{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T21:33:47Z","timestamp":1783719227215,"version":"3.55.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Pharmacol Sin"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1038\/s41401-025-01604-9","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T02:00:46Z","timestamp":1751248846000},"page":"3204-3216","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PYRCR alleviates myocardial ischemia\/reperfusion injury in mice via inhibiting DRG2-mediated cardiomyocyte pyroptosis"],"prefix":"10.1038","volume":"46","author":[{"given":"Xin-zhe","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-fei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-mei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-hai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-hao","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-qin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-qian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"1604_CR1","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.jacc.2022.05.033","volume":"80","author":"R Mohebi","year":"2022","unstructured":"Mohebi R, Chen C, Ibrahim NE, McCarthy CP, Gaggin HK, Singer DE, et al. Cardiovascular disease projections in the United States based on the 2020 census estimates. J Am Coll Cardiol. 2022;80:565\u201378.","journal-title":"J Am Coll Cardiol"},{"key":"1604_CR2","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1016\/j.cardfail.2023.07.006","volume":"29","author":"B Bozkurt","year":"2023","unstructured":"Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, et al. Heart failure epidemiology and outcomes statistics: a report of the heart failure society of America. J Card Fail. 2023;29:1412\u201351.","journal-title":"J Card Fail"},{"key":"1604_CR3","doi-asserted-by":"publisher","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","volume":"143","author":"SS Virani","year":"2021","unstructured":"Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143:e254\u2013e743.","journal-title":"Circulation"},{"key":"1604_CR4","doi-asserted-by":"crossref","unstructured":"Sabolov\u00e1 G, Ko\u010dan L, Rabajdov\u00e1 M, Rap\u010danov\u00e1 S, Va\u0161kov\u00e1 J. Association of inflammation, oxidative stress, and deteriorated cognitive functions in patients after cardiac surgery. Vessel Plus. 2024;8:27.","DOI":"10.20517\/2574-1209.2024.05"},{"key":"1604_CR5","first-page":"31","volume":"8","author":"M Botros","year":"2024","unstructured":"Botros M, Fadah K, Mukherjee D. The role of inflammatory response in the development of atherosclerosis, myocardial infarction, and remodeling. Vessel. 2024;8:31.","journal-title":"Vessel"},{"key":"1604_CR6","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13541","volume":"231","author":"L Ying","year":"2021","unstructured":"Ying L, Benjanuwattra J, Chattipakorn SC, Chattipakorn N. The role of RIPK3-regulated cell death pathways and necroptosis in the pathogenesis of cardiac ischaemia-reperfusion injury. Acta Physiol. 2021;231:e13541.","journal-title":"Acta Physiol"},{"key":"1604_CR7","doi-asserted-by":"publisher","first-page":"261","DOI":"10.14336\/AD.2020.0323","volume":"12","author":"J Ju","year":"2021","unstructured":"Ju J, Song YN, Wang K. Mechanism of ferroptosis: a potential target for cardiovascular diseases treatment. Aging Dis. 2021;12:261\u201376.","journal-title":"Aging Dis"},{"key":"1604_CR8","first-page":"e934255","volume":"28","author":"S Shen","year":"2022","unstructured":"Shen S, Wang Z, Sun H, Ma L. Role of NLRP3 inflammasome in myocardial ischemia-reperfusion injury and ventricular remodeling. Med Sci Monit. 2022;28:e934255.","journal-title":"Med Sci Monit"},{"key":"1604_CR9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/S0966-842X(00)01936-3","volume":"9","author":"BT Cookson","year":"2001","unstructured":"Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9:113\u20134.","journal-title":"Trends Microbiol"},{"key":"1604_CR10","doi-asserted-by":"publisher","first-page":"R568","DOI":"10.1016\/j.cub.2016.02.019","volume":"26","author":"L Vande Walle","year":"2016","unstructured":"Vande Walle L, Lamkanfi M. Pyroptosis. Current Biol CB. 2016;26:R568\u2013r72.","journal-title":"Current Biol CB"},{"key":"1604_CR11","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/sj.cdd.4400989","volume":"9","author":"M Lamkanfi","year":"2002","unstructured":"Lamkanfi M, Declercq W, Kalai M, Saelens X, Vandenabeele P. Alice in caspase land. A phylogenetic analysis of caspases from worm to man. Cell Death Differ. 