{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:30:27Z","timestamp":1763706627694,"version":"3.37.3"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2020GGA019","2020CXA015"],"award-info":[{"award-number":["2020GGA019","2020CXA015"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01419"],"award-info":[{"award-number":["2021J01419"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Funds for the innovation of science and Technology of Fujian province","award":["2020Y9152"],"award-info":[{"award-number":["2020Y9152"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>mTORC1 (mechanistic target of rapamycin complex 1) is associated with lymphoma progression. Oncogenic RRAGC (Rag guanosine triphosphatase C) mutations identified in patients with follicular lymphoma facilitate the interaction between Raptor (regulatory protein associated with mTOR) and Rag GTPase. It promotes the activation of mTORC1 and accelerates lymphomagenesis. Cardamonin inhibits mTORC1 by decreasing the protein level of Raptor. In the present study, we investigated the inhibitory effect and possible mechanism of action of cardamonin in RRAGC-mutant lymphoma. This could provide a precise targeted therapy for lymphoma with RRAGC mutations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Cell viability was measured using a cell counting kit-8 (CCK-8) assay. Protein expression and phosphorylation levels were determined using western blotting. The interactions of mTOR and Raptor with RagC were determined by co-immunoprecipitation. Cells overexpressing RagC wild-type (RagC<jats:sup>WT<\/jats:sup>) and RagC Thr90Asn (RagC<jats:sup>T90N<\/jats:sup>) were generated by lentiviral infection. Raptor knockdown was performed by lentivirus-mediated shRNA transduction. The in vivo anti-tumour effect of cardamonin was assessed in a xenograft model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Cardamonin disrupted mTOR complex interactions by decreasing Raptor protein levels. RagC<jats:sup>T90N<\/jats:sup> overexpression via lentiviral infection increased cell proliferation and mTORC1 activation. The viability and tumour growth rate of RagC<jats:sup>T90N<\/jats:sup>-mutant cells were more sensitive to cardamonin treatment than those of normal and RagC<jats:sup>WT<\/jats:sup> cells. Cardamonin also exhibited a stronger inhibitory effect on the phosphorylation of mTOR and p70 S6 kinase 1 in RagC<jats:sup>T90N<\/jats:sup>-mutant cells. Raptor knockdown abolishes the inhibitory effects of cardamonin on mTOR. An in vivo xenograft model demonstrated that the RagC<jats:sup>T90N<\/jats:sup>-mutant showed significantly higher sensitivity to cardamonin treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Cardamonin exerts selective therapeutic effects on RagC<jats:sup>T90N<\/jats:sup>-mutant cells. Cardamonin can serve as a drug for individualised therapy for follicular lymphoma with RRAGC mutations.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12906-023-04166-7","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T02:01:42Z","timestamp":1695693702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Raptor mediates the selective inhibitory effect of cardamonin on RRAGC-mutant B cell lymphoma"],"prefix":"10.1186","volume":"23","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanting","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huajiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jintuo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiguang","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daohua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"issue":"12","key":"4166_CR1","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1002\/ajh.26737","volume":"97","author":"E Jacobsen","year":"2022","unstructured":"Jacobsen E. Follicular lymphoma: 2023 update on diagnosis and management. Am J Hematol. 