{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:28:42Z","timestamp":1783812522447,"version":"3.55.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Biol Toxicol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.<\/jats:p>","DOI":"10.1007\/s10565-024-09878-1","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T02:01:44Z","timestamp":1716256904000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatial transcriptomics reveals gene interactions and signaling pathway dynamics in rat embryos with anorectal malformation"],"prefix":"10.1007","volume":"40","author":[{"given":"Chen-Yi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Gao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Wei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Zuo","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"9878_CR1","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1038\/s41467-018-04724-5","volume":"9","author":"E Berglund","year":"2018","unstructured":"Berglund E, Maaskola J, Schultz N, Friedrich S, Marklund M, Bergenstr\u00e5hle J, Tarish F, Tanoglidi A, Vickovic S, Larsson L, Salm\u00e9n F, Ogris C, Wallenborg K, Lagergren J, St\u00e5hl P, Sonnhammer E, Helleday T, Lundeberg J. Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity. Nat Commun. 2018;9:2419. https:\/\/doi.org\/10.1038\/s41467-018-04724-5.","journal-title":"Nat Commun"},{"key":"9878_CR2","doi-asserted-by":"publisher","first-page":"103625","DOI":"10.1016\/j.compbiomed.2020.103625","volume":"118","author":"P Chalise","year":"2020","unstructured":"Chalise P, Ni Y, Fridley BL. Network-based integrative clustering of multiple types of genomic data using non-negative matrix factorization. Comput Biol Med. 2020;118:103625. https:\/\/doi.org\/10.1016\/j.compbiomed.2020.103625.","journal-title":"Comput Biol Med"},{"key":"9878_CR3","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.jpedsurg.2006.09.012","volume":"42","author":"RA Falcone Jr","year":"2007","unstructured":"Falcone RA Jr, Levitt MA, Pe\u00f1a A, Bates M. Increased heritability of certain types of anorectal malformations. J Pediatr Surg. 2007;42:124\u20137. https:\/\/doi.org\/10.1016\/j.jpedsurg.2006.09.012.","journal-title":"J Pediatr Surg"},{"key":"9878_CR4","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.1002\/ajmg.a.38354","volume":"173","author":"SA Farrell","year":"2017","unstructured":"Farrell SA, Sodhi S, Marshall CR, Guerin A, Slavotinek A, Paton T, Chong K, Sirkin WL, Scherer SW, B\u00e9rub\u00e9-Simard FA, Pilon N. HLX is a candidate gene for a pattern of anomalies associated with congenital diaphragmatic hernia, short bowel, and asplenia. Am J Med Genet A. 2017;173:3070\u20134. https:\/\/doi.org\/10.1002\/ajmg.a.38354.","journal-title":"Am J Med Genet A"},{"issue":"1","key":"9878_CR5","doi-asserted-by":"publisher","first-page":"15799","DOI":"10.1038\/s41598-022-20232-5","volume":"12","author":"YD Heryanto","year":"2022","unstructured":"Heryanto YD, Katayama K, Imoto S. Analyzing integrated network of methylation and gene expression profiles in lung squamous cell carcinoma. Sci Rep. 2022;12(1):15799. https:\/\/doi.org\/10.1038\/s41598-022-20232-5.","journal-title":"Sci Rep"},{"key":"9878_CR6","doi-asserted-by":"publisher","first-page":"194431","DOI":"10.1016\/j.bbagrm.2019.194431","volume":"1863","author":"CH Holland","year":"2020","unstructured":"Holland CH, Szalai B, Saez-Rodriguez J. Transfer of regulatory knowledge from human to mouse for functional genomics analysis. Biochim Biophys Acta Gene Regul Mech. 2020;1863:194431. https:\/\/doi.org\/10.1016\/j.bbagrm.2019.194431.","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"key":"9878_CR7","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s00595-012-0435-y","volume":"43","author":"N Iwai","year":"2013","unstructured":"Iwai N, Fumino S. Surgical treatment of anorectal malformations. Surg Today. 