{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T16:59:06Z","timestamp":1782406746153,"version":"3.54.5"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T00:00:00Z","timestamp":1700870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T00:00:00Z","timestamp":1700870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874255"],"award-info":[{"award-number":["81874255"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2023JDRC0019"],"award-info":[{"award-number":["2023JDRC0019"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2022ZYD0091"],"award-info":[{"award-number":["2022ZYD0091"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2021YJ0194"],"award-info":[{"award-number":["2021YJ0194"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020207","name":"Health Commission of Sichuan Province","doi-asserted-by":"publisher","award":["2023-802"],"award-info":[{"award-number":["2023-802"]}],"id":[{"id":"10.13039\/501100020207","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020207","name":"Health Commission of Sichuan Province","doi-asserted-by":"publisher","award":["21ZD008"],"award-info":[{"award-number":["21ZD008"]}],"id":[{"id":"10.13039\/501100020207","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020207","name":"Health Commission of Sichuan Province","doi-asserted-by":"publisher","award":["2021-803"],"award-info":[{"award-number":["2021-803"]}],"id":[{"id":"10.13039\/501100020207","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Cancer Hospital","award":["YB2023015"],"award-info":[{"award-number":["YB2023015"]}]},{"name":"Sichuan Cancer Hospital","award":["YB2021023"],"award-info":[{"award-number":["YB2021023"]}]},{"name":"Sichuan Cancer Hospital","award":["YBR2019003"],"award-info":[{"award-number":["YBR2019003"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Mammalian intestinal epithelium constantly undergoes rapid self-renewal and regeneration sustained by intestinal stem cells (ISCs) within crypts. Inducible nitric oxide synthase (iNOS) is an important regulator in tissue homeostasis and inflammation. However, the functions of iNOS on ISCs have not been clarified. Here, we aimed to investigate the expression pattern of inducible nitric oxide synthase (iNOS) within crypts and explore its function in the homeostatic maintenance of the ISC niche.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Expression of iNOS was determined by tissue staining and qPCR. iNOS<jats:sup>\u2212\/\u2212<\/jats:sup> and Lgr5 transgenic mice were used to explore the influence of iNOS ablation on ISC proliferation and differentiation. Enteroids were cultured to study the effect of iNOS on ISCs in vitro. Ileum samples from wild-type and iNOS<jats:sup>\u2212\/\u2212<\/jats:sup> mice were collected for RNA-Seq to explore the molecular mechanisms by which iNOS regulates ISCs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>iNOS was physiologically expressed in Paneth cells. Knockout of iNOS led to apparent morphological changes in the intestine, including a decrease in the small intestine length and in the heights of both villi and crypts. Knockout of iNOS decreased the number of Ki67<jats:sup>+<\/jats:sup> or BrdU<jats:sup>+<\/jats:sup> proliferative cells in crypts. Loss of iNOS increased the number of Olfm4<jats:sup>+<\/jats:sup> ISCs but inhibited the differentiation and migration of Lgr5<jats:sup>+<\/jats:sup> ISCs in vivo. iNOS depletion also inhibited enteroid formation and the budding efficiency of crypts in vitro. Moreover, iNOS deficiency altered gluconeogenesis and the adaptive immune response in the ileum transcriptome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Paneth cell-derived iNOS is required to maintain a healthy ISC niche, and Knockout of iNOS hinders ISC function in mice. Therefore, iNOS represents a potential target for the development of new drugs and other therapeutic interventions for intestinal disorders.