{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:22:14Z","timestamp":1792059734287,"version":"4.4.0"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Ischemia-reperfusion (I\/R) injury is a major cause of cell death and organ damage in numerous pathologies, including myocardial infarction, stroke, and acute kidney injury. Current treatment methods for I\/R injury are limited. Ferroptosis, which is a newly uncovered type of regulated cell death characterized by iron overload and lipid peroxidation accumulation, has been investigated in various diseases. There is increasing evidence of a close association between ferroptosis and I\/R injury, with ferroptosis frequently identified as a new therapeutic target for the management of I\/R injury. This review summarizes the current status of ferroptosis and discusses its relationship with I\/R injury, as well as potential treatment strategies targeting it.<\/jats:p>","DOI":"10.3389\/fcell.2021.688605","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T03:55:42Z","timestamp":1628567742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":100,"title":["Ferroptosis: A Novel Therapeutic Target for Ischemia-Reperfusion Injury"],"prefix":"10.3389","volume":"9","author":[{"given":"Yunqing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanmin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlin","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"F702","DOI":"10.1152\/ajprenal.00044.2017","article-title":"Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells.","volume":"314","author":"Adedoyin","year":"2018","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/s41586-019-1705-2","article-title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.","volume":"575","author":"Bersuker","year":"2019","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1161\/circinterventions.111.966226","article-title":"Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction.","volume":"5","author":"Chan","year":"2012","journal-title":"Circ. Cardiovasc. Interv."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.biocel.2006.02.006","article-title":"Heat shock protein 27 downregulates the transferrin receptor 1-mediated iron uptake.","volume":"38","author":"Chen","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.590226","article-title":"Iron metabolism in ferroptosis.","volume":"8","author":"Chen","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-03135-z","article-title":"miR-182-5p and miR-378a-3p regulate ferroptosis in I\/R-induced renal injury.","volume":"11","author":"Ding","year":"2020","journal-title":"Cell Death Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death.","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1021\/acschembio.5b00245","article-title":"Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death.","volume":"10","author":"Dixon","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41586-019-1707-0","article-title":"FSP1 is a glutathione-independent ferroptosis suppressor.","volume":"575","author":"Doll","year":"2019","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition.","volume":"13","author":"Doll","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/s1535-6108(03)00050-3","article-title":"Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.","volume":"3","author":"Dolma","year":"2003","journal-title":"Cancer Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/ncb3053","article-title":"Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo.","volume":"16","author":"Dowdle","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2013from mechanism to translation.","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.628988","article-title":"Baicalin prevents myocardial ischemia\/reperfusion injury through inhibiting ACSL4 mediated ferroptosis.","volume":"12","author":"Fan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1073\/pnas.1821022116","article-title":"Ferroptosis as a target for protection against cardiomyopathy.","volume":"116","author":"Fang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B16","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.bbrc.2019.10.006","article-title":"Liproxstatin-1 protects the mouse myocardium against ischemia\/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels.","volume":"520","author":"Feng","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice.","volume":"16","author":"Friedmann Angeli","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1038\/cr.2016.95","article-title":"Ferroptosis is an autophagic cell death process.","volume":"26","author":"Gao","year":"2016","journal-title":"Cell Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.molcel.2015.06.011","article-title":"Glutaminolysis and transferrin regulate ferroptosis.","volume":"59","author":"Gao","year":"2015","journal-title":"Mol. Cell"},{"key":"B20","first-page":"3826","article-title":"Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma cells.","volume":"22","author":"Geng","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1177\/1074248411409581","article-title":"Cell death pathways in acute ischemia\/reperfusion injury.","volume":"16","author":"Gottlieb","year":"2011","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116795","article-title":"The neuroprotective effects of carvacrol on ischemia\/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation.","volume":"235","author":"Guan","year":"2019","journal-title":"Life Sci."