2013;43:955\u201362. https:\/\/doi.org\/10.1007\/s00595-012-0435-y.","journal-title":"Surg Today"},{"key":"9878_CR8","doi-asserted-by":"publisher","first-page":"37137","DOI":"10.1038\/srep37137","volume":"6","author":"A Jemt","year":"2016","unstructured":"Jemt A, Salm\u00e9n F, Lundmark A, Mollbrink A, Fern\u00e1ndez Navarro J, St\u00e5hl PL, Yucel-Lindberg T, Lundeberg J. An automated approach to prepare tissue-derived spatially barcoded RNA-sequencing libraries. Sci Rep. 2016;6:37137. https:\/\/doi.org\/10.1038\/srep37137.","journal-title":"Sci Rep"},{"key":"9878_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.pedneo.2020.09.008","volume":"62","author":"M Kapapa","year":"2021","unstructured":"Kapapa M, Becker N, Serra A. Risk factors for anorectal and associated malformations in German children: A 10-year analysis. Pediatr Neonatol. 2021;62:97\u2013105. https:\/\/doi.org\/10.1016\/j.pedneo.2020.09.008.","journal-title":"Pediatr Neonatol"},{"key":"9878_CR10","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/bdr2.1493","volume":"111","author":"F Kause","year":"2019","unstructured":"Kause F, Zhang R, Ludwig M, Schmiedeke E, Rissmann A, Thiele H, Altmueller J, Herms S, Hilger AC, Hildebrandt F, Reutter H. HSPA6: A new autosomal recessive candidate gene for the VATER\/VACTERL malformation spectrum. Birth Defects Res. 2019;111:591\u20137. https:\/\/doi.org\/10.1002\/bdr2.1493.","journal-title":"Birth Defects Res"},{"key":"9878_CR11","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559. https:\/\/doi.org\/10.1186\/1471-2105-9-559.","journal-title":"BMC Bioinformatics"},{"key":"9878_CR12","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1007\/s00384-011-1191-y","volume":"26","author":"FF Li","year":"2011","unstructured":"Li FF, Zhang T, Bai YZ, Yuan ZW, Wang WL. Spatiotemporal expression of Wnt5a during the development of the hindgut and anorectum in human embryos. Int J Color Dis. 2011;26:983\u20138. https:\/\/doi.org\/10.1007\/s00384-011-1191-y.","journal-title":"Int J Color Dis"},{"key":"9878_CR13","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1007\/s10565-022-09750-0","volume":"39","author":"SY Li","year":"2023","unstructured":"Li SY, Wang CY, Wei XG, Tang XB, Yuan ZW, Bai YZ. CircJag1 promotes apoptosis of ethylene thiourea-exposed anorectal malformations through sponging miR-137-3p by regulating Sox9 and suppressing Wnt\/\u03b2-catenin pathway during the hindgut development of rat embryos. Cell Biol Toxicol. 2023;39:1593\u2013610. https:\/\/doi.org\/10.1007\/s10565-022-09750-0.","journal-title":"Cell Biol Toxicol"},{"key":"9878_CR14","doi-asserted-by":"publisher","first-page":"605015","DOI":"10.3389\/fgene.2021.605015","volume":"12","author":"SY Li","year":"2021","unstructured":"Li SY, Wang CY, Xiao YX, Tang XB, Yuan ZW, Bai YZ. RNA-Seq Profiling of Circular RNAs During Development of Hindgut in Rat Embryos With Ethylenethiourea-Induced Anorectal Malformations. Front Genet. 2021;12:605015. https:\/\/doi.org\/10.3389\/fgene.2021.605015.","journal-title":"Front Genet"},{"key":"9878_CR15","doi-asserted-by":"publisher","first-page":"8060477","DOI":"10.1155\/2021\/8060477","volume":"2021","author":"W Lin","year":"2021","unstructured":"Lin W, Wang Y, Chen Y, Wang Q, Gu Z, Zhu Y. Role of Calcium Signaling Pathway-Related Gene Regulatory Networks in Ischemic Stroke Based on Multiple WGCNA and Single-Cell Analysis. Oxidative Med Cell Longev. 