{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:58:23Z","timestamp":1788991103609,"version":"build-2803163510"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82060285"],"award-info":[{"award-number":["82060285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-76563-y","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T14:03:06Z","timestamp":1729260186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Trophoblast cell-derived extracellular vesicles regulate the polarization of decidual macrophages by carrying miR-141-3p in the pathogenesis of preeclampsia"],"prefix":"10.1038","volume":"14","author":[{"given":"Dongcai","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humin","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"issue":"10297","key":"76563_CR1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S0140-6736(20)32335-7","volume":"398","author":"LC Chappell","year":"2021","unstructured":"Chappell, L. C., Cluver, C. A., Kingdom, J. & Tong, S. Pre-eclampsia. Lancet. 398 (10297), 341\u2013354 (2021).","journal-title":"Lancet"},{"key":"76563_CR2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/cells11152428","volume":"11","author":"M Ogoyama","year":"2022","unstructured":"Ogoyama, M. et al. Non-coding RNAs and prediction of Preeclampsia in the first trimester of pregnancy. Cells. 11, 15 (2022).","journal-title":"Cells"},{"issue":"1\u20132","key":"76563_CR3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1080\/19336918.2015.1106669","volume":"10","author":"PK Lala","year":"2016","unstructured":"Lala, P. K. & Nandi, P. Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: the role of decorin. Cell. Adh Migr. 10(1\u20132), 111\u2013125 (2016).","journal-title":"Cell. Adh Migr."},{"issue":"5","key":"76563_CR4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1095\/biolreprod.113.107805","volume":"88","author":"DB Chen","year":"2013","unstructured":"Chen, D. B. & Wang, W. Human placental microRNAs and preeclampsia. Biol. Reprod. 88(5), 130 (2013).","journal-title":"Biol. Reprod."},{"issue":"3","key":"76563_CR5","doi-asserted-by":"publisher","first-page":"261e261","DOI":"10.1016\/j.ajog.2007.01.008","volume":"196","author":"BL Pineles","year":"2007","unstructured":"Pineles, B. L. et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am. J. Obstet. Gynecol. 196(3), 261e261\u2013261e266 (2007).","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"6","key":"76563_CR6","doi-asserted-by":"publisher","first-page":"661e661","DOI":"10.1016\/j.ajog.2008.12.045","volume":"200","author":"XM Zhu","year":"2009","unstructured":"Zhu, X. M., Han, T., Sargent, I. L., Yin, G. W. & Yao, Y. Q. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am. J. Obstet. Gynecol. 200(6), 661e661\u2013661e667 (2009).","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"5","key":"76563_CR7","doi-asserted-by":"publisher","first-page":"e13857","DOI":"10.1111\/aji.13857","volume":"91","author":"K Nishi","year":"2024","unstructured":"Nishi, K. & Modi, D. Placental exosomes in pregnancy and preeclampsia. Am. J. Reprod. Immunol. 91(5), e13857 (2024).","journal-title":"Am. J. Reprod. Immunol."},{"key":"76563_CR8","doi-asserted-by":"crossref","unstructured":"Yang, L. P., Zheng, J. H., Zhang, J. K. & Huang, X. Dysregulated miR-222-3p in plasma exosomes of preeclampsia patients and its In vitro effect on HTR8\/SVneo extravillous trophoblast cells by targeting STMN1. Human and Experimental Toxicology. ; 2022 (41): 1\u20135. (2022).","DOI":"10.1177\/09603271221138550"},{"issue":"12","key":"76563_CR9","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1007\/s43032-022-00977-0","volume":"29","author":"Z Chen","year":"2022","unstructured":"Chen, Z. et al. Plasma exosomal miR-199a-5p derived from preeclampsia with severe features impairs endothelial cell function via Targeting SIRT1. Reproductive Sci. 29(12), 3413\u20133424 (2022).","journal-title":"Reproductive Sci."},{"key":"76563_CR10","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.placenta.2023.12.003","volume":"145","author":"P Vishnyakova","year":"2024","unstructured":"Vishnyakova, P. et al. MicroRNA miR-27a as a possible regulator of anti-inflammatory macrophage phenotype in preeclamptic placenta. Placenta. 145, 151\u2013161 (2024).","journal-title":"Placenta"},{"issue":"8","key":"76563_CR11","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1089\/dna.2022.0510","volume":"42","author":"H Zhou","year":"2023","unstructured":"Zhou, H. et al. Downregulation of miR-92a in decidual stromal cells suppresses Migration ability of trophoblasts by promoting macrophage polarization. DNA Cell. Biology.  