{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T04:12:43Z","timestamp":1794370363557,"version":"4.9.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":15,"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":["81671207"],"award-info":[{"award-number":["81671207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Proteom"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of IL-1\u03b2, TNF-\u03b1, and KLK6 in the CH group was higher than that in the control group. After knockdown of KLK6 expression using small-interfering RNA (siRNA), the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. Following siRNA interference KLK6 expression, 5681 differentially expressed genes (DEGs) were identified in transcriptome profile. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after the interference of KLK6 expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12014-021-09335-9","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T09:02:29Z","timestamp":1639645349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Proteomics and functional study reveal kallikrein-6 enhances communicating hydrocephalus"],"prefix":"10.1186","volume":"18","author":[{"given":"Lei","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6247-7862","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fance","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"9335_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/2045-8118-11-13","volume":"11","author":"LR Drewes","year":"2014","unstructured":"Drewes LR, Jones HC, Keep RF. News from the editors of fluids and barriers of the CNS. Fluids Barriers CNS. 2014;11:13. https:\/\/doi.org\/10.1186\/2045-8118-11-13.","journal-title":"Fluids Barriers CNS"},{"issue":"5","key":"9335_CR2","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1159\/000346119","volume":"69","author":"TC Yang","year":"2013","unstructured":"Yang TC, Chang CH, Liu YT, Chen YL, Tu PH, Chen HC. Predictors of shunt-dependent chronic hydrocephalus after aneurysmal subarachnoid haemorrhage. Eur Neurol. 2013;69(5):296\u2013303. https:\/\/doi.org\/10.1159\/000346119.","journal-title":"Eur Neurol"},{"issue":"9","key":"9335_CR3","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1007\/s10072-016-2589-7","volume":"37","author":"H Xu","year":"2016","unstructured":"Xu H. New concept of the pathogenesis and therapeutic orientation of acquired communicating hydrocephalus. Neurol Sci. 2016;37(9):1387\u201391. https:\/\/doi.org\/10.1007\/s10072-016-2589-7.","journal-title":"Neurol Sci"},{"issue":"Pt 9","key":"9335_CR4","doi-asserted-by":"publisher","first-page":"2842","DOI":"10.1093\/brain\/awt203","volume":"136","author":"H Botfield","year":"2013","unstructured":"Botfield H, Gonzalez AM, Abdullah O, Skjolding AD, Berry M, McAllister JP 2nd, Logan A. Decorin prevents the development of juvenile communicating hydrocephalus. Brain. 2013;136(Pt 9):2842\u201358. https:\/\/doi.org\/10.1093\/brain\/awt203.","journal-title":"Brain"},{"issue":"1","key":"9335_CR5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.canlet.2006.12.018","volume":"249","author":"M Paliouras","year":"2007","unstructured":"Paliouras M, Borgono C, Diamandis EP. Human tissue kallikreins: the cancer biomarker family. Cancer Lett. 2007;249(1):61\u201379. https:\/\/doi.org\/10.1016\/j.canlet.2006.12.018.","journal-title":"Cancer Lett"},{"issue":"1","key":"9335_CR6","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1002\/1878-0261.12587","volume":"14","author":"T Kryza","year":"2020","unstructured":"Kryza T, Bock N, Lovell S, Rockstroh A, Lehman ML, Lesner A, Panchadsaram J, Silva LM, et al. The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer. Mol Oncol. 2020;14(1):105\u201328. https:\/\/doi.org\/10.1002\/1878-0261.12587.","journal-title":"Mol Oncol"},{"issue":"10","key":"9335_CR7","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nrurol.2016.161","volume":"13","author":"CM Muytjens","year":"2016","unstructured":"Muytjens CM, Vasiliou SK, Oikonomopoulou K, Prassas I, Diamandis EP. Putative functions of tissue kallikrein-related peptidases in vaginal fluid. Nat Rev Urol. 2016;13(10):596\u2013607. https:\/\/doi.org\/10.1038\/nrurol.2016.161.","journal-title":"Nat Rev Urol"},{"issue":"4","key":"9335_CR8","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1046\/j.1440-1819.2000.00731.x","volume":"54","author":"K Ogawa","year":"2000","unstructured":"Ogawa K, Yamada T, Tsujioka Y, Taguchi J, Takahashi M, Tsuboi Y, Fujino Y, Nakajima M, et al. Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer\u2019s disease and Parkinson\u2019s disease. Psychiatry Clin Neurosci. 2000;54(4):419\u201326. https:\/\/doi.org\/10.1046\/j.1440-1819.2000.00731.x.","journal-title":"Psychiatry Clin Neurosci"},{"issue":"9","key":"9335_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045676","volume":"7","author":"E Martinez-Morillo","year":"2012","unstructured":"Martinez-Morillo E, Diamandis A, Romaschin AD, Diamandis EP. Kallikrein 6 as a serum prognostic marker in patients with aneurysmal subarachnoid hemorrhage. PLoS ONE. 2012;7(9): e45676. https:\/\/doi.org\/10.1371\/journal.pone.0045676.","journal-title":"PLoS ONE"},{"issue":"2","key":"9335_CR10","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1515\/CCLM.2011.750","volume":"50","author":"J Bayani","year":"2011","unstructured":"Bayani J, Diamandis EP. The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6). Clin Chem Lab Med. 2011;50(2):211\u201333. https:\/\/doi.org\/10.1515\/CCLM.2011.750.","journal-title":"Clin Chem Lab Med"},{"key":"9335_CR11","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/978-3-030-04615-6_15","volume":"127","author":"H Suzuki","year":"2020","unstructured":"Suzuki H, Fujimoto M, Kawakita F, Liu L, Nakano F, Nishikawa H, Okada T, Imanaka-Yoshida K, et al. Toll-like receptor 4 and tenascin-C signaling in cerebral vasospasm and brain injuries after subarachnoid hemorrhage. Acta Neurochir Suppl. 2020;127:91\u20136. https:\/\/doi.org\/10.1007\/978-3-030-04615-6_15.","journal-title":"Acta Neurochir Suppl"},{"key":"9335_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.113057","volume":"322","author":"F Kawakita","year":"2019","unstructured":"Kawakita F, Kanamaru H, Asada R, Suzuki H. Potential roles of matricellular proteins in stroke. Exp Neurol. 2019;322: 113057. https:\/\/doi.org\/10.1016\/j.expneurol.2019.113057.","journal-title":"Exp Neurol"},{"issue":"10","key":"9335_CR13","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1515\/cclm-2019-0034","volume":"57","author":"K Minta","year":"2019","unstructured":"Minta K, Cullen NC, Nimer FA, Thelin EP, Piehl F, Clarin M, Tullberg M, Jeppsson A, et al. Dynamics of extracellular matrix proteins in cerebrospinal fluid and serum and their relation to clinical outcome in human traumatic brain injury. Clin Chem Lab Med. 2019;57(10):1565\u201373. https:\/\/doi.org\/10.1515\/cclm-2019-0034.","journal-title":"Clin Chem Lab Med"},{"key":"9335_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234215","author":"W Wan","year":"2019","unstructured":"Wan W, Wang L, Chen X, Zhu S, Shang W, Xiao G, Zhang LK. A subcellular quantitative proteomic analysis of herpes simplex virus type 1-infected HEK 293T cells. Molecules. 2019. https:\/\/doi.org\/10.3390\/molecules24234215.","journal-title":"Molecules"},{"issue":"3","key":"9335_CR15","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1093\/jnen\/62.3.292","volume":"62","author":"SS Cherian","year":"2003","unstructured":"Cherian SS, Love S, Silver IA, Porter HJ, Whitelaw AG, Thoresen M. Posthemorrhagic ventricular dilation in the neonate: development and characterization of a rat model. J Neuropathol Exp Neurol. 2003;62(3):292\u2013303. https:\/\/doi.org\/10.1093\/jnen\/62.3.292.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"1\u20132","key":"9335_CR16","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.brainresbull.2010.06.009","volume":"83","author":"X Chen","year":"2010","unstructured":"Chen X, Huang X, Li B, Zhao Z, Jiang L, Huang C, Lu Y. Changes in neural dendrites and synapses in rat somatosensory cortex following neonatal post-hemorrhagic hydrocephalus. Brain Res Bull. 2010;83(1\u20132):44\u20138. https:\/\/doi.org\/10.1016\/j.brainresbull.2010.06.009.","journal-title":"Brain Res Bull"},{"issue":"27","key":"9335_CR17","doi-asserted-by":"publisher","first-page":"24562","DOI":"10.1074\/jbc.M202392200","volume":"277","author":"MJ Bernett","year":"2002","unstructured":"Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M. Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem. 2002;277(27):24562\u201370. https:\/\/doi.org\/10.1074\/jbc.M202392200.","journal-title":"J Biol Chem"},{"issue":"7","key":"9335_CR18","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1179\/016164101101199243","volume":"23","author":"T Takizawa","year":"2001","unstructured":"Takizawa T, Tada T, Kitazawa K, Tanaka Y, Hongo K, Kameko M, Uemura KI. Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res. 2001;23(7):724\u201330. https:\/\/doi.org\/10.1179\/016164101101199243.","journal-title":"Neurol Res"},{"key":"9335_CR19","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005751","author":"M Mayford","year":"2012","unstructured":"Mayford M, Siegelbaum SA, Kandel ER. Synapses and memory storage. Cold Spring Harb Perspect Biol. 2012. https:\/\/doi.org\/10.1101\/cshperspect.a005751.","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"10","key":"9335_CR20","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1016\/j.psyneuen.2010.05.006","volume":"35","author":"C Garcia-Caceres","year":"2010","unstructured":"Garcia-Caceres C, Lagunas N, Calmarza-Font I, Azcoitia I, Diz-Chaves Y, Garcia-Segura LM, Baquedano E, Frago LM, et al. Gender differences in the long-term effects of chronic prenatal stress on the HPA axis and hypothalamic structure in rats. Psychoneuroendocrinology. 2010;35(10):1525\u201335. https:\/\/doi.org\/10.1016\/j.psyneuen.2010.05.006.","journal-title":"Psychoneuroendocrinology"},{"key":"9335_CR21","doi-asserted-by":"publisher","first-page":"175883591984123","DOI":"10.1177\/1758835919841233","volume":"11","author":"TYS Le Large","year":"2019","unstructured":"Le Large TYS, El Hassouni B, Funel N, Kok B, Piersma SR, Pham TV, Olive KP, Kazemier G, et al. Proteomic analysis of gemcitabine-resistant pancreatic cancer cells reveals that microtubule-associated protein 2 upregulation associates with taxane treatment. Ther Adv Med Oncol. 2019;11:1758835919841233. https:\/\/doi.org\/10.1177\/1758835919841233.","journal-title":"Ther Adv Med Oncol"},{"issue":"3","key":"9335_CR22","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1007\/s00441-014-1978-6","volume":"358","author":"JW Shim","year":"2014","unstructured":"Shim JW, Sandlund J, Madsen JR. VEGF: a potential target for hydrocephalus. Cell Tissue Res. 2014;358(3):667\u201383. https:\/\/doi.org\/10.1007\/s00441-014-1978-6.","journal-title":"Cell Tissue Res"},{"issue":"2","key":"9335_CR23","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3171\/PED\/2008\/1\/2\/131","volume":"1","author":"TD Simon","year":"2008","unstructured":"Simon TD, Riva-Cambrin J, Srivastava R, Bratton SL, Dean JM, Kestle JR. Hydrocephalus clinical research N: hospital care for children with hydrocephalus in the United States: utilization, charges, comorbidities, and deaths. J Neurosurg Pediatr. 2008;1(2):131\u20137. https:\/\/doi.org\/10.3171\/PED\/2008\/1\/2\/131.","journal-title":"J Neurosurg Pediatr"},{"key":"9335_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.113115","volume":"324","author":"Y Munster","year":"2020","unstructured":"Munster Y, Keyvani K, Herring A. Inhibition of excessive kallikrein-8 improves neuroplasticity in Alzheimer\u2019s disease mouse model. Exp Neurol. 2020;324: 113115. https:\/\/doi.org\/10.1016\/j.expneurol.2019.113115.","journal-title":"Exp Neurol"},{"key":"9335_CR25","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708184","author":"K Kidana","year":"2018","unstructured":"Kidana K, Tatebe T, Ito K, Hara N, Kakita A, Saito T, Takatori S, Ouchi Y, et al. Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer\u2019s disease model mice. EMBO Mol Med. 2018. https:\/\/doi.org\/10.15252\/emmm.201708184.","journal-title":"EMBO Mol Med"},{"key":"9335_CR26","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s40035-019-0168-6","volume":"8","author":"O Goldhardt","year":"2019","unstructured":"Goldhardt O, Warnhoff I, Yakushev I, Begcevic I, Forstl H, Magdolen V, Soosaipillai A, Diamandis E, et al. Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer\u2019s disease and associated with CSF-TAU and FDG-PET. Transl Neurodegener. 