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| 1 | Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility显示文摘Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF. | Lijun Ding Guijun Yan Bin Wang Lu Xu Yan Gu Tong Ru Xiaoying Cui Lei Lei Jingyu Liu Xiaoqiang Sheng Bin Wang Chunxue Zhang Yanjun Yang Ruiwei Jiang Jianjun Zhou Na Kong Feifei Lu Huaijun Zhou Yannan Zhao Bing Chen Yali Hu Jianwu Dai Haixiang Sun | 2018 | Science China(Life Sciences)2018，61，12： | 43 |
| 2 | Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome显示文摘Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS. | Guangfeng Zhao Yun Cao Xianghong Zhu Xiaoqiu Tang Lijun Ding Haixiang Sun Juan Li Xinan Li Chenyan Dai Tong Ru Hui Zhu Jingjie Lu Caimei Lin Jingmei Wang Guijun Yan Huiyan Wang Lei Wang Yimin Dai Bin Wang Ruotian Li Jianwu Dai Yan Zhou Yali Hu | 2017 | Science China(Life Sciences)2017，60，4： | 39 |
| 3 | Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells显示文摘体的房间能由定义因素是进导致的 pluripotent 干细胞(iPSCs ) 的 reprogrammed。reprogramming 的低效率和 oncogenes 和病毒的向量的 genomic 集成限制了 iPSCs 的潜在的申请。这里,我们报导那锂(李) ,药过去常对待心情混乱,极大地从老鼠提高 iPSC 产生胚胎的成纤维细胞和人的脐的静脉 endothelial 房间。李与(Oct4 ) 或二个因素(OS 或好) 便于 iPSC 产生。支持 reprogramming 上的李的效果仅仅部分取决于它的主要目标 GSK3β。不同于另外的 GSK3β禁止者,李不仅增加 Nanog 的表示,而且提高 Nanog 的 transcriptional 活动。我们也发现李由经由 LSD1 的 downregulation 支持 epigenetic 修正施加它的效果, H3K4 特定的 histone demethylase。将 LSD1 击倒部分在提高 reprogramming 模仿李的效果。我们的结果不仅提供一个直接方法改进 iPSC 产生效率,而且为体的房间 reprogramming 作为一个批评调节的人识别了 histone demethylase。 | Quan Wang Xinxiu Xu Jun Li Jing Liu Haifeng Gu Ru Zhang Jiekai Chen Yin Kuang Jian Fei Cong Jiang Ping Wang Duanqing Pei Sheng Ding Xin Xie | 2011 | Cell Research2011，21，10： | 23 |
| 4 | Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice显示文摘Objective To determine the ability of grape seed proanthocyanidin extract(GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution(control); arsenic trioxide(ATO; 4 mg/kg); GSPE(400 mg/kg); ATO+GSPE(100 mg/kg); ATO+GSPE(200 mg/kg) and ATO+GSPE(400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor(erythroid-derived 2)-like 2(Nrf2), heme oxygenase 1(HO1), glutathione S-transferase(GST), NAD(P)H dehydrogenase, and quinone 1(NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase(SOD), glutathione(GSH), total antioxidative capability(T-AOC), malondialdehyde(MDA), 8-hydroxydeoxyguanosine(8-OHd G), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of m RNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity. | LI Shu Gang DING Yu Song NIU Qiang XU Shang Zhi PANG Li Juan MA Ru Lin JING Ming Xia FENG Gang Ling LIU Jia Ming GUO Shu Xia | 2015 | Biomedical and Environmental Sciences2015，28，4： | 14 |
| 5 | Short-term effect of Salvia miltiorhiza in treating rat acetic acid chronic gastric ulcer and long-term effect in preventing recurrence显示文摘ShorttermefectofSalviamiltiorhizaintreatingrataceticacidchronicgastriculcerandlongtermefectinpreventingrecurenceWANGGuoZho... | Wang, GZ Ru, X Ding, LH Li, HQ | 1998 | World Journal of Gastroenterology1998，4，2： | 8 |
| 6 | Surrogate production of genome-edited sperm from a different subfamily by spermatogonial stem cell transplantation显示文摘The surrogate reproduction technique,such as inter-specific spermatogonial stem cells(SSCs)transplantation(SSCT),provides a powerful tool for production of gametes derived from endangered species or those with desirable traits.However,generation of genome-edited gametes from a different species or production of gametes from a phylogenetically distant species such as from a different subfamily,by SSCT,has not succeeded.Here,using two small cyprinid fishes from different subfamilies,Chinese rare minnow(gobiocypris rarus,for brief:Gr)and zebrafish(danio rerio),we successfully obtained Gr-derived genome-edited sperm in zebrafish by an optimized SSCT procedure.The transplanted Gr SSCs supported the host gonadal development and underwent normal spermatogenesis,resulting in a reconstructed fertile testis containing Gr spermatids and zebrafish testicular somatic cells.Interestingly,the surrogate spermatozoa resembled those of host zebrafish but not donor Gr in morphology and swimming behavior.When pou5f3 and chd knockout Gr SSCs were transplanted,Gr-derived genome-edited sperm was successfully produced in zebrafish.This is the first report demonstrating surrogate production of gametes from a different subfamily by SSCT,and surrogate production of genome-edited gametes from another species as well.This method is feasible to be applied to future breeding of commercial fish and livestock. | Fenghua Zhang Yongkang Hao Xianmei Li Yi Li Ding Ye Ru Zhang Xiaosi Wang Mudan He Houpeng Wang Zuoyan Zhu Yonghua Sun | 2022 | Science China(Life Sciences)2022，65，5： | 7 |
