{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:16:30Z","timestamp":1772165790104,"version":"3.50.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2016YFE0203900"],"award-info":[{"award-number":["2016YFE0203900"]}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"publisher","award":["SZSM201812055"],"award-info":[{"award-number":["SZSM201812055"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract (GI), which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have suggested\n                      <jats:italic>NADPH oxidase 5<\/jats:italic>\n                      (\n                      <jats:italic>NOX5<\/jats:italic>\n                      ) as a candidate risk gene for HSCR. In this study, we examined the function of\n                      <jats:italic>NOX5<\/jats:italic>\n                      to verify its role in the development of the enteric nervous system (ENS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      HSCR tissue specimens (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) were collected at the time of pull-through surgery and control specimens (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) were obtained at the time of colostomy closure in patients. The\n                      <jats:italic>NOX5<\/jats:italic>\n                      expression in aganglionic and ganglionic segments of HSCR colon and normal colon were analyzed by immunohistochemistry (IHC), western blot and real-time quantitative PCR (qPCR). The gene expression levels and spatiotemporal expression spectrum of\n                      <jats:italic>NOX5<\/jats:italic>\n                      in different development stages of zebrafish embryo were determined using qPCR and in-situ hybridization (ISH). The enteric nervous system in\n                      <jats:italic>NOX5<\/jats:italic>\n                      Morpholino (MO) knockdown and wild type (WT) zebrafish embryo was analyzed by whole-mount immunofluorescence (IF). Intestinal transit assay was performed to analyze the gastrointestinal motility in\n                      <jats:italic>NOX5<\/jats:italic>\n                      knockdown and control larvae.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>NOX5<\/jats:italic>\n                      is strongly expressed in the ganglion cells in the proximal segment of HSCR colons and all segments of normal colons. Moreover, the expression of\n                      <jats:italic>NOX5<\/jats:italic>\n                      is markedly decreased in the aganglionic segment of HSCR colon compared to the ganglionic segment. In zebrafish,\n                      <jats:italic>NOX5<\/jats:italic>\n                      mRNA level is the highest in the one cell stage embryos and it is decreased overtime with the development of the embryos. Interestingly, the expression of\n                      <jats:italic>NOX5<\/jats:italic>\n                      appears to be enriched in the nervous system. However, the number of neurons in the GI tract and the GI motility were not affected upon\n                      <jats:italic>NOX5<\/jats:italic>\n                      knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study shows that\n                      <jats:italic>NOX5<\/jats:italic>\n                      markedly decreased in the aganglionic segment of HSCR but didn\u2019t involve in the ENS development of zebrafish. It implies that absence of intestinal ganglion cells may lead to down-regulation of\n                      <jats:italic>NOX5<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12887-021-02611-5","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T03:02:51Z","timestamp":1617073371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["NOX5 is expressed aberrantly but not a critical pathogenetic gene in Hirschsprung disease"],"prefix":"10.1186","volume":"21","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyao","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xufeng","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di