42(8), 507\u2013514 (2023).","journal-title":"DNA Cell. Biology"},{"key":"76563_CR12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.trsl.2016.02.012","volume":"172","author":"S Ospina-Prieto","year":"2016","unstructured":"Ospina-Prieto, S. et al. MicroRNA-141 is upregulated in preeclamptic placentae and regulates trophoblast invasion and intercellular communication. Transl Res. 172, 61\u201372 (2016).","journal-title":"Transl Res."},{"key":"76563_CR13","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.micpath.2018.08.043","volume":"124","author":"X Liu","year":"2018","unstructured":"Liu, X. et al. Decidual macrophage M1 polarization contributes to adverse pregnancy induced by Toxoplasma Gondii PRU strain infection. Microb. Pathog. 124, 183\u2013190 (2018).","journal-title":"Microb. Pathog"},{"key":"76563_CR14","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.placenta.2016.09.004","volume":"47","author":"RJ Buckley","year":"2016","unstructured":"Buckley, R. J., Whitley, G. S., Dumitriu, I. E. & Cartwright, J. E. Macrophage polarisation affects their regulation of trophoblast behaviour. Placenta. 47, 73\u201380 (2016).","journal-title":"Placenta"},{"key":"76563_CR15","doi-asserted-by":"publisher","first-page":"108836","DOI":"10.1016\/j.biopha.2019.108836","volume":"116","author":"D Wu","year":"2019","unstructured":"Wu, D. et al. Hypoxia-induced microRNA-141 regulates trophoblast apoptosis, invasion, and vascularization by blocking CXCL12\u03b2\/CXCR2\/4 signal transduction. Biomed. Pharmacother. 116, 108836 (2019).","journal-title":"Biomed. Pharmacother."},{"issue":"4","key":"76563_CR16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1097\/00004872-199715040-00009","volume":"15","author":"N Kanayama","year":"1997","unstructured":"Kanayama, N., Tsujimura, R., She, L., Maehara, K. & Terao, T. Cold-induced stress stimulates the sympathetic nervous system, causing hypertension and proteinuria in rats. J. Hypertens. 15(4), 383\u2013389 (1997).","journal-title":"J. Hypertens."},{"issue":"4","key":"76563_CR17","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41581-022-00670-0","volume":"19","author":"E Deer","year":"2023","unstructured":"Deer, E. et al. The role of immune cells and mediators in preeclampsia. Nat. Rev. Nephrol. 19(4), 257\u2013270 (2023).","journal-title":"Nat. Rev. Nephrol."},{"issue":"5","key":"76563_CR18","doi-asserted-by":"publisher","first-page":"e12756","DOI":"10.1111\/sji.12756","volume":"90","author":"HQ Lu","year":"2019","unstructured":"Lu, H. Q. & Hu, R. The role of immunity in the pathogenesis and development of pre-eclampsia. Scand. J. Immunol. 90(5), e12756 (2019).","journal-title":"Scand. J. Immunol."},{"key":"76563_CR19","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.placenta.2021.01.011","volume":"104","author":"P Vishnyakova","year":"2021","unstructured":"Vishnyakova, P. et al. Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease. Placenta. 104, 277\u2013283 (2021).","journal-title":"Placenta"},{"key":"76563_CR20","doi-asserted-by":"publisher","first-page":"655655","DOI":"10.3389\/fimmu.2021.655655","volume":"12","author":"M Rong","year":"2021","unstructured":"Rong, M., Yan, X., Zhang, H., Zhou, C. & Zhang, C. Dysfunction of decidual macrophages is a potential risk factor in the occurrence of Preeclampsia. Front. Immunol. 12, 655655 (2021).","journal-title":"Front. Immunol."},{"issue":"1","key":"76563_CR21","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1161\/CIRCRESAHA.116.308304","volume":"119","author":"L Przybyl","year":"2016","unstructured":"Przybyl, L. et al. CD74-Downregulation of placental macrophage-trophoblastic interactions in Preeclampsia. Circ. Res. 119(1), 55\u201368 (2016).","journal-title":"Circ. Res."},{"issue":"3","key":"76563_CR22","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1002\/JLB.1A0420-012RR","volume":"108","author":"YH Zhang","year":"2020","unstructured":"Zhang, Y. H. et al. Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function. J. Leukoc. Biol. 108(3), 983\u2013998 (2020).","journal-title":"J. Leukoc. Biol."