综述
ENGLISH ABSTRACT
不同细胞来源外泌体对眼表的作用研究进展
康艺龄
赵少贞 [综述]
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20200419-00271
Recent advances on the role of various cells-derived exosomes in ocular surface
Kang Yiling
Zhao Shaozhen
Authors Info & Affiliations
Kang Yiling
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
Zhao Shaozhen
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
·
DOI: 10.3760/cma.j.cn115989-20200419-00271
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摘要

外泌体是由细胞分泌的一种膜性囊泡,可广泛参与细胞间通讯、抗炎、免疫调节等。眼表相关的外泌体来源细胞有间充质干细胞(MSC)、调节性T细胞(Treg)、未成熟树突状细胞(imDC)和髓源性抑制细胞(MDSC)。不同细胞来源的外泌体通过递送不同的生物分子给受体细胞而发挥作用。MSC来源的外泌体通过抑制T细胞增生、转换巨噬细胞表型、调控辅助性T(Th)细胞分化、上调Treg表达等机制对眼表炎症与免疫相关疾病有积极作用,同时可减少新生血管和炎症反应,培育了一个可促进角膜损伤修复的微环境。Treg来源外泌体内含微小RNA(miRNA)(miR-503、miR-330和miR-9)和诱导型NO合成酶,可通过干扰细胞周期进程,诱导凋亡和其他T细胞分化为Treg表型,抑制T细胞的同种异体排斥反应从而诱导免疫耐受。imDC来源外泌体通过递送miR-682抑制角膜植片免疫排斥。MDSC来源外泌体在体内外促进Treg扩增,抑制活化T细胞的增生和细胞毒性反应,还表达miR-29a-3p和miR-93-5p,可抑制Th1和Th17细胞分化。鉴于上述外泌体的抗炎及免疫抑制作用,本文就其对眼表炎症与免疫相关疾病如角膜损伤、黏多糖贮积症、干眼、干燥综合征和眼部移植物抗宿主病等的研究进行综述。

外泌体;胞外囊泡;间充质干细胞;调节性T细胞;未成熟树突状细胞;髓源性抑制细胞
ABSTRACT

Exosomes are membranous vesicles secreted by cells and can be widely involved in intercellular communication, anti-inflammation, immunoregulation, etc.Mesenchymal stem cell (MSC), regulatory T cell (Treg), immature dendritic cell (imDC) and myeloid-derived suppressor cell (MDSC) are the main ocular surface-related exosomes origins.Exosomes derived from different cells play their roles by delivering different biological molecules to recipient cells.Exosomes derived from MSC play a positive role in ocular surface inflammation and immune-related diseases by inhibiting T cell proliferation, transforming macrophage phenotype, regulating T helper (Th) cell differentiation and up-regulating Treg expression, reduce neovascularization and inflammation, and foster a microenvironment to promote corneal wound healing at the same time.Exosomes derived from Treg contain inducible NO synthase and microRNA (miRNA) including miR-503, miR-330 and miR-9, which can interfere with cell cycle progression, induce apoptosis, induce the differentiation of other T cells into Treg phenotype, inhibit T cell allograft rejection to induce immune tolerance.Exosomes derived from imDC inhibit corneal allograft rejection by delivering miR-682.MDSC-derived exosomes promote Treg expansion in vivo and in vitro, inhibit the proliferation and cytotoxicity of activated T cells, and express miR-29a-3p and miR-93-5p, which can inhibit the differentiation of Th1 and Th17 cells.Given the anti-inflammatory and immunosuppressive effects of exosomes, this paper reviewed the studies on ocular surface inflammation and immune-related diseases such as corneal injury, mucopolysaccharide storage disease, dry eye, Sjögren syndrome and ocular graft-versus-host disease.

Exosomes;Extracellular vesicles;Mesenchymal stem cell;Regulatory T cell;Immature dendritic cell;Myeloid-derived suppressor cell
Zhao Shaozhen, Email: mocdef.aabnis7991zsoahz
引用本文

康艺龄,赵少贞. 不同细胞来源外泌体对眼表的作用研究进展[J]. 中华实验眼科杂志,2022,40(08):766-770.