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118660","article-title":"Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11\/GPX4 axis in gerbils.","volume":"264","author":"Guan","year":"2021","journal-title":"Life Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s10557-006-0583-7","article-title":"The interplay between pro-death and pro-survival signaling pathways in myocardial ischemia\/reperfusion injury: apoptosis meets autophagy.","volume":"20","author":"Hamacher-Brady","year":"2006","journal-title":"Cardiovasc. Drugs Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1124\/jpet.108.149807","article-title":"Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke.","volume":"330","author":"Hanson","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"115164","DOI":"10.18632\/oncotarget.23046","article-title":"Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression.","volume":"8","author":"Hong","year":"2017","journal-title":"Oncotarget"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1080\/15548627.2016.1187366","article-title":"Autophagy promotes ferroptosis by degradation of ferritin.","volume":"12","author":"Hou","year":"2016","journal-title":"Autophagy"},{"key":"B28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature14344","article-title":"Ferroptosis as a p53-mediated activity during tumour suppression.","volume":"520","author":"Jiang","year":"2015","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"261","DOI":"10.14336\/ad.2020.0323","article-title":"Mechanism of ferroptosis: a potential target for cardiovascular diseases treatment.","volume":"12","author":"Ju","year":"2021","journal-title":"Aging Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/978-3-7091-9334-1_23","article-title":"Proposed toxic oxidant inhibitors fail to reduce brain edema.","volume":"60","author":"Judy","year":"1994","journal-title":"Acta Neurochir. Suppl. (Wien)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2020.108433","article-title":"Necroptosis in renal ischemia\/reperfusion injury: a major mode of cell death?","volume":"689","author":"Jun","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"B32","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1021\/acscentsci.9b01063","article-title":"GTP cyclohydrolase 1\/tetrahydrobiopterin counteract ferroptosis through lipid remodeling.","volume":"6","author":"Kraft","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"B34","first-page":"6417","article-title":"Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors.","volume":"34","author":"Lachaier","year":"2014","journal-title":"Anticancer Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/00005344-199010000-00002","article-title":"High-dose iron-chelator therapy during reperfusion with deferoxamine-hydroxyethyl starch conjugate fails to reduce canine infarct size.","volume":"16","author":"Lesnefsky","year":"1990","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B36","article-title":"The interaction between ferroptosis and lipid metabolism in cancer.","volume":"5","author":"Li","year":"2020","journal-title":"Signal. Transduct. Target Ther."},{"key":"B37","article-title":"Ferroptosis: past, present and future.","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis."},{"key":"B38","first-page":"3051","article-title":"Ferroptosis is associated with oxygen-glucose deprivation\/reoxygenation-induced Sertoli cell death.","volume":"41","author":"Li","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1172\/jci126428","article-title":"Ferroptotic cell death and TLR4\/Trif signaling initiate neutrophil recruitment after heart transplantation.","volume":"129","author":"Li","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B40","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1089\/dna.2019.5097","article-title":"Ferroptosis is involved in diabetes myocardial ischemia\/reperfusion injury through endoplasmic reticulum stress.","volume":"39","author":"Li","year":"2020","journal-title":"DNA Cell Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1038\/s41418-019-0299-4","article-title":"Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia\/reperfusion.","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death Differ."},{"key":"B42","doi-asserted-by":"publisher","first-page":"16836","DOI":"10.1073\/pnas.1415518111","article-title":"Synchronized renal tubular cell death involves ferroptosis.","volume":"111","author":"Linkermann","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1158\/0008-5472.can-18-3037","article-title":"The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SLC7A11.","volume":"79","author":"Liu","year":"2019","journal-title":"Cancer Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.yjmcc.2004.11.009","article-title":"Ischemia\/reperfusion injury at the intersection with cell death.","volume":"38","author":"Logue","year":"2005","journal-title":"J. Mol. Cell Cardiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy.","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1007\/s00018-017-2547-4","article-title":"Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure.","volume":"74","author":"Muller","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"B47","first-page":"IV328","article-title":"Deferoxamine fails to improve postischemic cardiac function in hypertrophied hearts.","volume":"82","author":"Nakamura","year":"1990","journal-title":"Circulation"},{"key":"B48","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.freeradbiomed.2015.11.013","article-title":"Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy.","volume":"90","author":"Ni","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1517\/14656566.2016.1115015","article-title":"Advances in treatment strategies for ischemia reperfusion injury.","volume":"17","author":"Pantazi","year":"2016","journal-title":"Expert Opin. Pharmacother."