{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:37:03Z","timestamp":1787020623340,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH-1097325D, TCVGH-1107301D, TCVGH-1117301D, TCVGH-1113602D, TCVGH-1127301D, TCVGH-1123602D, TCVGH-1137301D, and TCVGH-1133602D"],"award-info":[{"award-number":["TCVGH-1097325D, TCVGH-1107301D, TCVGH-1117301D, TCVGH-1113602D, TCVGH-1127301D, TCVGH-1123602D, TCVGH-1137301D, and TCVGH-1133602D"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science and Technology Council","award":["MOST 111-2314-B-075A-004"],"award-info":[{"award-number":["MOST 111-2314-B-075A-004"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hyperactive neutrophil extracellular traps (NETs) formation plays a crucial role in active severe systemic lupus erythematosus (SLE). However, what triggers the imbalance in dysregulated NETs formation in SLE is elusive. Transfer RNA-derived small RNAs (tsRNAs) are novel non-coding RNAs, which participate in various cellular processes. We explore the role of tsRNAs on NETs formation in SLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed the levels of NETs DNA and platelet-derived extracellular vesicles (pEVs) from 50 SLE patients and 20 healthy control subjects. The effects of pEVs on NETs formation were evaluated by using immunofluorescence assay and myeloperoxidase-DNA PicoGreen assay. The regulatory mechanism of pEVs on NETs formation and inflammatory cytokines production were investigated using an in vitro cell-based assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increased circulating NETs DNA and pEVs were shown in SLE patients and were associated with disease activity (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.005). We demonstrated that SLE patient-derived immune complexes (ICs) induced platelet activation, followed by pEVs release. ICs-triggered NETs formation was significantly enhanced in the presence of pEVs through Toll-like receptor (TLR) 8 activation. Increased levels of tRF-His-GTG-1 in pEVs and neutrophils of SLE patients were associated with disease activity. tRF-His-GTG-1 interacted with TLR8 to prime p47phox phosphorylation in neutrophils, resulting in reactive oxygen species production and NETs formation. Additionally, tRF-His-GTG-1 modulated NF-\u03baB and IRF7 activation in neutrophils upon TLR8 engagement, resulting IL-1\u03b2, IL-8, and interferon-\u03b1 upregulation, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The level of tRF-His-GTG-1 was positively correlated with NETs formation in SLE patients; tRF-His-GTG-1 inhibitor could efficiently suppress ICs-triggered NETs formation\/hyperactivation, which may become a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-024-01730-7","type":"journal-article","created":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T12:01:23Z","timestamp":1720353683000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["tRF-His-GTG-1 enhances NETs formation and interferon-\u03b1 production in lupus by extracellular vesicle"],"prefix":"10.1186","volume":"22","author":[{"given":"Yi-Ming","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Tung","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Jen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ting","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Ling","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,7]]},"reference":[{"key":"1730_CR1","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1056\/NEJMra1100359","volume":"365","author":"GC Tsokos","year":"2011","unstructured":"Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365:2110\u201321.","journal-title":"N Engl J Med"},{"key":"1730_CR2","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/nrrheum.2012.118","volume":"8","author":"E Boilard","year":"2012","unstructured":"Boilard E, Blanco P, Nigrovic PA. Platelets: active players in the pathogenesis of arthritis and SLE. Nat Rev Rheumatol. 2012;8:534\u201342.","journal-title":"Nat Rev Rheumatol"},{"key":"1730_CR3","doi-asserted-by":"publisher","first-page":"eaav5928","DOI":"10.1126\/scitranslmed.aav5928","volume":"13","author":"I Melki","year":"2021","unstructured":"Melki I, Allaeys I, Tessandier N, et al. Platelets release mitochondrial antigens in systemic lupus erythematosus. Sci Transl Med. 2021;13:eaav5928.","journal-title":"Sci Transl Med"},{"key":"1730_CR4","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ijcard.2017.02.107","volume":"236","author":"P Lopez","year":"2017","unstructured":"Lopez P, Rodriguez-Carrio J, Martinez-Zapico A, Caminal-Montero L, Suarez A. Circulating microparticle subpopulations in systemic lupus erythematosus are affected by disease activity. Int J Cardiol. 