{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:01:28Z","timestamp":1790283688672,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H280010"],"award-info":[{"award-number":["LY21H280010"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2021KY136"],"award-info":[{"award-number":["2021KY136"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","doi-asserted-by":"publisher","award":["WJW2022007"],"award-info":[{"award-number":["WJW2022007"]}],"id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1007\/s12035-024-04088-6","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T15:01:38Z","timestamp":1709737298000},"page":"7950-7967","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Andrographolide Improves ApoE4-Mediated Blood\u2013Brain Barrier Injury by Alleviating Inflammation"],"prefix":"10.1007","volume":"61","author":[{"given":"Xuebin","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9246-6112","authenticated-orcid":false,"given":"Qin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"issue":"2","key":"4088_CR1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1001\/archpsyc.63.2.168","volume":"63","author":"M Gatz","year":"2006","unstructured":"Gatz M, Reynolds C, Fratiglioni L, Johansson B, Mortimer J, Berg S, Fiske A, Pedersen N (2006) Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry 63(2):168\u2013174","journal-title":"Arch Gen Psychiatry"},{"issue":"1","key":"4088_CR2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1159\/000321984","volume":"31","author":"S Crean","year":"2011","unstructured":"Crean S, Ward A, Mercaldi CJ, Collins JM, Cook MN, Baker NL, Arrighi HM (2011) Apolipoprotein E & #949;4 Prevalence in Alzheimer\u2019s disease patients varies across global populations: a systematic literature review and meta-analysis. Dement Geriatr Cogn Disord 31(1):20\u201330","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"3","key":"4088_CR3","doi-asserted-by":"publisher","first-page":"699","DOI":"10.3233\/JAD-2012-121060","volume":"32","author":"RD Bell","year":"2012","unstructured":"Bell RD (2012) The imbalance of vascular molecules in Alzheimer\u2019s disease. J Alzheimers Dis 32(3):699\u2013709","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"4088_CR4","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","volume":"36","author":"MR Halliday","year":"2016","unstructured":"Halliday MR, Rege SV, Ma Q, Zhao Z, Miller CA, Winkler EA, Zlokovic BV (2016) Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer\u2019s disease. J Cereb Blood Flow Metab 36(1):216\u2013227","journal-title":"J Cereb Blood Flow Metab"},{"issue":"10","key":"4088_CR5","doi-asserted-by":"publisher","first-page":"3582","DOI":"10.1093\/brain\/awab478","volume":"145","author":"RJ Jackson","year":"2022","unstructured":"Jackson RJ, Meltzer JC, Nguyen H, Commins C, Bennett RE, Hudry E, Hyman BT (2022) APOE4 derived from astrocytes leads to blood-brain barrier impairment. Brain 145(10):3582\u20133593","journal-title":"Brain"},{"issue":"2","key":"4088_CR6","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.pathol.2018.11.002","volume":"51","author":"AD Marais","year":"2019","unstructured":"Marais AD (2019) Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease. Pathology 51(2):165\u2013176","journal-title":"Pathology"},{"key":"4088_CR7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.neurobiolaging.2020.06.018","volume":"95","author":"C Ringland","year":"2020","unstructured":"Ringland C, Schweig JE, Paris D, Shackleton B, Lynch CE, Eisenbaum M, Mullan M, Crawford F et al (2020) Apolipoprotein E isoforms differentially regulate matrix metallopeptidase 9 function in Alzheimer\u2019s disease. Neurobiol Aging 95:56\u201368","journal-title":"Neurobiol Aging"},{"issue":"6","key":"4088_CR8","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/s41591-020-0886-4","volume":"26","author":"JW Blanchard","year":"2020","unstructured":"Blanchard JW, Bula M, Davila-Velderrain J, Akay LA, Zhu L, Frank A, Victor MB, Bonner JM et al (2020) Reconstruction of the human blood-brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes. Nat Med 26(6):952\u2013963","journal-title":"Nat