},{"issue":"10","key":"76563_CR23","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1161\/HYPERTENSIONAHA.122.19244","volume":"79","author":"X Liu","year":"2022","unstructured":"Liu, X. et al. Trophoblast-derived extracellular vesicles promote Preeclampsia by regulating macrophage polarization. Hypertension 79(10), 2274\u20132287 (2022).","journal-title":"Hypertension"},{"issue":"3","key":"76563_CR24","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1083\/jcb.147.3.599","volume":"147","author":"C Th\u00e9ry","year":"1999","unstructured":"Th\u00e9ry, C. et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J. Cell. Biol. 147(3), 599\u2013610 (1999).","journal-title":"J. Cell. Biol."},{"issue":"10","key":"76563_CR25","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1016\/j.jprot.2010.06.006","volume":"73","author":"S Mathivanan","year":"2010","unstructured":"Mathivanan, S., Ji, H. & Simpson, R. J. Exosomes: extracellular organelles important in intercellular communication. J. Proteom. 73(10), 1907\u20131920 (2010).","journal-title":"J. Proteom."},{"key":"76563_CR26","doi-asserted-by":"crossref","unstructured":"Chen, C. et al. Exosomes: New regulators of reproductive development. Materials Today Bio. ; 19: 100608. (2023).","DOI":"10.1016\/j.mtbio.2023.100608"},{"issue":"4","key":"76563_CR27","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1007\/s43032-022-01059-x","volume":"30","author":"R Pourakbari","year":"2023","unstructured":"Pourakbari, R. et al. Preeclampsia-Derived Exosomes Imbalance the activity of Th17 and Treg in PBMCs from healthy pregnant women. Reproductive Sci. 30(4), 1186\u20131197 (2023).","journal-title":"Reproductive Sci."},{"issue":"6","key":"76563_CR28","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1161\/HYPERTENSIONAHA.118.11706","volume":"72","author":"X Chang","year":"2018","unstructured":"Chang, X. et al. Exosomes from Women with Preeclampsia Induced Vascular Dysfunction by delivering sFlt (Soluble Fms-Like Tyrosine Kinase)-1 and sEng (Soluble Endoglin) to endothelial cells. Hypertension. 72(6), 1381\u20131390 (2018).","journal-title":"Hypertension"},{"issue":"5","key":"76563_CR29","first-page":"741","volume":"52","author":"F Chen","year":"2022","unstructured":"Chen, F., Chen, X., Cai, W., Ruan, H. & Fang, S. Mesenchymal stem cell-derived Exosomal Long Noncoding RNA MALAT1-201 regulated the proliferation, apoptosis and Migration of Trophoblast cells via Targeting miR-141. Ann. Clin. Lab. Sci. 52(5), 741\u2013752 (2022).","journal-title":"Ann. Clin. Lab. Sci."},{"issue":"1","key":"76563_CR30","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1600-0897.2010.00880.x","volume":"65","author":"S Atay","year":"2011","unstructured":"Atay, S., Gercel-Taylor, C., Suttles, J., Mor, G. & Taylor, D. D. Trophoblast-derived exosomes mediate monocyte recruitment and differentiation. Am. J. Reprod. Immunol. 65(1), 65\u201377 (2011).","journal-title":"Am. J. Reprod. Immunol."},{"key":"76563_CR31","doi-asserted-by":"publisher","first-page":"108129","DOI":"10.1016\/j.abb.2019.108129","volume":"676","author":"G Cao","year":"2019","unstructured":"Cao, G., Cui, R., Liu, C. & Zhang, Z. MicroRNA regulation of transthyretin in trophoblast biofunction and preeclampsia. Arch. Biochem. Biophys. 676, 108129 (2019).","journal-title":"Arch. Biochem. Biophys."},{"issue":"10\u201311","key":"76563_CR32","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1159\/000519740","volume":"161","author":"D Wu","year":"2021","unstructured":"Wu, D., Shi, L., Chen, F., Lin, Q. & Kong, J. Methylation status of the mir-141-3p promoter regulates miR-141-3p Expression, inflammasome formation, and the invasiveness of HTR-8\/SVneo cells. Cytogenet. Genome Res. 161(10\u201311), 501\u2013513 (2021).","journal-title":"Cytogenet. Genome Res."},{"issue":"2","key":"76563_CR33","doi-asserted-by":"publisher","first-page":"100483","DOI":"10.1016\/j.repbio.2021.100483","volume":"21","author":"Z Ling","year":"2021","unstructured":"Ling, Z., Chen, M., Li, T., Qian, Y. & Li, C. MiR-141-3p downregulation promotes tube formation, migration, invasion and inhibits apoptosis in hypoxia-induced human umbilical vein endothelial cells by targeting Notch2. Reprod. Biol. 21(2), 100483 (2021).","journal-title":"Reprod. Biol."},{"key":"76563_CR34","doi-asserted-by":"crossref","unstructured":"Zhang, H., Tan, M., Zhang, J., Han, X. & Ma, Y. Propofol Inhibits Thyroid Cancer Cell Proliferation, Migration, and Invasion by Suppressing SHH and PI3K\/AKT Signaling Pathways via the miR-141-3p\/BRD4 Axis. J Healthc Eng. 2021: 2704753. (2021).","DOI":"10.1155\/2021\/2704753"},{"issue":"6","key":"76563_CR35","doi-asserted-by":"publisher","first-page":"e23031","DOI":"10.1002\/jbt.23031","volume":"36","author":"J Ge","year":"2022","unstructured":"Ge, J. et al. SNHG10\/miR-141-3p\/WTAP axis promotes osteosarcoma proliferation and migration. J. Biochem. Mol. Toxicol. 