Antitumor Activity of the Glutaminase Inhibitor CB-839 against PIK3CA-Mutant Colorectal Cancers","volume":"80","author":"Zhao","year":"2020","journal-title":"Cancer Res"},{"issue":"3","key":"10.1016\/j.biopha.2026.119002_bib10","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1158\/1535-7163.MCT-20-0430","article-title":"The Glutaminase Inhibitor CB-839 (Telaglenastat) Enhances the Antimelanoma Activity of T-Cell-Mediated Immunotherapies","volume":"20","author":"Varghese","year":"2021","journal-title":"Mol. Cancer Ther."},{"issue":"13","key":"10.1016\/j.biopha.2026.119002_bib11","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1158\/0008-5472.CAN-18-3527","article-title":"LKB1 and KEAP1\/NRF2 Pathways Cooperatively Promote Metabolic Reprogramming with Enhanced Glutamine Dependence in KRAS-Mutant Lung Adenocarcinoma","volume":"79","author":"Galan-Cobo","year":"2019","journal-title":"Cancer Res"},{"issue":"4","key":"10.1016\/j.biopha.2026.119002_bib12","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","article-title":"Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer","volume":"13","author":"Gross","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.biopha.2026.119002_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2020.114716","article-title":"Urban airborne PM(2.5)-activated microglia mediate neurotoxicity through glutaminase-containing extracellular vesicles in olfactory bulb","volume":"264","author":"Chen","year":"2020","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.biopha.2026.119002_bib14","first-page":"273","article-title":"Effect of glutaminase inhibition on cancer-induced bone pain","volume":"11","author":"Fazzari","year":"2019","journal-title":"Breast Cancer (Dove Med Press)"},{"issue":"18","key":"10.1016\/j.biopha.2026.119002_bib15","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1158\/1078-0432.CCR-21-1204","article-title":"A Phase I Dose-Escalation and Expansion Study of Telaglenastat in Patients with Advanced or Metastatic Solid Tumors","volume":"27","author":"Harding","year":"2021","journal-title":"Clin. Cancer Res"},{"issue":"7","key":"10.1016\/j.biopha.2026.119002_bib16","article-title":"Control of Reactive Oxygen Species for the Prevention of Parkinson's Disease: The Possible Application of Flavonoids","volume":"9","author":"Kim","year":"2020","journal-title":"Antioxid. (Basel)"},{"key":"10.1016\/j.biopha.2026.119002_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2018.12.136","article-title":"Ampelopsin inhibits human glioma through inducing apoptosis and autophagy dependent on ROS generation and JNK pathway","volume":"116","author":"Guo","year":"2019","journal-title":"Biomed. Pharm."},{"key":"10.1016\/j.biopha.2026.119002_bib18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.intimp.2016.12.018","article-title":"Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-\u03baB and JAK2\/STAT3 signaling pathways in microglia","volume":"44","author":"Weng","year":"2017","journal-title":"Int Immunopharmacol."},{"issue":"12","key":"10.1016\/j.biopha.2026.119002_bib19","doi-asserted-by":"crossref","DOI":"10.3390\/foods14122011","article-title":"Inhibitory Mechanisms of Vine Tea Extract and Dihydromyricetin Against Escherichia coli: A Multidimensional Analysis from Cell Membrane to Protein Synthesis","volume":"14","author":"Ma","year":"2025","journal-title":"Foods"},{"issue":"11","key":"10.1016\/j.biopha.2026.119002_bib20","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25116053","article-title":"Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation","volume":"25","author":"Gujar","year":"2024","journal-title":"Int J. Mol. Sci."},{"issue":"6","key":"10.1016\/j.biopha.2026.119002_bib21","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1007\/s13311-023-01425-w","article-title":"Dihydromyricetin Alleviates Ischemic Brain Injury by Antagonizing Pyroptosis in Rats","volume":"20","author":"Ding","year":"2023","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.biopha.2026.119002_bib22","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.biopha.2017.03.070","article-title":"Ampelopsin attenuates the atrophy of skeletal muscle from d-gal-induced aging rats through activating AMPK\/SIRT1\/PGC-1\u03b1 signaling cascade","volume":"90","author":"Kou","year":"2017","journal-title":"Biomed. Pharm."