Di","family":"Zhuansun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiexiong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"issue":"11","key":"2611_CR1","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1007\/s00383-016-3961-7","volume":"32","author":"X Chen","year":"2016","unstructured":"Chen X, Zhang H, Li N, Feng J. Pathological changes of interstitial cells of Cajal and ganglion cells in the segment of resected bowel in Hirschsprung's disease. Pediatr Surg Int. 2016;32(11):1019\u201324. https:\/\/doi.org\/10.1007\/s00383-016-3961-7.","journal-title":"Pediatr Surg Int"},{"issue":"3","key":"2611_CR2","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1097\/MOP.0b013e328360c2a0","volume":"25","author":"JC Langer","year":"2013","unstructured":"Langer JC. Hirschsprung disease. Curr Opin Pediatr. 2013;25(3):368\u201374. https:\/\/doi.org\/10.1097\/MOP.0b013e328360c2a0.","journal-title":"Curr Opin Pediatr"},{"issue":"4","key":"2611_CR3","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1089\/lap.2017.0275","volume":"28","author":"C Jiao","year":"2018","unstructured":"Jiao C, Yu D, Li D, Wang G, Feng J. A long-term follow-up of a new surgery method: laparoscope-assisted heart-shaped anastomosis for Hirschsprung's disease. J Laparoendosc Adv Surg Tech Part A. 2018;28(4):471\u20135. https:\/\/doi.org\/10.1089\/lap.2017.0275.","journal-title":"J Laparoendosc Adv Surg Tech Part A"},{"key":"2611_CR4","doi-asserted-by":"crossref","unstructured":"Luzon-Toro B, Villalba-Benito L, Torroglosa A, Fernandez RM, Antinolo G, Borrego S. What is new about the genetic background of Hirschsprung disease? Clin Genetics. 2020;97(1):114\u201324.","DOI":"10.1111\/cge.13615"},{"issue":"1","key":"2611_CR5","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13059-017-1174-6","volume":"18","author":"H Gui","year":"2017","unstructured":"Gui H, Schriemer D, Cheng WW, Chauhan RK, Antinolo G, Berrios C, et al. Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes. Genome Biol. 2017;18(1):48. https:\/\/doi.org\/10.1186\/s13059-017-1174-6.","journal-title":"Genome Biol"},{"issue":"15","key":"2611_CR6","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1056\/NEJMoa1706594","volume":"380","author":"JM Tilghman","year":"2019","unstructured":"Tilghman JM, Ling AY, Turner TN, Sosa MX, Krumm N, Chatterjee S, Kapoor A, Coe BP, Nguyen KDH, Gupta N, Gabriel S, Eichler EE, Berrios C, Chakravarti A. Molecular genetic anatomy and risk profile of Hirschsprung's disease. N Engl J Med. 2019;380(15):1421\u201332. https:\/\/doi.org\/10.1056\/NEJMoa1706594.","journal-title":"N Engl J Med"},{"key":"2611_CR7","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fped.2020.00060","volume":"8","author":"KAS Gunadi","year":"2020","unstructured":"Gunadi KAS, Budi NYP, Hafiq HM, Maharani A, Febrianti M, et al. Aberrant Expressions and Variant Screening of SEMA3D in Indonesian Hirschsprung Patients. Front Pediatr. 2020;8:60.","journal-title":"Front Pediatr"},{"issue":"4","key":"2611_CR8","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.ajhg.2015.02.014","volume":"96","author":"Q Jiang","year":"2015","unstructured":"Jiang Q, Arnold S, Heanue T, Kilambi KP, Doan B, Kapoor A, Ling AY, Sosa MX, Guy M, Jiang Q, Burzynski G, West K, Bessling S, Griseri P, Amiel J, Fernandez RM, Verheij JBGM, Hofstra RMW, Borrego S, Lyonnet S, Ceccherini I, Gray JJ, Pachnis V, McCallion AS, Chakravarti A. Functional loss of semaphorin 3C and\/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. Am J Hum Genet. 2015;96(4):581\u201396. https:\/\/doi.org\/10.1016\/j.ajhg.2015.02.014.","journal-title":"Am J Hum Genet"},{"issue":"11","key":"2611_CR9","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s00383-016-3953-7","volume":"32","author":"Gunadi","year":"2016","unstructured":"Gunadi, Makhmudi A, Agustriani N, Rochadi. Effects of SEMA3 polymorphisms in Hirschsprung disease patients. Pediatr Surg Int. 2016;32(11):1025\u20138. https:\/\/doi.org\/10.1007\/s00383-016-3953-7.","journal-title":"Pediatr Surg Int"},{"issue":"8","key":"2611_CR10","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1073\/pnas.0809630105","volume":"106","author":"MM Garcia-Barcelo","year":"2009","unstructured":"Garcia-Barcelo MM, Tang CS, Ngan ES, Lui VC, Chen Y, So MT, Leon TYY, Miao XP, Shum CKY, Liu FQ, Yeung MY, Yuan ZW, Guo WH, Liu L, Sun XB, Huang LM, Tou JF, Song YQ, Chan D, Cheung KMC, Wong KKY, Cherny SS, Sham PC, Tam PKH. Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease. Proc Natl Acad Sci U S A. 2009;106(8):2694\u20139. https:\/\/doi.org\/10.1073\/pnas.0809630105.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2611_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002687","volume":"8","author":"CS Tang","year":"2012","unstructured":"Tang CS, Cheng G, So MT, Yip BH, Miao XP, Wong EH, et al. Genome-wide copy number analysis uncovers a new HSCR gene: NRG3. PLoS Genet. 2012;8(5):e1002687. https:\/\/doi.org\/10.1371\/journal.pgen.1002687.","journal-title":"PLoS Genet"},{"issue":"10","key":"2611_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110292","volume":"9","author":"JH Kim","year":"2014","unstructured":"Kim JH, Cheong HS, Sul JH, Seo JM, Kim DY, Oh JT, Park KW, Kim HY, Jung SM, Jung K, Cho MJ, Bae JS, Shin HD. A genome-wide association study identifies potential susceptibility loci for Hirschsprung disease. PLoS One. 2014;9(10):e110292. https:\/\/doi.org\/10.1371\/journal.pone.0110292.","journal-title":"PLoS One"},{"issue":"9","key":"2611_CR13","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1016\/j.jpedsurg.2018.12.017","volume":"54","author":"JG Shin","year":"2019","unstructured":"Shin JG, Seo JY, Seo JM, Kim DY, Oh JT, Park KW, Kim HY, Kim JH, Shin HD. Association analysis of NOX5 polymorphisms with Hirschsprung disease. J Pediatr Surg. 2019;54(9):1815\u20139. https:\/\/doi.org\/10.1016\/j.jpedsurg.2018.12.017.","journal-title":"J Pediatr Surg"},{"issue":"1","key":"2611_CR14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1152\/physrev.00044.2005","volume":"87","author":"K Bedard","year":"2007","unstructured":"Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245\u2013313. https:\/\/doi.org\/10.1152\/physrev.00044.2005.","journal-title":"Physiol Rev"},{"issue":"2","key":"2611_CR15","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.tcb.2011.11.002","volume":"22","author":"TR Hurd","year":"2012","unstructured":"Hurd TR, DeGennaro M, Lehmann R. Redox regulation of cell migration and adhesion. Trends Cell Biol. 2012;22(2):107\u201315. https:\/\/doi.org\/10.1016\/j.tcb.2011.11.002.","journal-title":"Trends Cell Biol"},{"issue":"22","key":"2611_CR16","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1016\/j.jacc.2008.08.040","volume":"52","author":"E Schulz","year":"2008","unstructured":"Schulz E, Munzel T. NOX5, a new \"radical\" player in human atherosclerosis? J Am Coll Cardiol. 2008;52(22):1810\u20132. https:\/\/doi.org\/10.1016\/j.jacc.2008.08.040.","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"2611_CR17","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1161\/HYPERTENSIONAHA.109.142422","volume":"56","author":"SR Datla","year":"2010","unstructured":"Datla SR, Griendling KK. Reactive oxygen species, NADPH oxidases, and hypertension. Hypertension (Dallas, Tex : 1979). 2010;56(3):325\u201330.","journal-title":"Hypertension (Dallas, Tex : 1979)"},{"issue":"4","key":"2611_CR18","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.freeradbiomed.2011.11.023","volume":"52","author":"K Bedard","year":"2012","unstructured":"Bedard K, Jaquet V, Krause KH. NOX5: from basic biology to signaling and disease. Free Radic Biol Med. 2012;52(4):725\u201334. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2011.11.023.","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"2611_CR19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00441-013-1775-7","volume":"356","author":"J Wei","year":"2014","unstructured":"Wei J, Li N, Xia X, Chen X, Peng F, Besner GE, Feng J. Effects of lipopolysaccharide-induced inflammation on the interstitial cells of Cajal. Cell Tissue Res. 2014;356(1):29\u201337. https:\/\/doi.org\/10.1007\/s00441-013-1775-7.","journal-title":"Cell Tissue Res"},{"key":"2611_CR20","volume-title":"The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio)","author":"MW","year":"2000","unstructured":"MW. The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio). Eugene, OR: University of Oregon Press; 2000."