2002;9:358\u201361.","journal-title":"Cell Death Differ."},{"key":"1604_CR12","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/nature15541","volume":"526","author":"N Kayagaki","year":"2015","unstructured":"Kayagaki N, Stowe IB, Lee BL, O\u2019Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526:666\u201371.","journal-title":"Nature"},{"key":"1604_CR13","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1002\/eji.201545523","volume":"45","author":"JL Schmid-Burgk","year":"2015","unstructured":"Schmid-Burgk JL, Gaidt MM, Schmidt T, Ebert TS, Bartok E, Hornung V. Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells. Eur J Immunol. 2015;45:2911\u20137.","journal-title":"Eur J Immunol."},{"key":"1604_CR14","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nature15514","volume":"526","author":"J Shi","year":"2015","unstructured":"Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660\u20135.","journal-title":"Nature"},{"key":"1604_CR15","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.1073\/pnas.73.11.3852","volume":"73","author":"HL Sanger","year":"1976","unstructured":"Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA. 1976;73:3852\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1604_CR16","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/280339a0","volume":"280","author":"MT Hsu","year":"1979","unstructured":"Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 1979;280:339\u201340.","journal-title":"Nature"},{"key":"1604_CR17","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/301578a0","volume":"301","author":"AJ Zaug","year":"1983","unstructured":"Zaug AJ, Grabowski PJ, Cech TR. Autocatalytic cyclization of an excised intervening sequence RNA is a cleavage-ligation reaction. Nature. 1983;301:578\u201383.","journal-title":"Nature"},{"key":"1604_CR18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.omtn.2022.11.022","volume":"31","author":"SL Mehta","year":"2023","unstructured":"Mehta SL, Chokkalla AK, Bathula S, Arruri V, Chelluboina B, Vemuganti R. CDR1as regulates \u03b1-synuclein-mediated ischemic brain damage by controlling miR-7 availability. Mol Ther Nucleic Acids. 2023;31:57\u201367.","journal-title":"Mol Ther Nucleic Acids."},{"key":"1604_CR19","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1080\/15476286.2017.1279788","volume":"14","author":"K Abdelmohsen","year":"2017","unstructured":"Abdelmohsen K, Panda AC, Munk R, Grammatikakis I, Dudekula DB, De S, et al. Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol. 2017;14:361\u20139.","journal-title":"RNA Biol"},{"key":"1604_CR20","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100836","volume":"38","author":"IL Patop","year":"2019","unstructured":"Patop IL, W\u00fcst S, Kadener S. Past, present, and future of circRNAs. EMBO J. 2019;38:e100836.","journal-title":"EMBO J"},{"key":"1604_CR21","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41576-019-0158-7","volume":"20","author":"LS Kristensen","year":"2019","unstructured":"Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20:675\u201391.","journal-title":"Nat Rev Genet."},{"key":"1604_CR22","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.1093\/eurheartj\/ehv713","volume":"37","author":"K Wang","year":"2016","unstructured":"Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016;37:2602\u201311.","journal-title":"Eur Heart J."},{"key":"1604_CR23","doi-asserted-by":"publisher","first-page":"3842","DOI":"10.7150\/thno.19764","volume":"7","author":"Y Zeng","year":"2017","unstructured":"Zeng Y, Du WW, Wu Y, Yang Z, Awan FM, Li X, et al. A circular RNA binds to and activates AKT phosphorylation and nuclear localization reducing apoptosis and enhancing cardiac repair. Theranostics. 