Med"},{"issue":"2","key":"4088_CR9","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","volume":"25","author":"DA Nation","year":"2019","unstructured":"Nation DA, Sweeney MD, Montagne A, Sagare AP, D\u2019Orazio LM, Pachicano M, Sepehrband F, Nelson AR et al (2019) Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med 25(2):270\u2013276","journal-title":"Nat Med"},{"key":"4088_CR10","doi-asserted-by":"publisher","first-page":"734001","DOI":"10.3389\/fnins.2021.734001","volume":"15","author":"SC Konings","year":"2021","unstructured":"Konings SC, Torres-Garcia L, Martinsson I, Gouras GK (2021) Astrocytic and neuronal Apolipoprotein E isoforms differentially affect neuronal excitability. Front Neurosci 15:734001","journal-title":"Front Neurosci"},{"issue":"20","key":"4088_CR11","doi-asserted-by":"publisher","first-page":"17536","DOI":"10.1074\/jbc.M111.225532","volume":"286","author":"K Nishitsuji","year":"2011","unstructured":"Nishitsuji K, Hosono T, Nakamura T, Bu G, Michikawa M (2011) Apolipoprotein E regulates the integrity of tight junctions in an isoform-dependent manner in an in vitro blood-brain barrier model. J Biol Chem 286(20):17536\u201317542","journal-title":"J Biol Chem"},{"issue":"2","key":"4088_CR12","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/aps.2009.205","volume":"31","author":"W Wang","year":"2010","unstructured":"Wang W, Wang J, Dong SF, Liu CH, Italiani P, Sun SH, Xu J, Boraschi D et al (2010) Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response. Acta Pharmacol Sin 31(2):191\u2013201","journal-title":"Acta Pharmacol Sin"},{"key":"4088_CR13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.bcp.2017.03.024","volume":"139","author":"WSD Tan","year":"2017","unstructured":"Tan WSD, Liao W, Zhou S, Wong WSF (2017) Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action. Biochem Pharmacol 139:71\u201381","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"4088_CR14","doi-asserted-by":"publisher","first-page":"22904","DOI":"10.1038\/s41598-021-01977-x","volume":"11","author":"SB Arredondo","year":"2021","unstructured":"Arredondo SB, Reyes DT, Herrera-Soto A, Mardones MD, Inestrosa NC, Varela-Nallar L (2021) Andrographolide promotes hippocampal neurogenesis and spatial memory in the APPswe\/PS1DeltaE9 mouse model of Alzheimer\u2019s disease. Sci Rep 11(1):22904","journal-title":"Sci Rep"},{"key":"4088_CR15","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/1750-1326-9-61","volume":"9","author":"FG Serrano","year":"2014","unstructured":"Serrano FG, Tapia-Rojas C, Carvajal FJ, Hancke J, Cerpa W, Inestrosa NC (2014) Andrographolide reduces cognitive impairment in young and mature AbetaPPswe\/PS-1 mice. Mol Neurodegener 9:61","journal-title":"Mol Neurodegener"},{"key":"4088_CR16","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.neurobiolaging.2016.06.021","volume":"46","author":"DS Rivera","year":"2016","unstructured":"Rivera DS, Lindsay C, Codocedo JF, Morel I, Pinto C, Cisternas P, Bozinovic F, Inestrosa NC (2016) Andrographolide recovers cognitive impairment in a natural model of Alzheimer\u2019s disease (Octodon degus). Neurobiol Aging 46:204\u2013220","journal-title":"Neurobiol Aging"},{"key":"4088_CR17","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.neuropharm.2018.09.015","volume":"141","author":"X Li","year":"2018","unstructured":"Li X, Wang T, Zhang D, Li H, Shen H, Ding X, Chen G (2018) Andrographolide ameliorates intracerebral hemorrhage induced secondary brain injury by inhibiting neuroinflammation induction. Neuropharmacology 141:305\u2013315","journal-title":"Neuropharmacology"},{"issue":"5","key":"4088_CR18","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1080\/08923973.2017.1344989","volume":"39","author":"R Yang","year":"2017","unstructured":"Yang R, Liu S, Zhou J, Bu S, Zhang J (2017) Andrographolide attenuates microglia-mediated A\u03b2 neurotoxicity partially through inhibiting NF-\u03baB and JNK MAPK signaling pathway. Immunopharmacol Immunotoxicol 39(5):276\u2013284","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"4088_CR19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.pbb.2014.03.028","volume":"122","author":"Z Zhang","year":"2014","unstructured":"Zhang