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1002\/hep.31328","article-title":"Iron chaperone poly rC binding protein 1 protects mouse liver from lipid peroxidation and steatosis.","volume":"73","author":"Protchenko","year":"2021","journal-title":"Hepatology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"11455","DOI":"10.1074\/jbc.274.17.11455","article-title":"Cloning and expression of a plasma membrane cystine\/glutamate exchange transporter composed of two distinct proteins.","volume":"274","author":"Sato","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B52","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/8880141","article-title":"The protective effect of cyanidin-3-glucoside on myocardial ischemia-reperfusion injury through ferroptosis.","volume":"2021","author":"Shan","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nchembio.2079","article-title":"Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis.","volume":"12","author":"Shimada","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease.","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"5617","DOI":"10.1038\/onc.2015.32","article-title":"HSPB1 as a novel regulator of ferroptotic cancer cell death.","volume":"34","author":"Sun","year":"2015","journal-title":"Oncogene"},{"key":"B56","doi-asserted-by":"publisher","first-page":"497","DOI":"10.2174\/1568026013394741","article-title":"Oxytosis: a novel form of programmed cell death.","volume":"1","author":"Tan","year":"2001","journal-title":"Curr. Top Med. Chem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5355","DOI":"10.1158\/0008-5472.can-19-0369","article-title":"Stearoyl-CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death.","volume":"79","author":"Tesfay","year":"2019","journal-title":"Cancer Res."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.173999","article-title":"Combination of ponatinib with deferoxamine synergistically mitigates ischemic heart injury via simultaneous prevention of necroptosis and ferroptosis.","volume":"898","author":"Tu","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1038\/mp.2017.171","article-title":"Tau-mediated iron export prevents ferroptotic damage after ischemic stroke.","volume":"22","author":"Tuo","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"B60","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.jare.2020.07.007","article-title":"Quercetin alleviates acute kidney injury by inhibiting ferroptosis.","volume":"28","author":"Wang","year":"2021","journal-title":"J. Adv. Res."},{"key":"B61","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.cell.2017.09.044","article-title":"PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals.","volume":"171","author":"Wenzel","year":"2017","journal-title":"Cell"},{"key":"B62","doi-asserted-by":"publisher","first-page":"16262","DOI":"10.1096\/fj.202001758r","article-title":"Inhibition of ACSL4 attenuates ferroptotic damage after pulmonary ischemia-reperfusion.","volume":"34","author":"Xu","year":"2020","journal-title":"FASEB J."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1111\/ajt.15773","article-title":"Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: potential role of ferroptosis.","volume":"20","author":"Yamada","year":"2020","journal-title":"Am. J. Transplant."},{"key":"B64","article-title":"Ferroptosis: mechanisms and links with diseases.","volume":"6","author":"Yan","year":"2021","journal-title":"Signal. Transduct. Target Ther."},{"key":"B65","doi-asserted-by":"crossref","first-page":"E4966","DOI":"10.1073\/pnas.1603244113","article-title":"Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis.","volume":"113","author":"Yang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B66","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4.","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","article-title":"Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells.","volume":"15","author":"Yang","year":"2008","journal-title":"Chem. Biol."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/biom11070923","article-title":"Kaempferol ameliorates oxygen-glucose deprivation\/reoxygenation-induced neuronal ferroptosis by activating Nrf2\/SLC7A11\/GPX4 axis.","volume":"11","author":"Yuan","year":"2021","journal-title":"Biomolecules"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.2147\/ijn.s43263","article-title":"Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro.","volume":"8","author":"Zhang","year":"2013","journal-title":"Int. J. Nanomedicine"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/s41556-018-0178-0","article-title":"BAP1 links metabolic regulation of ferroptosis to tumour suppression.","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat. Cell. Biol."},{"key":"B71","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-02871-6","article-title":"XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia-reperfusion injury.","volume":"11","author":"Zhao","year":"2020","journal-title":"Cell Death Dis."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.688605\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T03:55:55Z","timestamp":1628567755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.688605\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,10]]},"references-count":71,"alternative-id":["10.3389\/fcell.2021.688605"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.688605","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,10]]},"article-number":"688605"}}