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-023-04744-w","type":"journal-article","created":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T10:02:18Z","timestamp":1700906538000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Paneth cell-derived iNOS is required to maintain homeostasis in the intestinal stem cell niche"],"prefix":"10.1186","volume":"21","author":[{"given":"Lingxiao","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenni","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudan","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-8067","authenticated-orcid":false,"given":"Dengqun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,25]]},"reference":[{"key":"4744_CR1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1146\/annurev.physiol.010908.163145","volume":"71","author":"LG van der Flier","year":"2009","unstructured":"van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol. 2009;71:241\u201360.","journal-title":"Annu Rev Physiol"},{"key":"4744_CR2","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.cell.2013.07.004","volume":"154","author":"H Clevers","year":"2013","unstructured":"Clevers H. The intestinal crypt, a prototype stem cell compartment. Cell. 2013;154:274\u201384.","journal-title":"Cell"},{"issue":"1262\u201372","key":"4744_CR3","volume":"29","author":"B Palikuqi","year":"2022","unstructured":"Palikuqi B, Rispal J, Reyes EA, Vaka D, Boffelli D, Klein O. Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury. Cell Stem Cell. 2022;29(1262\u201372): e5.","journal-title":"Cell Stem Cell"},{"key":"4744_CR4","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216427","volume":"15","author":"C Wallaeys","year":"2023","unstructured":"Wallaeys C, Garcia-Gonzalez N, Libert C. Paneth cells as the cornerstones of intestinal and organismal health: a primer. EMBO Mol Med. 2023;15: e16427.","journal-title":"EMBO Mol Med"},{"key":"4744_CR5","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature09637","volume":"469","author":"T Sato","year":"2011","unstructured":"Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469:415\u20138.","journal-title":"Nature"},{"key":"4744_CR6","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3389\/fimmu.2020.00587","volume":"11","author":"SR Lueschow","year":"2020","unstructured":"Lueschow SR, McElroy SJ. The Paneth cell: the curator and defender of the immature small intestine. Front Immunol. 2020;11:587.","journal-title":"Front Immunol"},{"key":"4744_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202000180","volume":"43","author":"VN Nikolenko","year":"2021","unstructured":"Nikolenko VN, Oganesyan MV, Sankova MV, Bulygin KV, Vovkogon AD, Rizaeva NA, et al. Paneth cells: maintaining dynamic microbiome-host homeostasis, protecting against inflammation and cancer. BioEssays. 2021;43: e2000180.","journal-title":"BioEssays"},{"issue":"2312\u201328","key":"4744_CR8","volume":"24","author":"M Schmitt","year":"2018","unstructured":"Schmitt M, Schewe M, Sacchetti A, Feijtel D, van de Geer WS, Teeuwssen M, et al. Paneth cells respond to inflammation and contribute to tissue regeneration by acquiring stem-like features through SCF\/c-Kit signaling. Cell Rep. 2018;24(2312\u201328): e7.","journal-title":"Cell Rep"},{"issue":"769\u201378","key":"4744_CR9","volume":"22","author":"MM Mihaylova","year":"2018","unstructured":"Mihaylova MM, Cheng CW, Cao AQ, Tripathi S, Mana MD, Bauer-Rowe KE, et al. Fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging. Cell Stem Cell. 2018;22(769\u201378): e4.","journal-title":"Cell Stem Cell"},{"key":"4744_CR10","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1124\/mol.118.113910","volume":"96","author":"NS Bryan","year":"2019","unstructured":"Bryan NS, Lefer DJ. Update on gaseous signaling molecules nitric oxide and hydrogen sulfide: strategies to capture their functional activity for human therapeutics. Mol Pharmacol. 2019;96:109\u201314.","journal-title":"Mol Pharmacol"},{"key":"4744_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.657457","volume":"12","author":"A Danielak","year":"2021","unstructured":"Danielak A, Wallace JL, Brzozowski T, Magierowski M. Gaseous mediators as a key molecular targets for the development of gastrointestinal-safe anti-inflammatory pharmacology. Front Pharmacol. 2021;12: 657457.","journal-title":"Front Pharmacol"},{"key":"4744_CR12","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.micinf.2015.03.006","volume":"17","author":"J Maloney","year":"2015","unstructured":"Maloney J, Keselman A, Li E, Singer SM. Macrophages expressing arginase 1 and nitric oxide synthase 2 accumulate in the small intestine during Giardia lamblia infection. Microbes Infect. 2015;17:462\u20137.","journal-title":"Microbes Infect"},{"key":"4744_CR13","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1161\/STROKEAHA.122.041444","volume":"54","author":"ZS Katusic","year":"2023","unstructured":"Katusic ZS, d\u2019Uscio LV, He T. Emerging roles of endothelial nitric oxide in preservation of cognitive health. Stroke. 