2021;2021:8060477. https:\/\/doi.org\/10.1155\/2021\/8060477.","journal-title":"Oxidative Med Cell Longev"},{"key":"9878_CR16","doi-asserted-by":"publisher","first-page":"4272","DOI":"10.3748\/wjg.v26.i29.4272","volume":"26","author":"D Liu","year":"2020","unstructured":"Liu D, Qu Y, Cao ZN, Jia HM. Rno_circ_0005139 regulates apoptosis by targeting Wnt5a in rat anorectal malformations. World J Gastroenterol. 2020;26:4272\u201387. https:\/\/doi.org\/10.3748\/wjg.v26.i29.4272.","journal-title":"World J Gastroenterol"},{"key":"9878_CR17","doi-asserted-by":"publisher","first-page":"110117","DOI":"10.1016\/j.biopha.2020.110117","volume":"127","author":"CY Long","year":"2020","unstructured":"Long CY, Xiao YX, Li SY, Tang XB, Yuan ZW, Bai YZ. Upregulation of miR-92a-2-5p potentially contribute to anorectal malformations by inhibiting proliferation and enhancing apoptosis via PRKCA\/\u03b2-catenin. Biomed Pharmacother. 2020;127:110117. https:\/\/doi.org\/10.1016\/j.biopha.2020.110117.","journal-title":"Biomed Pharmacother"},{"issue":"2","key":"9878_CR18","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1590\/S0102-86502007000200010","volume":"22","author":"M Macedo","year":"2007","unstructured":"Macedo M, Martins JL, Meyer KF. Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea. Acta Cir Bras. 2007;22(2):130\u20136.","journal-title":"Acta Cir Bras"},{"key":"9878_CR19","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1055\/s-0039-1694743","volume":"29","author":"JL Martins","year":"2019","unstructured":"Martins JL, Macedo M, Montero EFS. Anorectal Malformation: State of the Art in Translating Experimental Research to the Bedside. Eur J Pediatr Surg. 2019;29:368\u201370. https:\/\/doi.org\/10.1055\/s-0039-1694743.","journal-title":"Eur J Pediatr Surg"},{"key":"9878_CR20","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/cdd.2014.21","volume":"21","author":"S Miyagawa","year":"2014","unstructured":"Miyagawa S, Harada M, Matsumaru D, Tanaka K, Inoue C, Nakahara C, Haraguchi R, Matsushita S, Suzuki K, Nakagata N, Ng RC, Akita K, Lui VC, Yamada G. Disruption of the temporally regulated cloaca endodermal \u03b2-catenin signaling causes anorectal malformations. Cell Death Differ. 2014;21:990\u20137. https:\/\/doi.org\/10.1038\/cdd.2014.21.","journal-title":"Cell Death Differ"},{"key":"9878_CR21","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s00383-013-3306-8","volume":"29","author":"SW Moore","year":"2013","unstructured":"Moore SW. Associations of anorectal malformations and related syndromes. Pediatr Surg Int. 2013;29:665\u201376. https:\/\/doi.org\/10.1007\/s00383-013-3306-8.","journal-title":"Pediatr Surg Int"},{"key":"9878_CR22","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/cdd.2014.20","volume":"21","author":"RC Ng","year":"2014","unstructured":"Ng RC, Matsumaru D, Ho AS, Garcia-Barcel\u00f3 MM, Yuan ZW, Smith D, Kodjabachian L, Tam PK, Yamada G, Lui VC. Dysregulation of Wnt inhibitory factor 1 (Wif1) expression resulted in aberrant Wnt-\u03b2-catenin signaling and cell death of the cloaca endoderm, and anorectal malformations. Cell Death Differ. 2014;21:978\u201389. https:\/\/doi.org\/10.1038\/cdd.2014.20.","journal-title":"Cell Death Differ"},{"key":"9878_CR23","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/cancers12010037","volume":"12","author":"M Niemira","year":"2019","unstructured":"Niemira M, Collin F, Szalkowska A, Bielska A, Chwialkowska K, Reszec J, Niklinski J, Kwasniewski M, Kretowski A. Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA). Cancers (Basel). 2019;12:37. https:\/\/doi.org\/10.3390\/cancers12010037.","journal-title":"Cancers (Basel)"},{"key":"9878_CR24","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/978-1-0716-3461-5_13","volume":"2719","author":"C Nithya","year":"2024","unstructured":"Nithya C, Kiran M, Nagarajaram HA. Hubs and Bottlenecks in Protein-Protein Interaction Networks. Methods Mol Biol. 2024;2719:227\u201348. https:\/\/doi.org\/10.1007\/978-1-0716-3461-5_13.","journal-title":"Methods Mol Biol"},{"key":"9878_CR25","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1053\/jpsu.2000.19265","volume":"35","author":"BQ Qi","year":"2000","unstructured":"Qi BQ, Williams A, Beasley S, Frizelle F. Clarification of the process of separation of the cloaca into rectum and urogenital sinus in the rat embryo. J Pediatr Surg. 2000;35:1810\u20136. https:\/\/doi.org\/10.1053\/jpsu.2000.19265.","journal-title":"J Pediatr Surg"},{"key":"9878_CR26","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41467-017-02391-6","volume":"9","author":"M Schubert","year":"2018","unstructured":"Schubert M, Klinger B, Kl\u00fcnemann M, Sieber A, Uhlitz F, Sauer S, Garnett MJ, Bl\u00fcthgen N, Saez-Rodriguez J. Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat Commun. 2018;9:20. https:\/\/doi.org\/10.1038\/s41467-017-02391-6.","journal-title":"Nat Commun"},{"key":"9878_CR27","doi-asserted-by":"publisher","first-page":"4774","DOI":"10.1039\/d2lc00633b","volume":"22","author":"X Shen","year":"2022","unstructured":"Shen X, Zhao Y, Wang Z, Shi Q. Recent advances in high-throughput single-cell transcriptomics and spatial transcriptomics. Lab Chip. 2022;22:4774\u201391. https:\/\/doi.org\/10.1039\/d2lc00633b.","journal-title":"Lab Chip"},{"key":"9878_CR28","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1126\/science.aaf2403","volume":"353","author":"PL St\u00e5hl","year":"2016","unstructured":"St\u00e5hl PL, Salm\u00e9n F, Vickovic S, Lundmark A, Navarro JF, Magnusson J, Giacomello S, Asp M, Westholm JO, Huss M, Mollbrink A, Linnarsson S, Codeluppi S, Borg \u00c5, Pont\u00e9n F, Costea PI, Sahl\u00e9n P, Mulder J, Bergmann O, et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016;353:78\u201382. https:\/\/doi.org\/10.1126\/science.aaf2403.","journal-title":"Science."},{"key":"9878_CR29","doi-asserted-by":"publisher","first-page":"e4445","DOI":"10.7717\/peerj.4445","volume":"6","author":"XB Tang","year":"2018","unstructured":"Tang XB, Li H, Zhang J, Wang WL, Yuan ZW, Bai YZ. Expression pattern of Wif1 and \u03b2-catenin during development of anorectum in fetal rats with anorectal malformations. PeerJ. 2018;6:e4445. https:\/\/doi.org\/10.7717\/peerj.4445.","journal-title":"PeerJ."},{"key":"9878_CR30","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s00383-015-3740-x","volume":"31","author":"AP Theron","year":"2015","unstructured":"Theron AP, Brisighelli G, Theron AE, Leva E, Numanoglu A. Comparison in the incidence of anorectal malformations between a first- and third-world referral center. Pediatr Surg Int. 2015;31:759\u201364. https:\/\/doi.org\/10.1007\/s00383-015-3740-x.","journal-title":"Pediatr Surg Int"},{"key":"9878_CR31","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s00383-015-3685-0","volume":"31","author":"C Wang","year":"2015","unstructured":"Wang C, Li L, Cheng W. Anorectal malformation: the etiological factors. Pediatr Surg Int. 2015;31:795\u2013804. https:\/\/doi.org\/10.1007\/s00383-015-3685-0.","journal-title":"Pediatr Surg Int"},{"key":"9878_CR32","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/nyas.14924","volume":"1518","author":"CY