2022;97(12):1638\u201351.","journal-title":"Am J Hematol"},{"issue":"1","key":"4166_CR2","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s11899-021-00617-5","volume":"16","author":"LJ Nastoupil","year":"2021","unstructured":"Nastoupil LJ. When to use targeted therapy for the treatment of follicular lymphoma. Curr Hematol Malig Rep. 2021;16(1):45\u201351.","journal-title":"Curr Hematol Malig Rep"},{"issue":"12","key":"4166_CR3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s11864-021-00909-1","volume":"22","author":"LA Leslie","year":"2021","unstructured":"Leslie LA. Novel therapies for follicular lymphoma and other indolent Non-Hodgkin Lymphomas. Curr Treat Options Oncol. 2021;22(12):111.","journal-title":"Curr Treat Options Oncol"},{"issue":"4","key":"4166_CR4","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","volume":"21","author":"GY Liu","year":"2020","unstructured":"Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183\u2013203.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"2","key":"4166_CR5","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.cell.2017.03.035","volume":"169","author":"RA Saxton","year":"2017","unstructured":"Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017;169(2):361\u201371.","journal-title":"Cell"},{"issue":"3","key":"4166_CR6","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1152\/physrev.00026.2020","volume":"101","author":"A Szwed","year":"2021","unstructured":"Szwed A, Kim E, Jacinto E. Regulation and metabolic functions of mTORC1 and mTORC2. Physiol Rev. 2021;101(3):1371\u2013426.","journal-title":"Physiol Rev"},{"issue":"11","key":"4166_CR7","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1016\/j.cell.2022.04.013","volume":"185","author":"S Battaglioni","year":"2022","unstructured":"Battaglioni S, Benjamin D, Walchli M, Maier T, Hall MN. mTOR substrate phosphorylation in growth control. Cell. 2022;185(11):1814\u201336.","journal-title":"Cell"},{"issue":"6","key":"4166_CR8","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1158\/1535-7163.MCT-11-0723","volume":"11","author":"JC Montero","year":"2012","unstructured":"Montero JC, Chen X, Ocana A, Pandiella A. Predominance of mTORC1 over mTORC2 in the regulation of proliferation of ovarian cancer cells: therapeutic implications. Mol Cancer Ther. 2012;11(6):1342\u201352.","journal-title":"Mol Cancer Ther"},{"issue":"9","key":"4166_CR9","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1038\/s41556-022-00981-1","volume":"24","author":"N Alesi","year":"2022","unstructured":"Alesi N, Henske EP. Keeping up with the rag GTPases. Nat Cell Biol. 2022;24(9):1330\u20131.","journal-title":"Nat Cell Biol"},{"issue":"9","key":"4166_CR10","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/s41556-022-00976-y","volume":"24","author":"P Gollwitzer","year":"2022","unstructured":"Gollwitzer P, Grutzmacher N, Wilhelm S, Kummel D, Demetriades C. A rag GTPase dimer code defines the regulation of mTORC1 by amino acids. Nat Cell Biol. 2022;24(9):1394\u2013406.","journal-title":"Nat Cell Biol"},{"issue":"2","key":"4166_CR11","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/ng.3473","volume":"48","author":"J Okosun","year":"2016","unstructured":"Okosun J, Wolfson RL, Wang J, Araf S, Wilkins L, Castellano BM, et al. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. Nat Genet. 2016;48(2):183\u20138.","journal-title":"Nat Genet"},{"issue":"21","key":"4166_CR12","doi-asserted-by":"publisher","first-page":"5383","DOI":"10.1158\/1078-0432.CCR-16-0609","volume":"22","author":"ZX Ying","year":"2016","unstructured":"Ying ZX, Jin M, Peterson LF, Bernard D, Saiya-Cork K, Yildiz M, et al. Recurrent mutations in the MTOR Regulator RRAGC in Follicular Lymphoma. Clin Cancer Res. 2016;22(21):5383\u201393.","journal-title":"Clin Cancer Res"},{"issue":"6462","key":"4166_CR13","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1126\/science.aax3939","volume":"366","author":"M Anandapadamanaban","year":"2019","unstructured":"Anandapadamanaban M, Masson GR, Perisic O, Berndt A, Kaufman J, Johnson CM, et al. Architecture of human rag GTPase heterodimers and their complex with mTORC1. Science. 2019;366(6462):203\u201310.","journal-title":"Science"},{"issue":"6464","key":"4166_CR14","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1126\/science.aay0166","volume":"366","author":"KB Rogala","year":"2019","unstructured":"Rogala KB, Gu X, Kedir JF, Abu-Remaileh M, Bianchi LF, Bottino AMS, et al. Structural basis for the docking of mTORC1 on the lysosomal surface. Science. 