2023;54:686\u201396.","journal-title":"Stroke"},{"key":"4744_CR14","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1096\/fj.06-5798fje","volume":"20","author":"J Bultinck","year":"2006","unstructured":"Bultinck J, Sips P, Vakaet L, Brouckaert P, Cauwels A. Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock. FASEB J. 2006;20:2363\u20135.","journal-title":"FASEB J"},{"key":"4744_CR15","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1042\/CS20180919","volume":"133","author":"S Chai","year":"2019","unstructured":"Chai S, Liu K, Feng W, Liu T, Wang Q, Zhou R, et al. Activation of G protein-coupled estrogen receptor protects intestine from ischemia\/reperfusion injury in mice by protecting the crypt cell proliferation. Clin Sci (Lond). 2019;133:449\u201364.","journal-title":"Clin Sci (Lond)"},{"key":"4744_CR16","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nature06196","volume":"449","author":"N Barker","year":"2007","unstructured":"Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003\u20137.","journal-title":"Nature"},{"key":"4744_CR17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature10408","volume":"478","author":"H Tian","year":"2011","unstructured":"Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011;478:255\u20139.","journal-title":"Nature"},{"key":"4744_CR18","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1073\/pnas.1013004108","volume":"108","author":"RK Montgomery","year":"2011","unstructured":"Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME, Henderson DE, et al. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci USA. 2011;108:179\u201384.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4744_CR19","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cell.2012.02.042","volume":"149","author":"AE Powell","year":"2012","unstructured":"Powell AE, Wang Y, Li Y, Poulin EJ, Means AL, Washington MK, et al. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell. 2012;149:146\u201358.","journal-title":"Cell"},{"key":"4744_CR20","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/ng.165","volume":"40","author":"E Sangiorgi","year":"2008","unstructured":"Sangiorgi E, Capecchi MR. Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 2008;40:915\u201320.","journal-title":"Nat Genet"},{"key":"4744_CR21","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1126\/science.1213214","volume":"334","author":"N Takeda","year":"2011","unstructured":"Takeda N, Jain R, LeBoeuf MR, Wang Q, Lu MM, Epstein JA. Interconversion between intestinal stem cell populations in distinct niches. Science. 2011;334:1420\u20134.","journal-title":"Science"},{"key":"4744_CR22","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1097\/MOG.0000000000000887","volume":"38","author":"VH Lee","year":"2022","unstructured":"Lee VH, Gulati AS. Implications of Paneth cell dysfunction on gastrointestinal health and disease. Curr Opin Gastroenterol. 2022;38:535\u201340.","journal-title":"Curr Opin Gastroenterol"},{"key":"4744_CR23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/BF02955706","volume":"31","author":"J Paneth","year":"1887","unstructured":"Paneth J. Ueber die secernirenden Zellen des D\u00fcnndarm-Epithels. Arch Mikrosk Anat. 1887;31:113\u201391.","journal-title":"Arch Mikrosk Anat"},{"key":"4744_CR24","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1002\/aja.1001260409","volume":"126","author":"H Cheng","year":"1969","unstructured":"Cheng H, Merzel J, Leblond CP. Renewal of Paneth cells in the small intestine of the mouse. Am J Anat. 1969;126:507\u201325.","journal-title":"Am J Anat"},{"key":"4744_CR25","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.3748\/wjg.v24.i17.1881","volume":"24","author":"XY Wang","year":"2018","unstructured":"Wang XY, Chen SH, Zhang YN, Xu CF. Olfactomedin-4 in digestive diseases: a mini-review. World J Gastroenterol. 2018;24:1881\u20137.","journal-title":"World J Gastroenterol"},{"issue":"985\u201399","key":"4744_CR26","volume":"158","author":"L Chen","year":"2020","unstructured":"Chen L, Vasoya RP, Toke NH, Parthasarathy A, Luo S, Chiles E, et al. HNF4 regulates fatty acid oxidation and is required for renewal of intestinal stem cells in mice. Gastroenterology. 