2017;7:3842\u201355.","journal-title":"Theranostics"},{"key":"1604_CR24","first-page":"1402","volume":"38","author":"WW Du","year":"2017","unstructured":"Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, et al. Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J. 2017;38:1402\u201312.","journal-title":"Eur Heart J."},{"key":"1604_CR25","doi-asserted-by":"publisher","first-page":"25447","DOI":"10.1016\/S0021-9258(18)47271-7","volume":"269","author":"T Schenker","year":"1994","unstructured":"Schenker T, Lach C, Kessler B, Calderara S, Trueb B. A novel GTP-binding protein which is selectively repressed in SV40 transformed fibroblasts. J Biol Chem. 1994;269:25447\u201353.","journal-title":"J Biol Chem"},{"key":"1604_CR26","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/S0167-4781(00)00025-7","volume":"1491","author":"B Li","year":"2000","unstructured":"Li B, Trueb B. DRG represents a family of two closely related GTP-binding proteins. Biochim Biophys Acta. 2000;1491:196\u2013204.","journal-title":"Biochim Biophys Acta"},{"key":"1604_CR27","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1016\/j.bbamcr.2019.06.003","volume":"1866","author":"M Mani","year":"2019","unstructured":"Mani M, Thao DT, Kim BC, Lee UH, Kim DJ, Jang SH, et al. DRG2 knockdown induces Golgi fragmentation via GSK3\u03b2 phosphorylation and microtubule stabilization. Biochim Biophys Acta Mol Cell Res. 2019;1866:1463\u201374.","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"1604_CR28","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1016\/j.bbrc.2017.03.154","volume":"486","author":"MT Vo","year":"2017","unstructured":"Vo MT, Ko MS, Lee UH, Yoon EH, Lee BJ, Cho WJ, et al. Developmentally regulated GTP-binding protein 2 depletion leads to mitochondrial dysfunction through downregulation of dynamin-related protein 1. Biochem Biophys Res Commun. 2017;486:1014\u201320.","journal-title":"Biochem Biophys Res Commun"},{"key":"1604_CR29","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.bbrc.2017.08.110","volume":"493","author":"M Mani","year":"2017","unstructured":"Mani M, Lee UH, Yoon NA, Yoon EH, Lee BJ, Cho WJ, et al. Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules. Biochem Biophys Res Commun. 2017;493:758\u201364.","journal-title":"Biochem Biophys Res Commun"},{"key":"1604_CR30","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1111\/febs.15125","volume":"287","author":"NA Yoon","year":"2020","unstructured":"Yoon NA, Jung SJ, Choi SH, Ryu JH, Mani M, Lee UH, et al. DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF-A expression. FEBS J. 2020;287:2070\u201386.","journal-title":"FEBS J"},{"key":"1604_CR31","doi-asserted-by":"crossref","unstructured":"Lim HR, Vo MT, Kim DJ, Lee UH, Yoon JH, Kim HJ, et al. DRG2 deficient mice exhibit impaired motor behaviors with reduced striatal dopamine release. Int J Mol Sci. 2019;21:60.","DOI":"10.3390\/ijms21010060"},{"key":"1604_CR32","doi-asserted-by":"crossref","unstructured":"Le AN, Park SS, Le MX, Lee UH, Ko BK, Lim HR, et al. DRG2 depletion promotes endothelial cell senescence and vascular endothelial dysfunction. Int J Mol Sci. 2022;23:2877.","DOI":"10.3390\/ijms23052877"},{"key":"1604_CR33","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0461-1","volume":"110","author":"GJ Lee","year":"2015","unstructured":"Lee GJ, Yan L, Vatner DE, Vatner SF. Mst1 inhibition rescues beta1-adrenergic cardiomyopathy by reducing myocyte necrosis and non-myocyte apoptosis rather than myocyte apoptosis. Basic Res Cardiol. 2015;110:7.","journal-title":"Basic Res Cardiol"},{"key":"1604_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103244","volume":"75","author":"Y Duan","year":"2024","unstructured":"Duan Y, Li Q, Wu J, Zhou C, Liu X, Yue J, et al. A detrimental role of endothelial S1PR2 in cardiac ischemia-reperfusion injury via modulating mitochondrial dysfunction, NLRP3 inflammasome activation, and pyroptosis. Redox Biol. 2024;75:103244.","journal-title":"Redox Biol"},{"key":"1604_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101523","volume":"34","author":"C Zeng","year":"2020","unstructured":"Zeng C, Duan F, Hu J, Luo B, Huang B, Lou X, et al. NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy. Redox Biol. 2020;34:101523.","journal-title":"Redox Biol"},{"key":"1604_CR36","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41419-024-06511-1","volume":"15","author":"YW Guo","year":"2024","unstructured":"Guo YW, Zhu L, Duan YT, Hu YQ, Li LB, Fan WJ, et al. Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission. Cell Death Dis. 2024;15:125.","journal-title":"Cell Death Dis"},{"key":"1604_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110922","volume":"391","author":"B Yang","year":"2024","unstructured":"Yang B, Wang J, Qiao J, Zhang Q, Liu Q, Tan Y, et al. Circ DENND4C inhibits pyroptosis and alleviates ischemia-reperfusion acute kidney injury by exosomes secreted from human urine-derived stem cells. Chem Biol Interact. 2024;391:110922.","journal-title":"Chem Biol Interact."},{"key":"1604_CR38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1095457","volume":"14","author":"D Yang","year":"2023","unstructured":"Yang D, Zhao D, Ji J, Wang C, Liu N, Bao X, et al. CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression. Front Immunol. 2023;14:1095457.","journal-title":"Front Immunol"},{"key":"1604_CR39","doi-asserted-by":"publisher","first-page":"2186319","DOI":"10.1080\/10641963.2023.2186319","volume":"45","author":"S Xu","year":"2023","unstructured":"Xu S, Ge Y, Wang X, Yin W, Zhu X, Wang J, et al. Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis. Clin Exp Hypertens. 2023;45:2186319.","journal-title":"Clin Exp Hypertens"},{"key":"1604_CR40","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41392-022-01306-2","volume":"8","author":"Q Yuan","year":"2023","unstructured":"Yuan Q, Sun Y, Yang F, Yan D, Shen M, Jin Z, et al. CircRNA DICAR as a novel endogenous regulator for diabetic cardiomyopathy and diabetic pyroptosis of cardiomyocytes. Sig Transduct Target Ther. 2023;8:99.","journal-title":"Sig Transduct Target Ther"},{"key":"1604_CR41","doi-asserted-by":"publisher","first-page":"505","DOI":"10.3892\/mmr.2015.4565","volume":"13","author":"C Xu","year":"2016","unstructured":"Xu C, Li H, Zhang L, Jia T, Duan L, Lu C. MicroRNA\u20111915\u20113p prevents the apoptosis of lung cancer cells by downregulating DRG2 and PBX2. Mol Med Rep. 2016;13:505\u201312.","journal-title":"Mol Med Rep"},{"key":"1604_CR42","doi-asserted-by":"publisher","first-page":"485","DOI":"10.4111\/icu.20200574","volume":"62","author":"SC Kim","year":"2021","unstructured":"Kim SC, Lee WH, Kim SH, Abdulkhayevich AA, Park JW, Kim YM, et al. Developmentally regulated GTP-binding protein 2 levels in prostate cancer cell lines impact docetaxel-induced apoptosis. Investig Clin Urol. 2021;62:485\u201395.","journal-title":"Investig Clin Urol."},{"key":"1604_CR43","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41569-022-00703-y","volume":"19","author":"JM Quiles","year":"2022","unstructured":"Quiles JM, Gustafsson \u00c5B. The role of mitochondrial fission in cardiovascular health and disease. Nat Rev Cardiol. 2022;19:723\u201336.","journal-title":"Nat Rev Cardiol"}],"container-title":["Acta Pharmacologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41401-025-01604-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-025-01604-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-025-01604-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:16:52Z","timestamp":1764181012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41401-025-01604-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1604"],"URL":"https:\/\/doi.org\/10.1038\/s41401-025-01604-9","relation":{},"ISSN":["1671-4083","1745-7254"],"issn-type":[{"value":"1671-4083","type":"print"},{"value":"1745-7254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]},"assertion":[{"value":"4 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All the animal studies conformed to Directive 2010\/63\/EU of the European Parliament and were approved by the Biomedical Research Ethics Committee of Qingdao University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}