DOI:10.3760/cma.j.cn115989-20200419-00271

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外泌体是细胞分泌的膜性囊泡,膜上的突起是膜蛋白,与靶向结合有关,内容物主要是脂质、蛋白质和核酸 [ 1 ]。探索不同细胞来源的外泌体功能和特点对不同疾病的诊断和治疗有研究价值。目前,对不同细胞分泌的外泌体作用于眼表疾病的认识还不全面,本文就不同细胞分泌外泌体的特点及其作用于眼表疾病的研究进行综述。
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参考文献
[1]
Pammi Guru KT Sreeja JS Dharmapal D et al. Novel gold nanoparticle-based quick small-exosome isolation technique from serum sample at a low centrifugal force[J/OL]Nanomaterials (Basel) 202212(10)∶1660[2021-12-08]https://pubmed.ncbi.nlm.nih.gov/35630882/. DOI: 10.3390/nano12101660 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Trajkovic K Hsu C Chiantia S et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes[J]Science 2008319(5867)∶12441247. DOI: 10.1126/science.1153124 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Thirumala S Goebel WS Woods EJ . Clinical grade adult stem cell banking[J]Organogenesis 20095(3)∶143154. DOI: 10.4161/org.5.3.9811 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Aghayan HR Goodarzi P Arjmand B GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy[J]Methods Mol Biol 2015128393107. DOI: 10.1007/7651_2014_112 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Jin HJ Bae YK Kim M et al. Comparative analysis of human mesenchymal stem cells from bone marrow,adipose tissue,and umbilical cord blood as sources of cell therapy[J/OL]Int J Mol Sci 201314(9)∶1798618001[2021-12-05]https://pubmed.ncbi.nlm.nih.gov/24005862/. DOI: 10.3390/ijms140917986 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Veréb Z Póliska S Albert R et al. Role of human corneal stroma-derived mesenchymal-like stem cells in corneal immunity and wound healing[J/OL]Sci Rep 2016626227[2021-12-05]https://pubmed.ncbi.nlm.nih.gov/27195722/. DOI: 10.1038/srep26227 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Kureshi AK Funderburgh JL Daniels JT . Human corneal stromal stem cells exhibit survival capacity following isolation from stored organ-culture corneas[J]Invest Ophthalmol Vis Sci 201455(11)∶75837588. DOI: 10.1167/iovs.14-14448 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
刘先宁汪耀朱秀萍人角膜基质间充质干细胞的分离培养及表型鉴定[J]现代检验医学杂志 201934(4)∶28-30,34. DOI: 10.3969/j.issn.1671-7414.2019.04.007 .
返回引文位置Google Scholar
百度学术
万方数据
Liu XN Wang Y Zhu XP et al. Isolation,culture and phenotype identification of human corneal stromal mesenchymal stem cells[J]J Mod Lab Med 201934(4)∶28-30,34. DOI: 10.3969/j.issn.1671-7414.2019.04.007 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[9]
Harrell CR Jovicic N Djonov V et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases[J/OL]Cells 20198(12)∶1605[2021-12-06]https://pubmed.ncbi.nlm.nih.gov/31835680/. DOI: 10.3390/cells8121605 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Samaeekia R Rabiee B Putra I et al. Effect of human corneal mesenchymal stromal cell-derived exosomes on corneal epithelial wound healing[J]Invest Ophthalmol Vis Sci 201859(12)∶51945200. DOI: 10.1167/iovs.18-24803 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Leszczynska A Kulkarni M Ljubimov AV et al. Exosomes from normal and diabetic human corneolimbal keratocytes differentially regulate migration,proliferation and marker expression of limbal epithelial cells[J/OL]Sci Rep 20188(1)∶15173[2021-12-06]https://pubmed.ncbi.nlm.nih.gov/30310159/. DOI: 10.1038/s41598-018-33169-5 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Shen T Zheng QQ Shen J et al. Effects of adipose-derived mesenchymal stem cell exosomes on corneal stromal fibroblast viability and extracellular matrix synthesis[J]Chin Med J (Engl) 2018131(6)∶704712. DOI: 10.4103/0366-6999.226889 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Shen T Zheng Q Luo H et al. Exosomal miR-19a from adipose-derived stem cells suppresses differentiation of corneal keratocytes into myofibroblasts[J]Aging (Albany NY) 202012(5)∶40934110. DOI: 10.18632/aging.102802 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Sahu A Foulsham W Amouzegar A et al. The therapeutic application of mesenchymal stem cells at the ocular surface[J]Ocul Surf 201917(2)∶198207. DOI: 10.1016/j.jtos.2019.01.006 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Shojaati G Khandaker I Funderburgh ML et al. Mesenchymal stem cells reduce corneal fibrosis and inflammation via extracellular vesicle-mediated delivery of miRNA[J]Stem Cells Transl Med 20198(11)∶11921201. DOI: 10.1002/sctm.18-0297 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Oh JY Kim MK Shin MS et al. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury[J]Stem Cells 200826(4)∶10471055. DOI: 10.1634/stemcells.2007-0737 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
陈俊秋黄梁浒间充质干细胞及其外泌体促血管再生的分子机制研究进展[J]中国实验血液学杂志 201826(6)∶18581862. DOI: 10.7534/j.issn.1009-2137.2018.06.047 .