2019;366(6464):468\u201375.","journal-title":"Science"},{"issue":"8","key":"4166_CR15","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/s42255-019-0098-8","volume":"1","author":"A Ortega-Molina","year":"2019","unstructured":"Ortega-Molina A, Deleyto-Seldas N, Carreras J, Sanz A, Lebrero-Fernandez C, Menendez C, et al. Oncogenic rag GTPase signaling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR. Nat Metab. 2019;1(8):775\u201389.","journal-title":"Nat Metab"},{"issue":"5","key":"4166_CR16","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/ajh.24671","volume":"92","author":"NN Bennani","year":"2017","unstructured":"Bennani NN, LaPlant BR, Ansell SM, Habermann TM, Inwards DJ, Micallef IN, et al. Efficacy of the oral mTORC1 inhibitor everolimus in relapsed or refractory indolent lymphoma. Am J Hematol. 2017;92(5):448\u201353.","journal-title":"Am J Hematol"},{"issue":"3","key":"4166_CR17","first-page":"383","volume":"7","author":"SH Hare","year":"2017","unstructured":"Hare SH, Harvey AJ. mTOR function and therapeutic targeting in breast cancer. Am J Cancer Res. 2017;7(3):383\u2013404.","journal-title":"Am J Cancer Res"},{"issue":"7606","key":"4166_CR18","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nature17963","volume":"534","author":"VS Rodrik-Outmezguine","year":"2016","unstructured":"Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, et al. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016;534(7606):272\u20136.","journal-title":"Nature"},{"issue":"4","key":"4166_CR19","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1055\/s-0028-1097682","volume":"29","author":"C Bheemasankara Rao","year":"1976","unstructured":"Bheemasankara Rao C, Namosiva Rao T, Suryaprakasam S. Cardamonin and alpinetin from the seeds of Amomum subulatum. Planta Med. 1976;29(4):391\u20132.","journal-title":"Planta Med"},{"key":"4166_CR20","doi-asserted-by":"publisher","first-page":"117591","DOI":"10.1016\/j.lfs.2020.117591","volume":"250","author":"J Nawaz","year":"2020","unstructured":"Nawaz J, Rasul A, Shah MA, Hussain G, Riaz A, Sarfraz I, et al. Cardamonin: a new player to fight cancer via multiple cancer signaling pathways. Life Sci. 2020;250:117591.","journal-title":"Life Sci"},{"key":"4166_CR21","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.omto.2022.06.009","volume":"26","author":"H Chen","year":"2022","unstructured":"Chen H, Huang S, Niu P, Zhu Y, Zhou J, Jiang L, et al. Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition. Mol Ther Oncolytics. 2022;26:175\u201388.","journal-title":"Mol Ther Oncolytics"},{"issue":"1\u20132","key":"4166_CR22","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.lfs.2014.01.066","volume":"99","author":"Y Tang","year":"2014","unstructured":"Tang Y, Fang Q, Shi D, Niu P, Chen Y, Deng J. mTOR inhibition of cardamonin on antiproliferation of A549 cells is involved in a FKBP12 independent fashion. Life Sci. 2014;99(1\u20132):44\u201351.","journal-title":"Life Sci"},{"issue":"1","key":"4166_CR23","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s12906-018-2380-9","volume":"18","author":"D Shi","year":"2018","unstructured":"Shi D, Zhao D, Niu P, Zhu Y, Zhou J, Chen H. Glycolysis inhibition via mTOR suppression is a key step in cardamonin-induced autophagy in SKOV3 cells. BMC Complement Altern Med. 2018;18(1):317.","journal-title":"BMC Complement Altern Med"},{"key":"4166_CR24","doi-asserted-by":"publisher","first-page":"757","DOI":"10.2147\/OTT.S155065","volume":"11","author":"D Shi","year":"2018","unstructured":"Shi D, Zhu Y, Niu P, Zhou J, Chen H. Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3 cells. Onco Targets Ther. 2018;11:757\u201367.","journal-title":"Onco Targets Ther"},{"issue":"14","key":"4166_CR25","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","volume":"14","author":"DD Sarbassov","year":"2004","unstructured":"Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004;14(14):1296\u2013302.","journal-title":"Curr Biol"},{"issue":"2","key":"4166_CR26","first-page":"97","volume":"36","author":"KE Cahill","year":"2022","unstructured":"Cahill KE, Smith SM. Follicular lymphoma: a focus on current and emerging therapies. Oncol (Williston Park). 