Wang","year":"2022","unstructured":"Wang CY, Li SY, Xiao YX, Zhen L, Wei XG, Tang XB, Yuan ZW, Bai YZ. miR-141-3p affects \u03b2-catenin signaling and apoptosis by targeting Ubtd2 in rats with anorectal malformations. Ann N Y Acad Sci. 2022;1518:315\u201327. https:\/\/doi.org\/10.1111\/nyas.14924.","journal-title":"Ann N Y Acad Sci"},{"key":"9878_CR33","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1093\/bioinformatics\/bty030","volume":"34","author":"K Wong","year":"2018","unstructured":"Wong K, Navarro JF, Bergenstr\u00e5hle L, St\u00e5hl PL, Lundeberg J. ST Spot Detector: a web-based application for automatic spot and tissue detection for spatial Transcriptomics image datasets. Bioinformatics. 2018;34:1966\u20138. https:\/\/doi.org\/10.1093\/bioinformatics\/bty030.","journal-title":"Bioinformatics."},{"key":"9878_CR34","doi-asserted-by":"publisher","first-page":"e70457","DOI":"10.1371\/journal.pone.0070457","volume":"8","author":"LN Wu","year":"2013","unstructured":"Wu LN, Wei XW, Fan Y, Miao JN, Wang LL, Zhang Y, Wu D, Yuan ZW. Altered expression of 14-3-3\u03b6 protein in spinal cords of rat fetuses with spina bifida aperta. PLoS One. 2013;8:e70457. https:\/\/doi.org\/10.1371\/journal.pone.0070457.","journal-title":"PLoS One"},{"key":"9878_CR35","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s00383-018-4311-8","volume":"34","author":"H Xiao","year":"2018","unstructured":"Xiao H, Huang R, Chen L, Diao M, Li L. Integrating lncRNAs and mRNAs expression profiles in terminal hindgut of fetal rats with anorectal malformations. Pediatr Surg Int. 2018;34:971\u201382. https:\/\/doi.org\/10.1007\/s00383-018-4311-8.","journal-title":"Pediatr Surg Int"},{"key":"9878_CR36","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00384-010-1034-2","volume":"26","author":"T Zhang","year":"2011","unstructured":"Zhang T, Zhang HL, Wangda J, Tang XB, Jia HM, Bai YZ, Yuan ZW, Wang WL. Normal development of hindgut and anorectum in human embryo. Int J Color Dis. 2011;26:109\u201316. https:\/\/doi.org\/10.1007\/s00384-010-1034-2.","journal-title":"Int J Color Dis"},{"key":"9878_CR37","doi-asserted-by":"publisher","first-page":"577623","DOI":"10.3389\/fgene.2021.577623","volume":"12","author":"A Zito","year":"2021","unstructured":"Zito A, Lualdi M, Granata P, Cocciadiferro D, Novelli A, Alberio T, Casalone R, Fasano M. Gene Set Enrichment Analysis of Interaction Networks Weighted by Node Centrality. Front Genet. 2021;12:577623. https:\/\/doi.org\/10.3389\/fgene.2021.577623.","journal-title":"Front Genet"}],"container-title":["Cell Biology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10565-024-09878-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10565-024-09878-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10565-024-09878-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T01:28:42Z","timestamp":1735867722000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10565-024-09878-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["9878"],"URL":"https:\/\/doi.org\/10.1007\/s10565-024-09878-1","relation":{},"ISSN":["1573-6822"],"issn-type":[{"value":"1573-6822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"2 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 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":"The animal experiments were conducted in compliance with ethical standards and were approved by the Ethics Committee of Shengjing Hospital, China Medical University (Approval No. 2020PS357K). Consent to participate is not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"34"}}