返回引文位置Google Scholar
百度学术
万方数据
Chen JQ Huang LH . Advances of researchs on molecular mechanisms of mesenchymal stem cells and theirexosomes in angiogenesis—review[J]J Exp Hematol 201826(6)∶18581862. DOI: 10.7534/j.issn.1009-2137.2018.06.047 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[18]
Han KY Dugas-Ford J Seiki M et al. Evidence for the involvement of MMP14 in MMP2 processing and recruitment in exosomes of corneal fibroblasts[J]Invest Ophthalmol Vis Sci 201556(9)∶53235329. DOI: 10.1167/iovs.14-14417 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Han KY Chang JH Azar DT . MMP14-containing exosomes cleave VEGFR1 and promote VEGFA-induced migration and proliferation of vascular endothelial cells[J]Invest Ophthalmol Vis Sci 201960(6)∶23212329. DOI: 10.1167/iovs.18-26277 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
McKay TB Hutcheon A Zieske JD et al. Extracellular vesicles secreted by corneal epithelial cells promote myofibroblast differentiation[J/OL]Cells 20209(5)∶1080[2021-12-10]https://pubmed.ncbi.nlm.nih.gov/32357574/. DOI: 10.3390/cells9051080 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Han KY Tran JA Chang JH et al. Potential role of corneal epithelial cell-derived exosomes in corneal wound healing and neovascularization[J/OL]Sci Rep 2017740548[2021-12-10]https://pubmed.ncbi.nlm.nih.gov/28165027/. DOI: 10.1038/srep40548 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
罗丹赵敏角膜移植免疫排斥反应细胞疗法的研究进展[J]中华实验眼科杂志 201735(9)∶848851. DOI: 10.3760/cma.j.issn.2095-0160.2017.09.016 .
返回引文位置Google Scholar
百度学术
万方数据
Luo D Zhao M Recent advances of cellular therapy for corneal graft rejection[J]Chin J Exp Ophthalmol 201735(9)∶848851. DOI: 10.3760/cma.j.issn.2095-0160.2017.09.016 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[23]
Lu X Chu C Liu X et al. High-throughput RNA-sequencing identifies mesenchymal stem cell-induced immunological signature in a rat model of corneal allograft rejection[J/OL]PLoS One 201914(9)∶e0222515[2021-12-11]https://pubmed.ncbi.nlm.nih.gov/31545822/. DOI: 10.1371/journal.pone.0222515 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Murphy N Treacy O Lynch K et al. TNF-α/IL-1β-licensed mesenchymal stromal cells promote corneal allograft survival via myeloid cell-mediated induction of Foxp3 + regulatory T cells in the lung [J]FASEB J 201933(8)∶94049421. DOI: 10.1096/fj.201900047R .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Jia Z Li F Zeng X et al. The effects of local administration of mesenchymal stem cells on rat corneal allograft rejection[J/OL]BMC Ophthalmol 201818(1)∶139[2021-12-11]https://pubmed.ncbi.nlm.nih.gov/29884142/. DOI: 10.1186/s12886-018-0802-6 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
贾喆李斐吕瑛间充质干细胞来源外泌体(MSCs-exo)对大鼠角膜移植排斥反应的抑制作用[J]眼科新进展 201838(11)∶10101013.