},{"issue":"10","key":"10.1016\/j.biopha.2026.119002_bib23","doi-asserted-by":"crossref","first-page":"7200","DOI":"10.1007\/s12035-015-9627-y","article-title":"Dihydromyricetin Improves Hypobaric Hypoxia-Induced Memory Impairment via Modulation of SIRT3 Signaling","volume":"53","author":"Liu","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.biopha.2026.119002_bib24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.brainres.2010.09.016","article-title":"Neuroprotective effect of astaxanthin on H(2)O(2)-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo","volume":"1360","author":"Lu","year":"2010","journal-title":"Brain Res"},{"key":"10.1016\/j.biopha.2026.119002_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.113752","article-title":"Dihydromyricetin alleviates methotrexate-induced hepatotoxicity via suppressing the \u200eTLR4\/NF-\u03baB pathway and NLRP3 inflammasome\/caspase 1 axis","volume":"155","author":"Matouk","year":"2022","journal-title":"Biomed. Pharm."},{"issue":"1","key":"10.1016\/j.biopha.2026.119002_bib26","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20180902","article-title":"Protective role of Dihydromyricetin in Alzheimer's disease rat model associated with activating AMPK\/SIRT1 signaling pathway","volume":"39","author":"Sun","year":"2019","journal-title":"Biosci. Rep."},{"issue":"4","key":"10.1016\/j.biopha.2026.119002_bib27","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/neuonc\/noab219","article-title":"Glutamine anaplerosis is required for amino acid biosynthesis in human meningiomas","volume":"24","author":"Ijare","year":"2022","journal-title":"Neuro Oncol."},{"key":"10.1016\/j.biopha.2026.119002_bib28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.exphem.2017.09.007","article-title":"Glutaminase inhibition improves FLT3 inhibitor therapy for acute myeloid leukemia","volume":"58","author":"Gregory","year":"2018","journal-title":"Exp. Hematol."},{"issue":"23","key":"10.1016\/j.biopha.2026.119002_bib29","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1182\/blood.V126.23.3059.3059","article-title":"Phase 1 Study of CB-839, a First-in-Class, Glutaminase Inhibitor in Patients with Multiple Myeloma and Lymphoma","volume":"126","author":"Vogl","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.biopha.2026.119002_bib30","doi-asserted-by":"crossref","first-page":"4723","DOI":"10.12659\/MSM.917213","article-title":"Electroacupuncture Alleviates Ischemic Brain Injury by Inhibiting the miR-223\/NLRP3 Pathway","volume":"25","author":"Sha","year":"2019","journal-title":"Med Sci. Monit."},{"issue":"11","key":"10.1016\/j.biopha.2026.119002_bib31","first-page":"5343","article-title":"Gastrodin improves the neurological score in MCAO rats by inhibiting inflammation and apoptosis, promoting revascularization","volume":"11","author":"Wang","year":"2018","journal-title":"Int J. Clin. Exp. Pathol."},{"issue":"3","key":"10.1016\/j.biopha.2026.119002_bib32","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1161\/01.STR.17.3.472","article-title":"Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination","volume":"17","author":"Bederson","year":"1986","journal-title":"Stroke"},{"issue":"6","key":"10.1016\/j.biopha.2026.119002_bib33","article-title":"Melatonin attenuates brain edema via the PI3K\/Akt\/Nrf2 pathway in rats with cerebral ischemia-reperfusion injury","volume":"34","author":"Liu","year":"2025","journal-title":"J. Stroke Cereb. Dis."},{"issue":"6","key":"10.1016\/j.biopha.2026.119002_bib34","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00018-003-3319-x","article-title":"Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury","volume":"61","author":"Arundine","year":"2004","journal-title":"Cell Mol. Life Sci."},{"issue":"8","key":"10.1016\/j.biopha.2026.119002_bib35","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3109\/00207454.2011.570464","article-title":"Role of glutamine in neuronal survival and death during brain ischemia and hypoglycemia","volume":"121","author":"Stelmashook","year":"2011","journal-title":"Int J. Neurosci."},{"issue":"1","key":"10.1016\/j.biopha.2026.119002_bib36","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0006-8993(95)01372-5","article-title":"M: Glutamate, glutamine and glutamine synthetase in the neonatal rat brain following hypoxia","volume":"707","author":"Krajnc","year":"1996","journal-title":"Brain Res"},{"key":"10.1016\/j.biopha.2026.119002_bib37","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1472100","article-title":"Salidroside ameliorates cerebral ischemic injury and regulates the glutamate metabolism pathway in astrocytes","volume":"15","author":"Zheng","year":"2024","journal-title":"Front Pharm."},{"issue":"4","key":"10.1016\/j.biopha.2026.119002_bib38","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41418-024-01264-y","article-title":"Set7\/9 aggravates ischemic brain injury via enhancing glutamine metabolism in a blocking Sirt5 manner","volume":"31","author":"Wang","year":"2024","journal-title":"Cell Death Differ."