Z, Lai D, Wang L, Yu P, Zhu L, Guo B, Xu L, Zhou L et al (2014) Neuroprotective effects of the andrographolide analogue AL-1 in the MPP+\/MPTP-induced Parkinson\u2019s disease model in vitro and in mice. Pharmacol Biochem Behav 122:191\u2013202","journal-title":"Pharmacol Biochem Behav"},{"issue":"3","key":"4088_CR20","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3109\/13880209.2013.836544","volume":"52","author":"R Bera","year":"2014","unstructured":"Bera R, Ahmed S, Sarkar L, Sen T, Karmakar S (2014) Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS\/MS method. Pharm Biol 52(3):321\u2013329","journal-title":"Pharm Biol"},{"issue":"23","key":"4088_CR21","doi-asserted-by":"publisher","first-page":"4574","DOI":"10.1111\/bph.14823","volume":"176","author":"J Geng","year":"2019","unstructured":"Geng J, Liu W, Gao J, Jiang C, Fan T, Sun Y, Qin ZH, Xu Q et al (2019) Andrographolide alleviates Parkinsonism in MPTP-PD mice via targeting mitochondrial fission mediated by dynamin-related protein 1. Br J Pharmacol 176(23):4574\u20134591","journal-title":"Br J Pharmacol"},{"key":"4088_CR22","doi-asserted-by":"publisher","first-page":"109078","DOI":"10.1016\/j.biopha.2019.109078","volume":"117","author":"J Lu","year":"2019","unstructured":"Lu J, Ma Y, Wu J, Huang H, Wang X, Chen Z, Chen J, He H et al (2019) A review for the neuroprotective effects of andrographolide in the central nervous system. Biomed Pharmacother = Biomedecine Pharmacotherapie 117:109078","journal-title":"Biomed Pharmacother = Biomedecine Pharmacotherapie"},{"key":"4088_CR23","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.bbi.2020.09.017","volume":"91","author":"S Ahmed","year":"2021","unstructured":"Ahmed S, Kwatra M, Ranjan Panda S, Murty USN, Naidu VGM (2021) Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease. Brain Behav Immun 91:142\u2013158","journal-title":"Brain Behav Immun"},{"issue":"12","key":"4088_CR24","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/s41419-019-2195-8","volume":"10","author":"J Gao","year":"2019","unstructured":"Gao J, Peng S, Shan X, Deng G, Shen L, Sun J, Jiang C, Yang X et al (2019) Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis. Cell Death Dis 10(12):957","journal-title":"Cell Death Dis"},{"key":"4088_CR25","doi-asserted-by":"crossref","unstructured":"Gu L, Yu Q, Li Q, Zhang L, Lu H, Zhang X (2018) Andrographolide protects PC12 cells against \u03b2-amyloid-induced autophagy-associated cell death through activation of the Nrf2-mediated p62 signaling pathway. Int J Mol Sci 19(9):undefined","DOI":"10.3390\/ijms19092844"},{"issue":"2","key":"4088_CR26","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1042\/BJ20140207","volume":"466","author":"C Tapia-Rojas","year":"2015","unstructured":"Tapia-Rojas C, Schuller A, Lindsay CB, Ureta RC, Mejias-Reyes C, Hancke J, Melo F, Inestrosa NC (2015) Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3beta: autoregulation of GSK-3beta in vivo. Biochem J 466(2):415\u2013430","journal-title":"Biochem J"},{"key":"4088_CR27","doi-asserted-by":"crossref","unstructured":"Burgos RA, Alarc\u00f3n P, Quiroga J, Manosalva C, Hancke J (2020) Andrographolide, an anti-inflammatory multitarget drug: all roads lead to cellular metabolism. Molecules 26(1):undefined","DOI":"10.3390\/molecules26010005"},{"key":"4088_CR28","doi-asserted-by":"publisher","first-page":"107808","DOI":"10.1016\/j.intimp.2021.107808","volume":"96","author":"J Zhang","year":"2021","unstructured":"Zhang J, Zheng Y, Zhao Y, Zhang Y, Liu Y, Ma F, Wang X, Fu J (2021) Andrographolide ameliorates neuroinflammation in APP\/PS1 transgenic mice. Int Immunopharmacol 96:107808","journal-title":"Int Immunopharmacol"},{"key":"4088_CR29","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.taap.2018.04.037","volume":"350","author":"ZY Zhou","year":"2018","unstructured":"Zhou ZY, Huang B, Li S, Huang XH, Tang JY, Kwan YW, Hoi PM, Lee SM (2018) Sodium tanshinone IIA sulfonate promotes endothelial integrity via regulating VE-cadherin dynamics and RhoA\/ROCK-mediated cellular contractility and prevents atorvastatin-induced intracerebral hemorrhage in zebrafish. Toxicol Appl Pharmacol 350:32\u201342","journal-title":"Toxicol