返回引文位置Google Scholar
百度学术
万方数据
Jia Z Li F Lyu Y et al. Suppressive effect of exosomes derived from mesenchymal stem cells on keratoplasty rejection[J]Rec Adv Ophthalmol 201838(11)∶10101013.
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[27]
Jia Z Lv Y Zhang W et al. Mesenchymal stem cell derived exosomes-based immunological signature in a rat model of corneal allograft rejection therapy[J/OL]Front Biosci (Landmark Ed) 202227(3)∶86[2021-12-11]https://pubmed.ncbi.nlm.nih.gov/35345318/. DOI: 10.31083/j.fbl2703086 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Coulson-Thomas VJ Caterson B Kao WW . Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis Ⅶ mice[J]Stem Cells 201331(10)∶21162126. DOI: 10.1002/stem.1481 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Craig JP Nichols KK Akpek EK et al. TFOS DEWS Ⅱ definition and classification report[J]Ocul Surf 201715(3)∶276283. DOI: 10.1016/j.jtos.2017.05.008 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
周颖谭钢王甜间充质干细胞外泌体治疗小鼠干眼的疗效评价[J]眼科新进展 201939(10)∶901905.
返回引文位置Google Scholar
百度学术
万方数据
Zhou Y Tan G Wang T et al. Therapeutic effects of mesenchymal stem cells derived exosomes on dry eye mice[J]Rec Adv Ophthalmol 201939(10)∶901905.
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[31]
李娜粘红赵璐人脐带间充质干细胞来源外泌体对兔自身免疫性干眼外周血巨噬细胞的调控[J]中华实验眼科杂志 201937(11)∶854862. DOI: 10.3760/cma.j.issn.2095-0160.2019.11.002 .
返回引文位置Google Scholar
百度学术
万方数据
Li N Nian H Zhao L et al. Regulation of human umbilical cord mesenchymal stem cells derived exosomes on peripheral blood macrophages from rabbit autoimmune dry eye[J]Chin J Exp Ophthalmol 201937(11)∶854862. DOI: 10.3760/cma.j.issn.2095-0160.2019.11.002 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[32]
Dietrich J Roth M König S et al. Analysis of lacrimal gland derived mesenchymal stem cell secretome and its impact on epithelial cell survival[J/OL]Stem Cell Res 201938101477[2021-12-13]https://pubmed.ncbi.nlm.nih.gov/31181482/. DOI: 10.1016/j.scr.2019.101477 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Wang G Li H Long H et al. Exosomes derived from mouse adipose-derived mesenchymal stem cells alleviate benzalkonium chloride-induced mouse dry eye model via inhibiting NLRP3 inflammasome[J]Ophthalmic Res 202265(1)∶4051. DOI: 10.1159/000519458 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Kapsogeorgou EK Abu-Helu RF Moutsopoulos HM et al. Salivary gland epithelial cell exosomes:a source of autoantigenic ribonucleoproteins[J]Arthritis Rheum 200552(5)∶15171521. DOI: 10.1002/art.21005 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Li N Zhao L Wei Y et al. Recent advances of exosomes in immune-mediated eye diseases[J/OL]Stem Cell Res Ther 201910(1)∶278[2021-12-15]https://pubmed.ncbi.nlm.nih.gov/31470892/. DOI: 10.1186/s13287-019-1372-0 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Martínez-Carrasco R Sánchez-Abarca LI Nieto-Gómez C et al. Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD[J]Ocul Surf 201917(2)∶285294. DOI: 10.1016/j.jtos.2019.01.001 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Lai P Chen X Guo L et al. A potent immunomodulatory role of exosomes derived from mesenchymal stromal cells in preventing cGVHD[J/OL]J Hematol Oncol 201811(1)∶135[2021-12-15]https://pubmed.ncbi.nlm.nih.gov/30526632/. DOI: 10.1186/s13045-018-0680-7 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Fujii S Miura Y Fujishiro A et al. Graft-versus-host disease amelioration by human bone marrow mesenchymal stromal/stem cell-derived extracellular vesicles is associated with peripheral preservation of naive T cell populations[J]Stem Cells 201836(3)∶434445. DOI: 10.1002/stem.2759 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
曹启江周奕辰王金岩CD4~+CD25~+Treg细胞分泌外泌体在疾病中作用的研究进展[J]中国免疫学杂志 201834(8)∶1268-1273+1281. DOI: 10.3969/j.issn.1000-484X.2018.08.029 .