2022;36(2):97\u2013106.","journal-title":"Oncol (Williston Park)"},{"issue":"2","key":"4166_CR27","doi-asserted-by":"publisher","first-page":"109372","DOI":"10.1016\/j.celrep.2021.109372","volume":"36","author":"A Ortega-Molina","year":"2021","unstructured":"Ortega-Molina A, Lebrero-Fernandez C, Sanz A, Deleyto-Seldas N, Plata-Gomez AB, Menendez C, et al. Inhibition of rag GTPase signaling in mice suppresses B cell responses and lymphomagenesis with minimal detrimental trade-offs. Cell Rep. 2021;36(2):109372.","journal-title":"Cell Rep"},{"issue":"10","key":"4166_CR28","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1038\/aps.2015.68","volume":"36","author":"LH Meng","year":"2015","unstructured":"Meng LH, Zheng XF. Toward rapamycin analog (rapalog)-based precision cancer therapy. Acta Pharmacol Sin. 2015;36(10):1163\u20139.","journal-title":"Acta Pharmacol Sin"},{"issue":"31","key":"4166_CR29","doi-asserted-by":"publisher","first-page":"4740","DOI":"10.1200\/JCO.2010.29.2813","volume":"28","author":"SM Smith","year":"2010","unstructured":"Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, et al. Temsirolimus has activity in non-mantle cell non-hodgkin\u2019s lymphoma subtypes: the University of Chicago phase II consortium. J Clin Oncol. 2010;28(31):4740\u20136.","journal-title":"J Clin Oncol"},{"key":"4166_CR30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40164-018-0103-z","volume":"7","author":"PB Johnston","year":"2018","unstructured":"Johnston PB, Pinter-Brown LC, Warsi G, White K, Ramchandren R. Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma. Exp Hematol Oncol. 2018;7:12.","journal-title":"Exp Hematol Oncol"},{"issue":"4","key":"4166_CR31","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s12185-010-0707-5","volume":"92","author":"K Tobinai","year":"2010","unstructured":"Tobinai K, Ogura M, Maruyama D, Uchida T, Uike N, Choi I, et al. Phase I study of the oral mammalian target of rapamycin inhibitor everolimus (RAD001) in japanese patients with relapsed or refractory non-hodgkin lymphoma. Int J Hematol. 2010;92(4):563\u201370.","journal-title":"Int J Hematol"},{"issue":"1","key":"4166_CR32","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.pathol.2019.09.010","volume":"52","author":"C Randall","year":"2020","unstructured":"Randall C, Fedoriw Y. Pathology and diagnosis of follicular lymphoma and related entities. Pathology. 2020;52(1):30\u20139.","journal-title":"Pathology"},{"key":"4166_CR33","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/ajh.26888","volume":"98","author":"SF Huntington","year":"2023","unstructured":"Huntington SF, Schuster SJ, Ding W, Koehler AB, Brander DM, Rosenthal AC, et al. DTRMWXHS-12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed\/refractory lymphomas: an open-label, multicenter, phase 1a\/1b study. Am J Hematol. 2023;98:739\u201349.","journal-title":"Am J Hematol"},{"issue":"21","key":"4166_CR34","doi-asserted-by":"publisher","first-page":"5579","DOI":"10.1158\/1078-0432.CCR-20-1215","volume":"26","author":"F Janku","year":"2020","unstructured":"Janku F, Park H, Call SG, Madwani K, Oki Y, Subbiah V, et al. Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in patients with relapsed refractory Hodgkin Lymphoma. Clin Cancer Res. 2020;26(21):5579\u201387.","journal-title":"Clin Cancer Res"},{"issue":"6","key":"4166_CR35","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1182\/blood-2003-07-2469","volume":"103","author":"A Egle","year":"2004","unstructured":"Egle A, Harris AW, Bath ML, O\u2019Reilly L, Cory S. VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia. Blood. 2004;103(6):2276\u201383.","journal-title":"Blood"},{"issue":"2","key":"4166_CR36","doi-asserted-by":"publisher","first-page":"3874","DOI":"10.3390\/ijms14023874","volume":"14","author":"N Alqurashi","year":"2013","unstructured":"Alqurashi N, Hashimi SM, Wei MQ. Chemical inhibitors and microRNAs (miRNA) targeting the mammalian target of Rapamycin (mTOR) pathway: potential for Novel Anticancer therapeutics. Int J Mol Sci. 2013;14(2):3874\u2013900.","journal-title":"Int J Mol Sci"},{"issue":"16","key":"4166_CR37","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.3390\/molecules27165295","volume":"27","author":"B Mao","year":"2022","unstructured":"Mao B, Zhang Q, Ma L, Zhao DS, Zhao P, Yan P. Overview of research into mTOR inhibitors. Molecules. 