Appl Pharmacol"},{"key":"4088_CR30","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.phrs.2017.09.025","volume":"128","author":"B Huang","year":"2018","unstructured":"Huang B, Zhou ZY, Li S, Huang XH, Tang JY, Hoi MPM, Lee SMY (2018) Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and stabilizes endothelial cell-cell adhesion by inhibiting VE-cadherin internalization and actin-myosin contractility. Pharmacol Res 128:389\u2013398","journal-title":"Pharmacol Res"},{"issue":"7806","key":"4088_CR31","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","volume":"581","author":"A Montagne","year":"2020","unstructured":"Montagne A, Nation DA, Sagare AP, Barisano G, Sweeney MD, Chakhoyan A, Pachicano M, Joe E et al (2020) APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nature 581(7806):71\u201376","journal-title":"Nature"},{"key":"4088_CR32","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.freeradbiomed.2021.05.022","volume":"171","author":"C Mountaki","year":"2021","unstructured":"Mountaki C, Dafnis I, Panagopoulou EA, Vasilakopoulou PB, Karvelas M, Chiou A, Karathanos VT, Chroni A (2021) Mechanistic insight into the capacity of natural polar phenolic compounds to abolish Alzheimer\u2019s disease-associated pathogenic effects of apoE4 forms. Free Radic Biol Med 171:284\u2013301","journal-title":"Free Radic Biol Med"},{"issue":"5","key":"4088_CR33","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00401-016-1547-z","volume":"131","author":"LM Tai","year":"2016","unstructured":"Tai LM, Thomas R, Marottoli FM, Koster KP, Kanekiyo T, Morris AW, Bu G (2016) The role of APOE in cerebrovascular dysfunction. Acta Neuropathol 131(5):709\u2013723","journal-title":"Acta Neuropathol"},{"issue":"7","key":"4088_CR34","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1517\/14728222.2013.789862","volume":"17","author":"H Martiskainen","year":"2013","unstructured":"Martiskainen H, Haapasalo A, Kurkinen K, Pihlajam\u00e4ki J, Soininen H, Hiltunen M (2013) Targeting ApoE4\/ApoE receptor LRP1 in Alzheimer\u2019s disease. Expert Opin Ther Targets 17(7):781\u2013794","journal-title":"Expert Opin Ther Targets"},{"issue":"11","key":"4088_CR35","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1051\/medsci\/20122811006","volume":"28","author":"F Gosselet","year":"2012","unstructured":"Gosselet F (2012) How ApoE regulates blood-brain barrier integrity. Med Sci (Paris) 28(11):920\u2013923","journal-title":"Med Sci (Paris)"},{"issue":"7","key":"4088_CR36","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.neurobiolaging.2006.05.016","volume":"28","author":"BD Zipser","year":"2007","unstructured":"Zipser BD, Johanson CE, Gonzalez L, Berzin TM, Tavares R, Hulette CM, Vitek MP, Hovanesian V et al (2007) Microvascular injury and blood-brain barrier leakage in Alzheimer\u2019s disease. Neurobiol Aging 28(7):977\u2013986","journal-title":"Neurobiol Aging"},{"issue":"11","key":"4088_CR37","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1055\/a-1397-1858","volume":"121","author":"MC Gissler","year":"2021","unstructured":"Gissler MC, Scherrer P, Anto-Michel N, Pennig J, Hoppe N, Funer L, Hardtner C, Stachon P et al (2021) Deficiency of endothelial CD40 induces a stable plaque phenotype and limits inflammatory cell recruitment to atherosclerotic lesions in mice. Thromb Haemost 121(11):1530\u20131540","journal-title":"Thromb Haemost"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-024-04088-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-024-04088-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-024-04088-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T05:26:54Z","timestamp":1726810014000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-024-04088-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,6]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["4088"],"URL":"https:\/\/doi.org\/10.1007\/s12035-024-04088-6","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,6]]},"assertion":[{"value":"23 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"All authors approved the final manuscript and the submission to this journal.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}