返回引文位置Google Scholar
百度学术
万方数据
Cao QJ Zhou YC Wang JY . Immunoregulation and progress of Treg cell-derived exosomes in disease research[J]Chin J Immunol 201834(8)∶1268-1273+1281. DOI: 10.3969/j.issn.1000-484X.2018.08.029 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[40]
边江王婷史伟云调节性T细胞在角膜移植排斥反应中的研究进展[J]国际眼科杂志 201919(1)∶5155. DOI: 10.3980/j.issn.1672-5123.2019.1.10 .
返回引文位置Google Scholar
百度学术
万方数据
Bian J Wang T Shi WY et al. Research progress of regulatory T cells in corneal allograft rejection[J]Int Eye Sci 201919(1)∶5155. DOI: 10.3980/j.issn.1672-5123.2019.1.10 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[41]
Chen L Huang H Zhang W et al. Exosomes derived from T regulatory cells suppress CD8+cytotoxic T lymphocyte proliferation and prolong liver allograft survival[J]Med Sci Monit 20192548774884. DOI: 10.12659/MSM.917058 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Aiello S Rocchetta F Longaretti L et al. Extracellular vesicles derived from T regulatory cells suppress T cell proliferation and prolong allograft survival[J/OL]Sci Rep 20177(1)∶11518[2021-12-15]https://pubmed.ncbi.nlm.nih.gov/28912528/. DOI: 10.1038/s41598-017-08617-3 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
李佳李雪孙建华IL-10基因修饰的未成熟树突状细胞在大鼠角膜移植排斥反应中的作用[J]国际眼科杂志 201616(8)∶14391443. DOI: 10.3980/j.issn.1672-5123.2016.8.09 .
返回引文位置Google Scholar
百度学术
万方数据
Li J Li X Sun JH et al. Role and its mechanism of immature dendritic cells with IL-10 gene modified in rats after keratoplasty[J]Int Eye Sci 201616(8)∶14391443. DOI: 10.3980/j.issn.1672-5123.2016.8.09 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[44]
Pang XL Wang ZG Liu L et al. Immature dendritic cells derived exosomes promotes immune tolerance by regulating T cell differentiation in renal transplantation[J]Aging (Albany NY) 201911(20)∶89118924. DOI: 10.18632/aging.102346 .
返回引文位置Google Scholar
百度学术
万方数据
[45]
Zhang W Li J Qi G et al. Myeloid-derived suppressor cells in transplantation:the dawn of cell therapy[J/OL]J Transl Med 201816(1)∶19[2021-12-16]https://pubmed.ncbi.nlm.nih.gov/29378596/. DOI: 10.1186/s12967-018-1395-9 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
He Y Bei J Zeng H et al. The roles of sepsis-induced myeloid derived suppressor cells in mice corneal,skin and combined transplantation[J]Transpl Immunol 201634813. DOI: 10.1016/j.trim.2015.12.003 .
返回引文位置Google Scholar
百度学术
万方数据
[47]
He Y Wang B Jia B et al. Effects of adoptive transferring different sources of myeloid-derived suppressor cells in mice corneal transplant survival[J]Transplantation 201599(10)∶21022108. DOI: 10.1097/TP.0000000000000749 .
返回引文位置Google Scholar
百度学术
万方数据
[48]
Zöller M Zhao K Kutlu N et al. Immunoregulatory effects of myeloid-derived suppressor cell exosomes in mouse model of autoimmune alopecia areata[J/OL]Front Immunol 201891279[2021-12-18]https://pubmed.ncbi.nlm.nih.gov/29951053/. DOI: 10.3389/fimmu.2018.01279 .
返回引文位置Google Scholar
百度学术
万方数据
[49]
Zhu D Tian J Wu X et al. G-MDSC-derived exosomes attenuate collagen-induced arthritis by impairing Th1 and Th17 cell responses[J/OL]Biochim Biophys Acta Mol Basis Dis 20191865(12)∶165540[2021-12-18]https://pubmed.ncbi.nlm.nih.gov/31470074/. DOI: 10.1016/j.bbadis.2019.165540 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
赵少贞,Email: mocdef.aabnis7991zsoahz
B
所有作者均声明不存在利益冲突
C
国家自然科学基金项目 (81970769、81770890)
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