},{"key":"2611_CR21","doi-asserted-by":"publisher","first-page":"144049","DOI":"10.1016\/j.gene.2019.144049","volume":"718","author":"S Balasubramanian","year":"2019","unstructured":"Balasubramanian S, Raghunath A, Perumal E. Role of epigenetics in zebrafish development. Gene. 2019;718:144049. https:\/\/doi.org\/10.1016\/j.gene.2019.144049.","journal-title":"Gene."},{"issue":"1","key":"2611_CR22","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nprot.2007.514","volume":"3","author":"C Thisse","year":"2008","unstructured":"Thisse C, Thisse B. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc. 2008;3(1):59\u201369. https:\/\/doi.org\/10.1038\/nprot.2007.514.","journal-title":"Nat Protoc"},{"issue":"10","key":"2611_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007000","volume":"13","author":"DYR Stainier","year":"2017","unstructured":"Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, Ingham PW, Schulte-Merker S, Yelon D, Weinstein BM, Mullins MC, Wilson SW, Ramakrishnan L, Amacher SL, Neuhauss SCF, Meng A, Mochizuki N, Panula P, Moens CB. Guidelines for morpholino use in zebrafish. PLoS Genet. 2017;13(10):e1007000. https:\/\/doi.org\/10.1371\/journal.pgen.1007000.","journal-title":"PLoS Genet"},{"issue":"3","key":"2611_CR24","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1111\/j.1365-2982.2008.01234.x","volume":"21","author":"HA Field","year":"2009","unstructured":"Field HA, Kelley KA, Martell L, Goldstein AM, Serluca FC. Analysis of gastrointestinal physiology using a novel intestinal transit assay in zebrafish. Neurogastroenterol Motility. 2009;21(3):304\u201312. https:\/\/doi.org\/10.1111\/j.1365-2982.2008.01234.x.","journal-title":"Neurogastroenterol Motility"},{"issue":"1","key":"2611_CR25","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/jcb.26149","volume":"119","author":"A Bahrami","year":"2018","unstructured":"Bahrami A, Joodi M, Moetamani-Ahmadi M, Maftouh M, Hassanian SM, Ferns GA, Avan A. Genetic background of Hirschsprung disease: a bridge between basic science and clinical application. J Cell Biochem. 2018;119(1):28\u201333. https:\/\/doi.org\/10.1002\/jcb.26149.","journal-title":"J Cell Biochem"},{"issue":"5","key":"2611_CR26","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1113\/EP086204","volume":"104","author":"RM Touyz","year":"2019","unstructured":"Touyz RM, Anagnostopoulou A, Rios F, Montezano AC, Camargo LL. NOX5: molecular biology and pathophysiology. Exp Physiol. 2019;104(5):605\u201316. https:\/\/doi.org\/10.1113\/EP086204.","journal-title":"Exp Physiol"},{"issue":"3","key":"2611_CR27","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1161\/HYPERTENSIONAHA.120.15558","volume":"76","author":"GJ Zhao","year":"2020","unstructured":"Zhao GJ, Zhao CL, Ouyang S, Deng KQ, Zhu L, Montezano AC, Zhang C, Hu F, Zhu XY, Tian S, Liu X, Ji YX, Zhang P, Zhang XJ, She ZG, Touyz RM, Li H. Ca (2+)-dependent NOX5 (NADPH oxidase 5) exaggerates cardiac hypertrophy through reactive oxygen species production. Hypertension. 2020;76(3):827\u201338. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.120.15558.","journal-title":"Hypertension."},{"issue":"4","key":"2611_CR28","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1021\/bi901846y","volume":"49","author":"F Tirone","year":"2010","unstructured":"Tirone F, Radu L, Craescu CT, Cox JA. Identification of the binding site for the regulatory calcium-binding domain in the catalytic domain of NOX5. Biochemistry. 2010;49(4):761\u201371. https:\/\/doi.org\/10.1021\/bi901846y.","journal-title":"Biochemistry."},{"issue":"1","key":"2611_CR29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1752-153X-6-29","volume":"6","author":"CC Wei","year":"2012","unstructured":"Wei CC, Reynolds N, Palka C, Wetherell K, Boyle T, Yang YP, Wang ZQ, Stuehr DJ. Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism. Chem Central J. 2012;6(1):29. https:\/\/doi.org\/10.1186\/1752-153X-6-29.","journal-title":"Chem Central J"},{"issue":"26","key":"2611_CR30","doi-asserted-by":"crossref","first-page":"6764","DOI":"10.1073\/pnas.1702293114","volume":"114","author":"F Magnani","year":"2017","unstructured":"Magnani F, Nenci S, Millana Fananas E, Ceccon M, Romero E, Fraaije MW, et al. Crystal structures and atomic model of NADPH oxidase. Proc Natl Acad Sci U S A. 2017;114(26):6764\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"2611_CR31","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1002\/cne.23938","volume":"524","author":"CJ Weaver","year":"2016","unstructured":"Weaver CJ, Leung YF, Suter DM. Expression dynamics of NADPH oxidases during early zebrafish development. J Comp Neurol. 2016;524(10):2130\u201341. https:\/\/doi.org\/10.1002\/cne.23938.","journal-title":"J Comp Neurol"},{"key":"2611_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/164_2016_118","volume":"239","author":"B Greenwood-Van Meerveld","year":"2017","unstructured":"Greenwood-Van Meerveld B, Johnson AC, Grundy D. Gastrointestinal physiology and function. Handb Exp Pharmacol. 2017;239:1\u201316. https:\/\/doi.org\/10.1007\/164_2016_118.","journal-title":"Handb Exp Pharmacol"},{"issue":"6","key":"2611_CR33","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41575-020-0271-2","volume":"17","author":"NJ Spencer","year":"2020","unstructured":"Spencer NJ, Hu H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol. 2020;17(6):338\u201351. https:\/\/doi.org\/10.1038\/s41575-020-0271-2.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"2611_CR34","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1186\/s12887-019-1879-7","volume":"19","author":"Gunadi","year":"2019","unstructured":"Gunadi, Kalim AS, Liana E, Fauzi AR, Sirait DN, Afandy D, et al. Aberrant UBR4 expressions in Hirschsprung disease patients. BMC Pediatr. 2019;19(1):493.","journal-title":"BMC Pediatr"},{"issue":"8","key":"2611_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202260","volume":"13","author":"ST Kim","year":"2018","unstructured":"Kim ST, Lee YJ, Tasaki T, Hwang J, Kang MJ, Yi EC, Kim BY, Kwon YT. The N-recognin UBR4 of the N-end rule pathway is required for neurogenesis and homeostasis of cell surface proteins. PLoS One. 2018;13(8):e0202260. https:\/\/doi.org\/10.1371\/journal.pone.0202260.","journal-title":"PLoS One"},{"issue":"5","key":"2611_CR36","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.celrep.2019.06.094","volume":"28","author":"LC Hunt","year":"2019","unstructured":"Hunt LC, Stover J, Haugen B, Shaw TI, Li Y, Pagala VR, et al. A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice. Cell Rep. 2019;28(5):1268\u201381 e6.","journal-title":"Cell Rep"},{"issue":"40","key":"2611_CR37","doi-asserted-by":"publisher","first-page":"37594","DOI":"10.1074\/jbc.M103034200","volume":"276","author":"B Banfi","year":"2001","unstructured":"Banfi B, Molnar G, Maturana A, Steger K, Hegedus B, Demaurex N, et al. A Ca (2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem. 2001;276(40):37594\u2013601. https:\/\/doi.org\/10.1074\/jbc.M103034200.","journal-title":"J Biol Chem"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-021-02611-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12887-021-02611-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-021-02611-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T16:23:04Z","timestamp":1671726184000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-021-02611-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2611"],"URL":"https:\/\/doi.org\/10.1186\/s12887-021-02611-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-45296\/v1","asserted-by":"object"}]},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]},"assertion":[{"value":"7 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2021","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 Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology approved the protocol of the study (The ethical approval number: 2019-HP0761). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The informed written consents were obtained from the patients or patients\u2019 guardian.","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 conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"153"}}