2020;158(985\u201399): e9.","journal-title":"Gastroenterology"},{"key":"4744_CR27","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","volume":"459","author":"T Sato","year":"2009","unstructured":"Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459:262\u20135.","journal-title":"Nature"},{"key":"4744_CR28","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/nature16460","volume":"528","author":"CA Lindemans","year":"2015","unstructured":"Lindemans CA, Calafiore M, Mertelsmann AM, O\u2019Connor MH, Dudakov JA, Jenq RR, et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature. 2015;528:560\u20134.","journal-title":"Nature"},{"key":"4744_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118231","volume":"267","author":"C Guo","year":"2021","unstructured":"Guo C, Guo D, Fang L, Sang T, Wu J, Guo C, et al. Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon. Carbohydr Polym. 2021;267: 118231.","journal-title":"Carbohydr Polym"},{"key":"4744_CR30","doi-asserted-by":"publisher","first-page":"6634","DOI":"10.3748\/wjg.v25.i45.6634","volume":"25","author":"YW Xu","year":"2019","unstructured":"Xu YW, Xing RX, Zhang WH, Li L, Wu Y, Hu J, et al. Toxoplasma ROP16(I\/III) ameliorated inflammatory bowel diseases via inducing M2 phenotype of macrophages. World J Gastroenterol. 2019;25:6634\u201352.","journal-title":"World J Gastroenterol"},{"key":"4744_CR31","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/0065-2571(63)90034-7","volume":"1","author":"HA Krebs","year":"1963","unstructured":"Krebs HA. Renal gluconeogenesis. Adv Enzyme Regul. 1963;1:385\u2013400.","journal-title":"Adv Enzyme Regul"},{"key":"4744_CR32","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41575-022-00707-6","volume":"20","author":"A Gautier-Stein","year":"2023","unstructured":"Gautier-Stein A, Mithieux G. Intestinal gluconeogenesis: metabolic benefits make sense in the light of evolution. Nat Rev Gastroenterol Hepatol. 2023;20:183\u201394.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4744_CR33","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/nature21673","volume":"543","author":"MJ Rodriguez-Colman","year":"2017","unstructured":"Rodriguez-Colman MJ, Schewe M, Meerlo M, Stigter E, Gerrits J, Pras-Raves M, et al. Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature. 2017;543:424\u20137.","journal-title":"Nature"},{"issue":"889\u2013900","key":"4744_CR34","volume":"32","author":"MC Ludikhuize","year":"2020","unstructured":"Ludikhuize MC, Meerlo M, Gallego MP, Xanthakis D, Burgaya Julia M, Nguyen NTB, et al. Mitochondria define intestinal stem cell differentiation downstream of a FOXO\/notch axis. Cell Metab. 2020;32(889\u2013900): e7.","journal-title":"Cell Metab"},{"key":"4744_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006179","volume":"12","author":"S Carbajosa","year":"2018","unstructured":"Carbajosa S, Rodriguez-Angulo HO, Gea S, Chillon-Marinas C, Poveda C, Maza MC, et al. L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi. PLoS Negl Trop Dis. 2018;12: e0006179.","journal-title":"PLoS Negl Trop Dis"},{"key":"4744_CR36","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s42003-020-01347-9","volume":"3","author":"Q Hou","year":"2020","unstructured":"Hou Q, Dong Y, Huang J, Liao C, Lei J, Wang Y, et al. Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b. Commun Biol. 2020;3:611.","journal-title":"Commun Biol"},{"key":"4744_CR37","doi-asserted-by":"publisher","first-page":"10299","DOI":"10.1096\/fj.201902573RR","volume":"34","author":"Q Hou","year":"2020","unstructured":"Hou Q, Dong Y, Yu Q, Wang B, Le S, Guo Y, et al. Regulation of the Paneth cell niche by exogenous L-arginine couples the intestinal stem cell function. FASEB J. 2020;34:10299\u2013315.","journal-title":"FASEB J"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04744-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04744-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04744-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T10:07:19Z","timestamp":1700906839000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04744-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,25]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4744"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04744-w","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,25]]},"assertion":[{"value":"22 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experimental procedures were carried out in accordance with the guidelines for the Care and Use of Laboratory Animals and approved by the Ethics Committee of Sichuan Cancer Hospital & Institute (SCCHEC-04-2023-009).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors agree with the content of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"852"}}