2019;8:25. https:\/\/doi.org\/10.1186\/s40035-019-0168-6.","journal-title":"Transl Neurodegener"},{"issue":"8","key":"9335_CR27","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1373\/clinchem.2007.088104","volume":"53","author":"JL Shaw","year":"2007","unstructured":"Shaw JL, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem. 2007;53(8):1423\u201332. https:\/\/doi.org\/10.1373\/clinchem.2007.088104.","journal-title":"Clin Chem"},{"issue":"5","key":"9335_CR28","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1111\/j.1460-9568.2006.05021.x","volume":"24","author":"IA Scarisbrick","year":"2006","unstructured":"Scarisbrick IA, Sabharwal P, Cruz H, Larsen N, Vandell AG, Blaber SI, Ameenuddin S, Papke LM, et al. Dynamic role of kallikrein 6 in traumatic spinal cord injury. Eur J Neurosci. 2006;24(5):1457\u201369. https:\/\/doi.org\/10.1111\/j.1460-9568.2006.05021.x.","journal-title":"Eur J Neurosci"},{"issue":"8","key":"9335_CR29","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/S0009-9120(00)00185-5","volume":"33","author":"EP Diamandis","year":"2000","unstructured":"Diamandis EP, Yousef GM, Petraki C, Soosaipillai AR. Human kallikrein 6 as a biomarker of Alzheimer\u2019s disease. Clin Biochem. 2000;33(8):663\u20137.","journal-title":"Clin Biochem"},{"key":"9335_CR30","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjaa058","author":"Y Wu","year":"2020","unstructured":"Wu Y, Lv X, Wang H, Qian K, Ding J, Wang J, Hua S, Sun T, et al. Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons. J Mol Cell Biol. 2020. https:\/\/doi.org\/10.1093\/jmcb\/mjaa058.","journal-title":"J Mol Cell Biol"},{"key":"9335_CR31","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.cellsig.2017.01.018","volume":"32","author":"Z Liu","year":"2017","unstructured":"Liu Z, Xiao T, Peng X, Li G, Hu F. APPLs: More than just adiponectin receptor binding proteins. Cell Signal. 2017;32:76\u201384. https:\/\/doi.org\/10.1016\/j.cellsig.2017.01.018.","journal-title":"Cell Signal"},{"issue":"2","key":"9335_CR32","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.ydbio.2011.03.008","volume":"353","author":"EM McNeill","year":"2011","unstructured":"McNeill EM, Klockner-Bormann M, Roesler EC, Talton LE, Moechars D, Clagett-Dame M. Nav2 hypomorphic mutant mice are ataxic and exhibit abnormalities in cerebellar development. Dev Biol. 2011;353(2):331\u201343. https:\/\/doi.org\/10.1016\/j.ydbio.2011.03.008.","journal-title":"Dev Biol"},{"key":"9335_CR33","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.brainres.2019.06.004","volume":"1719","author":"IS Piras","year":"2019","unstructured":"Piras IS, Krate J, Delvaux E, Nolz J, De Both MD, Mastroeni DF, Serrano GE, Sue LI, et al. Association of AEBP1 and NRN1 RNA expression with Alzheimer\u2019s disease and neurofibrillary tangle density in middle temporal gyrus. Brain Res. 2019;1719:217\u201324. https:\/\/doi.org\/10.1016\/j.brainres.2019.06.004.","journal-title":"Brain Res"},{"issue":"1","key":"9335_CR34","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s12031-020-01627-3","volume":"71","author":"T Huang","year":"2021","unstructured":"Huang T, Li H, Zhang S, Liu F, Wang D, Xu J. Nrn1 overexpression attenuates retinal ganglion cell apoptosis, promotes axonal regeneration, and improves visual function following optic nerve crush in rats. J Mol Neurosci. 2021;71(1):66\u201379. https:\/\/doi.org\/10.1007\/s12031-020-01627-3.","journal-title":"J Mol Neurosci"}],"container-title":["Clinical Proteomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12014-021-09335-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12014-021-09335-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12014-021-09335-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T09:02:31Z","timestamp":1639645351000},"score":1,"resource":{"primary":{"URL":"https:\/\/clinicalproteomicsjournal.biomedcentral.com\/articles\/10.1186\/s12014-021-09335-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["9335"],"URL":"https:\/\/doi.org\/10.1186\/s12014-021-09335-9","relation":{},"ISSN":["1542-6416","1559-0275"],"issn-type":[{"value":"1542-6416","type":"print"},{"value":"1559-0275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"18 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 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 human and rat study protocol was adhere to the principles of the Declaration of Helsinki and approved by the Institutional Ethics Committee of The Affiliated Sixth People\u2019s Hospital, Shanghai Jiaotong University. All participants were fully informed and signed written informed consent in this study. All efforts were made to minimize rat suffering.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"30"}}