{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:40:50Z","timestamp":1790019650067,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82027802"],"award-info":[{"award-number":["82027802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100925"],"award-info":[{"award-number":["32100925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Z211100002121038"],"award-info":[{"award-number":["Z211100002121038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019A36"],"award-info":[{"award-number":["2019A36"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["303-01-005-0019"],"award-info":[{"award-number":["303-01-005-0019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82027802"],"award-info":[{"award-number":["82027802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100925"],"award-info":[{"award-number":["32100925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Z211100002121038"],"award-info":[{"award-number":["Z211100002121038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019A36"],"award-info":[{"award-number":["2019A36"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["303-01-005-0019"],"award-info":[{"award-number":["303-01-005-0019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["82027802"],"award-info":[{"award-number":["82027802"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["32100925"],"award-info":[{"award-number":["32100925"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["Z211100002121038"],"award-info":[{"award-number":["Z211100002121038"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["2019A36"],"award-info":[{"award-number":["2019A36"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["303-01-005-0019"],"award-info":[{"award-number":["303-01-005-0019"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Hundred Thousand and Ten Thousand Talent Project","award":["82027802"],"award-info":[{"award-number":["82027802"]}]},{"name":"Beijing Hundred Thousand and Ten Thousand Talent Project","award":["32100925"],"award-info":[{"award-number":["32100925"]}]},{"name":"Beijing Hundred Thousand and Ten Thousand Talent Project","award":["Z211100002121038"],"award-info":[{"award-number":["Z211100002121038"]}]},{"name":"Beijing Hundred Thousand and Ten Thousand Talent Project","award":["2019A36"],"award-info":[{"award-number":["2019A36"]}]},{"name":"Beijing Hundred Thousand and Ten Thousand Talent Project","award":["303-01-005-0019"],"award-info":[{"award-number":["303-01-005-0019"]}]},{"name":"Beijing Municipal Health Commission","award":["82027802"],"award-info":[{"award-number":["82027802"]}]},{"name":"Beijing Municipal Health Commission","award":["32100925"],"award-info":[{"award-number":["32100925"]}]},{"name":"Beijing Municipal Health Commission","award":["Z211100002121038"],"award-info":[{"award-number":["Z211100002121038"]}]},{"name":"Beijing Municipal Health Commission","award":["2019A36"],"award-info":[{"award-number":["2019A36"]}]},{"name":"Beijing Municipal Health Commission","award":["303-01-005-0019"],"award-info":[{"award-number":["303-01-005-0019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxic stress occurs in various physiological and pathological states, such as aging, disease, or high-altitude exposure, all of which pose a challenge to many organs in the body, necessitating adaptation. However, the exact mechanisms by which hypoxia affects advanced brain function (learning and memory skills in particular) remain unclear. In this study, we investigated the effects of hypoxic stress on hippocampal function. Specifically, we studied the effects of the dysfunction of mitochondrial oxidative phosphorylation using global proteomics. First, we found that hypoxic stress impaired cognitive and motor abilities, whereas it caused no substantial changes in the brain morphology or structure of mice. Second, bioinformatics analysis indicated that hypoxia affected the expression of 516 proteins, of which 71.1% were upregulated and 28.5% were downregulated. We demonstrated that mitochondrial function was altered and manifested as a decrease in NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 expression, accompanied by increased reactive oxygen species generation, resulting in further neuronal injury. These results may provide some new insights into how hypoxic stress alters hippocampal function via the dysfunction of mitochondrial oxidative phosphorylation.<\/jats:p>","DOI":"10.3390\/ijms232214094","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:24:53Z","timestamp":1668565493000},"page":"14094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Proteomic Analysis Reveals That Mitochondria Dominate the Hippocampal Hypoxic Response in Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Qianqian","family":"Shao","sequence":"first","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaifen","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"},{"name":"Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Gu","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Guan","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"},{"name":"Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengming","family":"Tian","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[{"name":"Laboratory of Brain Disorders, Beijing Institute of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China"},{"name":"Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1164\/rccm.202105-1274OC","article-title":"Sleep Apnea-Specific Hypoxic Burden, Symptom Subtypes, and Risk of Cardiovascular Events and All-Cause Mortality","volume":"205","author":"Trzepizur","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kaczynska, K., Orlowska, M.E., and Andrzejewski, K. (2022). Respiratory Abnormalities in Parkinson\u2019s Disease: What Do We Know from Studies in Humans and Animal Models?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073499"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.biopsych.2021.02.973","article-title":"Chronic Intermittent Hypoxia Enhances Pathological Tau Seeding, Propagation, and Accumulation and Exacerbates Alzheimer-like Memory and Synaptic Plasticity Deficits and Molecular Signatures","volume":"91","author":"Kazim","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1111\/jce.14985","article-title":"Ventricular activation pattern assessment during right ventricular pacing: Ultra-high-frequency ECG study","volume":"32","author":"Curila","year":"2021","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S1474-4422(09)70014-6","article-title":"The cerebral effects of ascent to high altitudes","volume":"8","author":"Wilson","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.physbeh.2014.11.033","article-title":"Ascent to moderate altitude impairs overnight memory improvements","volume":"139","author":"Tesler","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_7","first-page":"411","article-title":"Multi-domain cognitive screening test for neuropsychological assessment for cognitive decline in acclimatized lowlanders staying at high altitude","volume":"136","author":"Hota","year":"2012","journal-title":"Indian J. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20712","DOI":"10.1074\/jbc.R115.662627","article-title":"Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases","volume":"290","author":"Markolovic","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41580-020-0227-y","article-title":"Cellular adaptation to hypoxia through hypoxia inducible factors and beyond","volume":"21","author":"Lee","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7189","DOI":"10.1074\/jbc.M116.774471","article-title":"Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements","volume":"292","author":"Mookerjee","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cmet.2006.01.012","article-title":"HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption","volume":"3","author":"Papandreou","year":"2006","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"806650","DOI":"10.3389\/fmolb.2021.806650","article-title":"Accumulated ROS Activates HIF-1alpha-Induced Glycolysis and Exerts a Protective Effect on Sensory Hair Cells Against Noise-Induced Damage","volume":"8","author":"Liang","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ng.2007.62","article-title":"Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism","volume":"40","author":"Aragones","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41590-020-00834-9","article-title":"Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion","volume":"22","author":"Scharping","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41580-021-00415-0","article-title":"The assembly, regulation and function of the mitochondrial respiratory chain","volume":"23","author":"Vercellino","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.mito.2020.10.004","article-title":"Complex IV\u2014The regulatory center of mitochondrial oxidative phosphorylation","volume":"58","author":"Kadenbach","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: Relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41380-021-01172-4","article-title":"A Baldwin interpretation of adult hippocampal neurogenesis: From functional relevance to physiopathology","volume":"27","author":"Abrous","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/s41422-018-0071-1","article-title":"Structure of the intact 14-subunit human cytochrome c oxidase","volume":"28","author":"Zong","year":"2018","journal-title":"Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.aad9642","article-title":"Hypoxia as a therapy for mitochondrial disease","volume":"352","author":"Jain","year":"2016","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.cmet.2011.10.008","article-title":"Induction of the mitochondrial NDUFA4L2 protein by HIF-1alpha decreases oxygen consumption by inhibiting Complex I activity","volume":"14","author":"Tello","year":"2011","journal-title":"Cell Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2008.04.009","article-title":"Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway","volume":"30","author":"Kaelin","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cmet.2006.02.002","article-title":"HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia","volume":"3","author":"Kim","year":"2006","journal-title":"Cell Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2007.01.047","article-title":"HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells","volume":"129","author":"Fukuda","year":"2007","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1073\/pnas.1419767112","article-title":"Higd1a is a positive regulator of cytochrome c oxidase","volume":"112","author":"Hayashi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00109-020-01905-y","article-title":"Stress-mediated generation of deleterious ROS in healthy individuals\u2014Role of cytochrome c oxidase","volume":"98","author":"Ramzan","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1158\/1078-0432.CCR-15-1987","article-title":"NDUFA4L2 Fine-tunes Oxidative Stress in Hepatocellular Carcinoma","volume":"22","author":"Lai","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1126\/science.abi7495","article-title":"Fumarate is a terminal electron acceptor in the mammalian electron transport chain","volume":"374","author":"Spinelli","year":"2021","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1021\/cr500266a","article-title":"Reaction mechanism of cytochrome c oxidase","volume":"115","author":"Yoshikawa","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ramzan, R., Dolga, A.M., Michels, S., Weber, P., Culmsee, C., Rastan, A.J., and Vogt, S. (2022). Cytochrome c Oxidase Inhibition by ATP Decreases Mitochondrial ROS Production. Cells, 11.","DOI":"10.3390\/cells11060992"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.tem.2018.03.009","article-title":"NDUFA4 (Renamed COXFA4) Is a Cytochrome-c Oxidase Subunit","volume":"29","author":"Pitceathly","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eabl5182","DOI":"10.1126\/sciadv.abl5182","article-title":"Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48","volume":"7","author":"Clayton","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E251","DOI":"10.1111\/ans.13617","article-title":"Overexpression of NDUFA4L2 is associated with poor prognosis in patients with colorectal cancer","volume":"87","author":"Lv","year":"2017","journal-title":"ANZ J. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1111\/1759-7714.12984","article-title":"Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress","volume":"10","author":"Meng","year":"2019","journal-title":"Thorac. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41586-020-2288-7","article-title":"C9orf72 suppresses systemic and neural inflammation induced by gut bacteria","volume":"582","author":"Burberry","year":"2020","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lfs.2018.09.031","article-title":"HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB\/c mice","volume":"212","author":"Rezaee","year":"2018","journal-title":"Life Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14094\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:32Z","timestamp":1760145512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,15]]},"references-count":37,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214094"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214094","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,15]]}}}