2022;27(16):5295.","journal-title":"Molecules"},{"issue":"5","key":"4166_CR38","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.pharep.2018.04.005","volume":"70","author":"D Shi","year":"2018","unstructured":"Shi D, Niu P, Heng X, Chen L, Zhu Y, Zhou J. Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3 cells. Pharmacol Rep. 2018;70(5):908\u201316.","journal-title":"Pharmacol Rep"},{"issue":"4","key":"4166_CR39","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s00210-020-01986-z","volume":"394","author":"Y Zhu","year":"2021","unstructured":"Zhu Y, Zhou J, Niu P, Chen H, Shi D. Cardamonin inhibits cell proliferation by caspase-mediated cleavage of Raptor. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(4):809\u201317.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"3","key":"4166_CR40","first-page":"1399","volume":"21","author":"P Niu","year":"2020","unstructured":"Niu P, Li J, Chen H, Zhu Y, Zhou J, Shi D. Anti\u2013proliferative effect of cardamonin on mTOR inhibitor\u2013resistant cancer cells. Mol Med Rep. 2020;21(3):1399\u2013407.","journal-title":"Mol Med Rep"},{"issue":"8","key":"4166_CR41","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1007\/s00439-016-1685-3","volume":"135","author":"PA Long","year":"2016","unstructured":"Long PA, Zimmermann MT, Kim M, Evans JM, Xu X, Olson TM. De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy. Hum Genet. 2016;135(8):909\u201317.","journal-title":"Hum Genet"},{"issue":"3","key":"4166_CR42","first-page":"11","volume":"4","author":"PA Long","year":"2017","unstructured":"Long PA, Evans JM, Olson TM. Diagnostic yield of whole exome sequencing in Pediatric Dilated Cardiomyopathy. J Cardiovasc Dev Dis. 2017;4(3):11.","journal-title":"J Cardiovasc Dev Dis"},{"issue":"11","key":"4166_CR43","doi-asserted-by":"publisher","first-page":"5494","DOI":"10.3390\/ijms22115494","volume":"22","author":"M Kim","year":"2021","unstructured":"Kim M, Lu L, Dvornikov AV, Ma X, Ding Y, Zhu P, et al. TFEB overexpression, not mTOR inhibition, ameliorates RagC(S75Y) cardiomyopathy. Int J Mol Sci. 2021;22(11):5494.","journal-title":"Int J Mol Sci"},{"issue":"7948","key":"4166_CR44","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41586-022-05652-7","volume":"614","author":"Z Cui","year":"2023","unstructured":"Cui Z, Napolitano G, de Araujo MEG, Esposito A, Monfregola J, Huber LA, et al. Structure of the lysosomal mTORC1-TFEB-Rag-ragulator megacomplex. Nature. 2023;614(7948):572\u20139.","journal-title":"Nature"},{"issue":"9","key":"4166_CR45","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1038\/s41556-022-00977-x","volume":"24","author":"G Figlia","year":"2022","unstructured":"Figlia G, Muller S, Hagenston AM, Kleber S, Roiuk M, Quast JP, et al. Brain-enriched RagB isoforms regulate the dynamics of mTORC1 activity through GATOR1 inhibition. Nat Cell Biol. 2022;24(9):1407\u201321.","journal-title":"Nat Cell Biol"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-023-04166-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12906-023-04166-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-023-04166-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T20:03:49Z","timestamp":1700424229000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-023-04166-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4166"],"URL":"https:\/\/doi.org\/10.1186\/s12906-023-04166-7","relation":{},"ISSN":["2662-7671"],"issn-type":[{"type":"electronic","value":"2662-7671"}],"subject":[],"published":{"date-parts":[[2023,9,26]]},"assertion":[{"value":"14 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 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 animal works were approved by the Ethics Committee of Fujian Maternity and Child Health Hospital (Ethical approval No.: 2022KYLLD03088). All experiments were performed in accordance with relevant guidelines and regulations. We confirmed that the study was carried out in compliance with the ARRIVE guidelines.","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":"336"}}