36(6), e23031 (2022).","journal-title":"J. Biochem. Mol. Toxicol."},{"issue":"3","key":"76563_CR36","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.4049\/jimmunol.1402088","volume":"194","author":"H Ying","year":"2015","unstructured":"Ying, H. et al. MiR-127 modulates macrophage polarization and promotes lung inflammation and injury by activating the JNK pathway. J. Immunol. 194(3), 1239\u20131251 (2015).","journal-title":"J. Immunol."},{"issue":"7 Pt A","key":"76563_CR37","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/j.bbamcr.2016.04.003","volume":"1863","author":"K K\u00f6r\u00f6sk\u00e9nyi","year":"2016","unstructured":"K\u00f6r\u00f6sk\u00e9nyi, K., Kiss, B. & Szondy, Z. Adenosine A2A receptor signaling attenuates LPS-induced pro-inflammatory cytokine formation of mouse macrophages by inducing the expression of DUSP1. Biochim. Biophys. Acta 1863(7 Pt A), 1461\u20131471 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"76563_CR38","doi-asserted-by":"publisher","first-page":"108953","DOI":"10.1016\/j.biopha.2019.108953","volume":"115","author":"Y Wang","year":"2019","unstructured":"Wang, Y. et al. Mir-141-5p regulate ATF2 via effecting MAPK1\/ERK2 signaling to promote preeclampsia. Biomed. Pharmacother. 115, 108953 (2019).","journal-title":"Biomed. Pharmacother"},{"issue":"2","key":"76563_CR39","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1080\/10641955.2016.1259627","volume":"36","author":"HA Korkes","year":"2017","unstructured":"Korkes, H. A. et al. Relationship between hypoxia and downstream pathogenic pathways in preeclampsia. Hypertens. Pregnancy. 36(2), 145\u2013150 (2017).","journal-title":"Hypertens. Pregnancy"},{"issue":"1","key":"76563_CR40","doi-asserted-by":"publisher","first-page":"20469","DOI":"10.1038\/s41598-021-99837-1","volume":"11","author":"X Zhou","year":"2021","unstructured":"Zhou, X. et al. Impaired placental mitophagy and oxidative stress are associated with dysregulated BNIP3 in preeclampsia. Sci. Rep. 11(1), 20469 (2021).","journal-title":"Sci. Rep."},{"issue":"3","key":"76563_CR41","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.3892\/mmr.2020.11269","volume":"22","author":"G Chen","year":"2020","unstructured":"Chen, G. et al. Role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice. Mol. Med. Rep. 22(3), 1847\u20131858 (2020).","journal-title":"Mol. Med. Rep."},{"issue":"2","key":"76563_CR42","doi-asserted-by":"publisher","first-page":"3620","DOI":"10.1080\/21655979.2021.1997132","volume":"13","author":"G Chen","year":"2022","unstructured":"Chen, G., Chen, L., Huang, Y., Zhu, X. & Yu, Y. Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells. Bioengineered. 13(2), 3620\u20133633 (2022).","journal-title":"Bioengineered"},{"issue":"9","key":"76563_CR43","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/s41556-018-0176-2","volume":"20","author":"K Palikaras","year":"2018","unstructured":"Palikaras, K., Lionaki, E. & Tavernarakis, N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat. Cell. Biol. 20(9), 1013\u20131022 (2018).","journal-title":"Nat. Cell. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-76563-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-76563-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-76563-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T14:04:53Z","timestamp":1729260293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-76563-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,18]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["76563"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-76563-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,18]]},"assertion":[{"value":"19 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 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":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The animal experiment was approved by the Animal Welfare Committee of Hainan Affiliated Hospital of Hainan Medical University (Med-Eth-Re [2022] 745). We confirm that all methods were reported in accordance with ARRIVE guidelines.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"24529"}}