},{"issue":"1","key":"10.1016\/j.biopha.2026.119002_bib39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0006-8993(98)01006-3","article-title":"Characterization of mitochondrial glutaminase and amino acids at prolonged times after experimental focal cerebral ischemia","volume":"813","author":"Newcomb","year":"1998","journal-title":"Brain Res"},{"issue":"16","key":"10.1016\/j.biopha.2026.119002_bib40","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22168504","article-title":"Mitochondrial Metabolism behind Region-Specific Resistance to Ischemia-Reperfusion Injury in Gerbil Hippocampus. Role of PKC\u03b2II and Phosphate-Activated Glutaminase","volume":"22","author":"Ber\u0119sewicz-Haller","year":"2021","journal-title":"Int J. Mol. Sci."},{"issue":"9","key":"10.1016\/j.biopha.2026.119002_bib41","doi-asserted-by":"crossref","first-page":"742","DOI":"10.2174\/1568009623666230329123358","article-title":"HDAC4-mediated Deacetylation of Glutaminase Facilitates Glioma Stemness","volume":"23","author":"Xu","year":"2023","journal-title":"Curr. Cancer Drug Targets"},{"issue":"5","key":"10.1016\/j.biopha.2026.119002_bib42","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1189\/jlb.0306153","article-title":"The glutamate-glutamine cycle as an inducible, protective face of macrophage activation","volume":"80","author":"Gras","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.biopha.2026.119002_bib43","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2021.578922","article-title":"Disturbance of the Glutamate-Glutamine Cycle, Secondary to Hepatic Damage, Compromises Memory Function","volume":"15","author":"Lim\u00f3n","year":"2021","journal-title":"Front Neurosci."},{"issue":"2","key":"10.1016\/j.biopha.2026.119002_bib44","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s10072-011-0828-5","article-title":"The role of glutamate in neuronal ischemic injury: the role of spark in fire","volume":"33","author":"Kostandy","year":"2012","journal-title":"Neurol. Sci."},{"issue":"4-5","key":"10.1016\/j.biopha.2026.119002_bib45","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0197-0186(03)00024-X","article-title":"Neurotoxic and neuroprotective effects of the glutamate transporter inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) during physiological and ischemia-like conditions","volume":"43","author":"Bonde","year":"2003","journal-title":"Neurochem. Int"},{"issue":"2","key":"10.1016\/j.biopha.2026.119002_bib46","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s12640-020-00209-w","article-title":"Fluoxetine and Riluzole Mitigates Manganese-Induced Disruption of Glutamate Transporters and Excitotoxicity via Ephrin-A3\/GLAST-GLT-1\/Glu Signaling Pathway in Striatum of Mice","volume":"38","author":"Qi","year":"2020","journal-title":"Neurotox. Res"},{"issue":"1","key":"10.1016\/j.biopha.2026.119002_bib47","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s12035-015-9643-y","article-title":"Sulforaphane Prevents Methylmercury-Induced Oxidative Damage and Excitotoxicity Through Activation of the Nrf2-ARE Pathway","volume":"54","author":"Feng","year":"2017","journal-title":"Mol. Neurobiol."},{"issue":"7","key":"10.1016\/j.biopha.2026.119002_bib48","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1039\/C8MT00056E","article-title":"Conditioned medium from overly excitatory primary astrocytes induced by La(3+) increases apoptosis in primary neurons via upregulating the expression of NMDA receptors","volume":"10","author":"Sun","year":"2018","journal-title":"Metallomics"},{"key":"10.1016\/j.biopha.2026.119002_bib49","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2021.637784","article-title":"Disruption of Glutamate Transport and Homeostasis by Acute Metabolic Stress","volume":"15","author":"Passlick","year":"2021","journal-title":"Front Cell Neurosci."}],"container-title":["Biomedicine &amp; Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S075333222600034X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S075333222600034X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:27:30Z","timestamp":1772810850000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S075333222600034X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":49,"alternative-id":["S075333222600034X"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119002","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ampelopsin preserves glutamate homeostasis against cerebral ischemia","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"119002"}}