2017;236:138\u201344.","journal-title":"Int J Cardiol"},{"key":"1730_CR5","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13075-016-1159-y","volume":"18","author":"JY Lee","year":"2016","unstructured":"Lee JY, Park JK, Lee EY, Lee EB, Song YW. Circulating exosomes from patients with systemic lupus erythematosus induce a proinflammatory immune response. Arthritis Res Ther. 2016;18:264.","journal-title":"Arthritis Res Ther"},{"key":"1730_CR6","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1056\/NEJMra1704286","volume":"379","author":"R Shah","year":"2018","unstructured":"Shah R, Patel T, Freedman JE. Circulating Extracellular vesicles in Human Disease. N Engl J Med. 2018;379:958\u201366.","journal-title":"N Engl J Med"},{"key":"1730_CR7","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12943-019-1000-8","volume":"18","author":"L Zhu","year":"2019","unstructured":"Zhu L, Li J, Gong Y, Wu Q, Tan S, Sun D, et al. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis. Mol Cancer. 2019;18:74.","journal-title":"Mol Cancer"},{"key":"1730_CR8","doi-asserted-by":"publisher","first-page":"461","DOI":"10.7150\/thno.51963","volume":"11","author":"X Yu","year":"2021","unstructured":"Yu X, Xie Y, Zhang S, Song X, Xiao B, Yan Z. tRNA-derived fragments: mechanisms underlying their regulation of gene expression and potential applications as therapeutic targets in cancers and virus infections. Theranostics. 2021;11:461\u20139.","journal-title":"Theranostics"},{"key":"1730_CR9","doi-asserted-by":"publisher","first-page":"735105","DOI":"10.3389\/fimmu.2021.735105","volume":"12","author":"P Yang","year":"2021","unstructured":"Yang P, Zhang X, Chen S, Tao Y, Ning M, Zhu Y, et al. A novel serum tsRNA for diagnosis and prediction of Nephritis in SLE. Front Immunol. 2021;12:735105.","journal-title":"Front Immunol"},{"key":"1730_CR10","doi-asserted-by":"publisher","first-page":"1077645","DOI":"10.3389\/fimmu.2023.1077645","volume":"14","author":"S Chen","year":"2023","unstructured":"Chen S, Zhang X, Meng K, Sun Y, Shu R, Han T, et al. Urinary exosome tsRNAs as novel markers for diagnosis and prediction of lupus nephritis. Front Immunol. 2023;14:1077645.","journal-title":"Front Immunol"},{"key":"1730_CR11","doi-asserted-by":"publisher","first-page":"3284","DOI":"10.4049\/jimmunol.0902199","volume":"184","author":"MF Denny","year":"2010","unstructured":"Denny MF, Yalavarthi S, Zhao W, Thacker SG, Anderson M, Sandy AR, et al. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J Immunol. 2010;184:3284\u201397.","journal-title":"J Immunol"},{"key":"1730_CR12","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/nm.4027","volume":"22","author":"C Lood","year":"2016","unstructured":"Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, de Ravin SS, Smith CK, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus- like disease. Nat Med. 2016;22:146\u201353.","journal-title":"Nat Med"},{"key":"1730_CR13","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/art.1780400928","volume":"40","author":"MC Hochberg","year":"1997","unstructured":"Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.","journal-title":"Arthritis Rheum"},{"key":"1730_CR14","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1002\/art.34473","volume":"64","author":"M Petri","year":"2012","unstructured":"Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic Lupus International collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677\u201386.","journal-title":"Arthritis Rheum"},{"key":"1730_CR15","doi-asserted-by":"publisher","first-page":"27031","DOI":"10.3402\/jev.v4.27031","volume":"4","author":"RJ Lobb","year":"2015","unstructured":"Lobb RJ, Becker M, Wen SW, Wong CSF, Wiegmans AP, Leimgruber A, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles. 2015;4:27031.","journal-title":"J Extracell Vesicles"},{"key":"1730_CR16","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1136\/ard.62.1.37","volume":"62","author":"J R\u00f6nnelid","year":"2003","unstructured":"R\u00f6nnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B. Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an Fc\u03b3RII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE. Ann Rheum Dis. 2003;62:37\u201342.","journal-title":"Ann Rheum Dis"},{"key":"1730_CR17","doi-asserted-by":"publisher","first-page":"2001562","DOI":"10.1183\/13993003.01562-2020","volume":"57","author":"J Krug","year":"2021","unstructured":"Krug J, Kiefer A, Koelle J, Vuorinen T, Xepapadaki P, Stanic B, et al. TLR7\/8 regulates type I and type III interferon signalling in rhinovirus 1b-induced allergic asthma. Eur Respir J. 2021;57:2001562.","journal-title":"Eur Respir J"},{"key":"1730_CR18","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","volume":"7","author":"C Th\u00e9ry","year":"2018","unstructured":"Th\u00e9ry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7:1535750.","journal-title":"J Extracell Vesicles"},{"key":"1730_CR19","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.1182\/blood-2003-04-1078","volume":"102","author":"F Hayashi","year":"2003","unstructured":"Hayashi F, Means TK, Luster AD. Toll-like receptors stimulate human neutrophil function. Blood. 2003;102:2660\u20139.","journal-title":"Blood"},{"key":"1730_CR20","doi-asserted-by":"publisher","first-page":"e0276421","DOI":"10.1128\/mBio.02764-21","volume":"12","author":"TL Liao","year":"2021","unstructured":"Liao TL, Chen YM, Hsieh SL, Tang KT, Chen DY, Yang YY, et al. Hepatitis C virus-induced exosomal microRNAs and TLR7 polymorphism regulate B-cell activating factor. mBio. 2021;12:e0276421.","journal-title":"mBio"},{"key":"1730_CR21","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1189\/jlb.2A1214-623R","volume":"97","author":"MM Karama","year":"2015","unstructured":"Karama MM, Viviana M, Tarek B, Sahra AB, Marie-Anne GP, Margarita HN, et al. TLR8, but not TLR7, induces the priming of the NADPH oxidase activation in human neutrophils. J Leukoc Biol. 2015;97:1081\u20137.","journal-title":"J Leukoc Biol"},{"key":"1730_CR22","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1136\/annrheumdis-2012-203041","volume":"73","author":"D Lindau","year":"2014","unstructured":"Lindau D, Mussard J, Rabsteyn A, Ribon M, K\u00f6tter I, Igney A, et al. TLR9 independent interferon alpha production by neutrophils on NETosis in response to circulating chromatin, a key lupus autoantigen. Ann Rheum Dis. 2014;73:2199\u2013207.","journal-title":"Ann Rheum Dis"},{"key":"1730_CR23","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1186\/s13075-019-2029-1","volume":"21","author":"N Ruchakorn","year":"2019","unstructured":"Ruchakorn N, Ngamjanyaporn P, Suangtamai T, Kafaksom T, Polpanumas C, Petpisit V, et al. Performance of cytokine models in predicting SLE activity. Arthritis Res Ther. 2019;21:287.","journal-title":"Arthritis Res Ther"},{"key":"1730_CR24","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","volume":"34","author":"T Kawai","year":"2011","unstructured":"Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637\u201350.","journal-title":"Immunity"},{"key":"1730_CR25","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nm0598-615","volume":"4","author":"A Belaaouaj","year":"1998","unstructured":"Belaaouaj A, McCarthy R, Baumann M, et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med. 1998;4:615\u20138.","journal-title":"Nat Med"},{"key":"1730_CR26","doi-asserted-by":"publisher","first-page":"73ra20","DOI":"10.1126\/scitranslmed.3001201","volume":"3","author":"GS Garcia-Romo","year":"2011","unstructured":"Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z, et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med. 2011;3:73ra20.","journal-title":"Sci Transl Med"},{"key":"1730_CR27","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1136\/annrheumdis-2018-213181","volume":"78","author":"E Frangou","year":"2019","unstructured":"Frangou E, Chrysanthopoulou A, Mitsios A, Kambas K, Arelaki S, Angelidou I, et al. REDD1\/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A). Ann Rheum Dis. 2019;78:238\u201348.","journal-title":"Ann Rheum Dis"},{"key":"1730_CR28","doi-asserted-by":"publisher","first-page":"e147671","DOI":"10.1172\/jci.insight.147671","volume":"6","author":"S Georgakis","year":"2021","unstructured":"Georgakis S, Gkirtzimanaki K, Papadaki G, Gakiopoulou H, Drakos E, Eloranta ML, et al. NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-\u03b1 production in patients with SLE. JCI Insight. 2021;6:e147671.","journal-title":"JCI Insight"},{"key":"1730_CR29","doi-asserted-by":"publisher","first-page":"9813","DOI":"10.1073\/pnas.0909927107","volume":"107","author":"A Hakkim","year":"2010","unstructured":"Hakkim A, F\u00fcrnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci U S A. 2010;107:9813\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1730_CR30","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1182\/blood-2015-08-607929","volume":"127","author":"X Sim","year":"2016","unstructured":"Sim X, Poncz M, Gadue P, French DL. Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets. Blood. 2016;127:1227\u201333.","journal-title":"Blood"},{"key":"1730_CR31","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1126\/science.1064890","volume":"294","author":"P Blanco","year":"2001","unstructured":"Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science. 2001;294:1540\u20133.","journal-title":"Science"},{"key":"1730_CR32","doi-asserted-by":"publisher","first-page":"47ra63","DOI":"10.1126\/scitranslmed.3001001","volume":"2","author":"P Duffau","year":"2010","unstructured":"Duffau P, Seneschal J, Nicco C, Richez C, Lazaro E, Douchet I, et al. Platelet CD154 potentiates interferon-alpha secretion by plasmacytoid dendritic cells in systemic lupus erythematosus. Sci Transl Med. 2010;2:47ra63.","journal-title":"Sci Transl Med"},{"key":"1730_CR33","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1007\/s00018-022-04222-4","volume":"79","author":"R Suades","year":"2022","unstructured":"Suades R, Padr\u00f3 T, Vilahur G, Badimon L. Platelet-released extracellular vesicles: the effects of thrombin activation. Cell Mol Life Sci. 2022;79:190.","journal-title":"Cell Mol Life Sci"},{"key":"1730_CR34","doi-asserted-by":"publisher","first-page":"937","DOI":"10.3390\/biom10060937","volume":"10","author":"M Taheri","year":"2020","unstructured":"Taheri M, Eghtedarian R, Dinger ME, Ghafouri-Fard S. Exploring the role of non-coding RNAs in the pathophysiology of systemic Lupus Erythematosus. Biomolecules. 2020;10:937.","journal-title":"Biomolecules"},{"key":"1730_CR35","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1101\/gad.1837609","volume":"23","author":"YS Lee","year":"2009","unstructured":"Lee YS, Shibata Y, Malhotra A, Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009;23:2639\u201349.","journal-title":"Genes Dev"},{"key":"1730_CR36","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13046-021-01836-7","volume":"40","author":"EW Tao","year":"2021","unstructured":"Tao EW, Wang HL, Cheng WY, Liu QQ, Chen YX, Gao QY. A specific tRNA half, 5\u2019tiRNA-His-GTG, responds to hypoxia via the HIF1\u03b1\/ANG axis and promotes colorectal cancer progression by regulating LATS2. J Exp Clin Cancer Res. 2021;40:67.","journal-title":"J Exp Clin Cancer Res"},{"issue":"12","key":"1730_CR37","doi-asserted-by":"publisher","first-page":"e3000982","DOI":"10.1371\/journal.pbio.3000982","volume":"18","author":"K Pawar","year":"2020","unstructured":"Pawar K, Shigematsu M, Sharbati S, Kirino Y. Infection-induced 5\u2032-half molecules of tRNAHisGUG activate toll-like receptor 7. PLOS Biol. 2020;18(12):e3000982.","journal-title":"PLOS Biol"},{"key":"1730_CR38","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1111\/cei.13566","volume":"204","author":"A Paradowska-Gorycka","year":"2021","unstructured":"Paradowska-Gorycka A, Wajda A, Stypinska B, Walczuk E, Rzeszotarska E, Walczyk M, et al. Variety of endosomal TLRs and interferons (IFN-\u03b1, IFN-\u03b2, IFN-\u03b3) expression profiles in patients with SLE, SSc and MCTD. Clin Exp Immunol. 2021;204:49\u201363.","journal-title":"Clin Exp Immunol"},{"key":"1730_CR39","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1084\/jem.20161512","volume":"214","author":"C Lood","year":"2017","unstructured":"Lood C, Arve S, Ledbetter J, Elkon KB. TLR7\/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA. J Exp Med. 2017;214:2103\u201319.","journal-title":"J Exp Med"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-024-01730-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-024-01730-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-024-01730-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T12:01:27Z","timestamp":1720353687000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-024-01730-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,7]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1730"],"URL":"https:\/\/doi.org\/10.1186\/s12964-024-01730-7","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,7]]},"assertion":[{"value":"27 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 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":"This study was conducted in compliance with the Declaration of Helsinki and has been approved by the Institutional Review Board of Taichung Veterans General Hospital (CF21176A). The study methods were carried out in accordance with the approved guidelines and written consent was obtained from all participants.","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 no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"354"}}