| 7 | Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage显示文摘Asparaginyl endopeptidase (AEP ) 是有为在 P1 地点的天门冬素残余的偏爱的 endo/lysosomal 半胱氨酸 endopeptidase 并且在像使用费的受体 3/7/9 的成熟起一个重要作用。AEP 被知道为催化激活在酸的 pH 经历 autoproteolytic 成熟。这里,我们描述 AEP 酶原的水晶结构和 AEP 的成熟形式。在 AEP 和 caspases 之间的结构的比较在关键残余的作文并且在催化机制揭示了类似。Mutagenesis 研究作为为肽底层的劈开是必要的残余识别了 N44, R46, H150, E189, C191, S217/S218 和 D233。在成熟期间, AEP 的帽子领域的 autoproteolytic 劈开在核心领域上开创存取到活跃地点。出人意料地,一个中间的 autoproteolytic 成熟阶段被发现在近似 pH 4.5 在哪个部分激活的 AEP 能被颠倒回到它的酶原形式。这个唯一的特征被 AEP pH4.5 (AEP 在 pH 被成熟 4.5 并且在 pH 结晶 8.5 ) ,在哪个破肽契约被重新绑扎,结构被转变回到它的酶原形式。另外, AEP 禁止者 cystatin C 能被充分激活的 AEP 消化,但是不能被激活的组织蛋白酶消化。因此,我们第一次证明 cystatins 可以为活跃地点通过底层竞争调整 AEP 的活动。 | Lixia Zhao Tian Hua Christopher Crowley Heng Ru Xiangmin Ni Neil Shaw Lianying Jiao Wei Ding Lu Qu Li-Wei Hung Wei Huang Lei Liu Keqiang Ye Songying Ouyang Genhong Cheng Zhi-Jie Liu | 2014 | Cell Research2014，24，3： | 6 |
| 8 | Asymptotic Properties of the Maximum Likelihood Estimate in Generalized Linear Models with Stochastic Regressors显示文摘为概括线性模型(GLM ) ,以防 regressors 是随机的并且有不同分布,参数的最大的可能性的估计(MLE ) 的 asymptotic 性质被学习。在合理条件下面,我们证明弱、强壮的一致性和 asymptotic 规度。关键词概括了线性模型 - 一致性 - 中国自然科学基础支持的 Asymptotic 规度先生(2000 ) 题目分类 62J12 | Jie Li DING Xi Ru CHEN | 2006 | Acta Mathematica Sinica,English Series2006，22，6： | 6 |
| 9 | Gender differences are associated with the clinical features of systemic lupus erythematosus显示文摘 | DING Yan HE Jing GUO Jian-ping DAI Yi-jun LI Chun FENG Min LI Ru LI Zhan-guo | 2012 | Chinese Medical Journal2012，，14： | 5 |
| 10 | Structural basis for termination of AIM2-mediated signaling by p202显示文摘 | Heng Ru Xiangmin Ni LixiaZhao Christopher Crowle Wei Ding Li-Wei Hung Neil Shaw Genhong Cheng Zhi-Jie Liu | 2013 | Cell Research2013，23，6： | 5 |
| 11 | Studies of the intestinal absorption of the alkaloids in the Wu-tou decoction combined with different incompatible medicinal herbs in a Caco-2 cell culture system using UPLC-MS/MS显示文摘In this study,seven alkaloids were detected in Wu-tou decoction using ultra performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS').The aim of this study was to investigate the effect of Fritillariae Cirrhosae Bulbus,Fritillariae Thunbergii Bulbils,Pinelliae Rhizoma in different ratios with Wu-tou decoction(2:1,1:1,1:2) by measuring the therapeutic effects in Wu-tou decoction of main seven alkaloids including benzoylaconitine(BA),benzoylmesaconitine(BM),benzoylhypaconitine(BH),hypaconitine(HA),fuziline(FU),niaolin(NE) and deoxyaconitine(DA).The permeability of aconitum alkaloids extract through a Caco-2 cell monolayer was analyzed in the absence and presence of Fritillariae Cirrhosae Bulbus,Fritillariae Thunbergii Bulbus,and Pinelliae Rhizoma,respectively.The results showed that Pinelliae Rhizoma could reduce the absorption of the alkaloids and increase the excretion of the alkaloids,which would attenuate the therapeutic effects of Wu-tou decoction.Therefore.Pinelliae Rhizoma is an incompatible herb of Wu-tou decoction because of the inhibition of the absorption of alkaloids in the intestine.And that Fritillariae Cirrhosae Bulbus and Fritillariae Thunbergii Bulbus showed the effects to improve the permeability of the alkaloids in Wu-tou decoction.These effects of these two herbs were similar,but the former was stronger than the latter,which most likely is clue to the fact that the compositions of these two traditional Chinese medicines are similar.The in vitro data suggests that the compounds such as fritillary presented in alkaloids in the formula maybe improve the therapeutic function caused by the increased bioavailability of alkaloids in intestine. | Hong Kan Wen-Yue Jiang Ru Ding Zhong-Ying Liu Zi-Feng Pi Zhi-Qiang Liu | 2015 | Chinese Chemical Letters2015，26，5： | 5 |
| 12 | Outcomes of percutaneous coronary intervention in patients ≥ 75 years: one-center study in a Chinese patient group显示文摘ObjectiveTo 调查临床并且病人 ≥ 的 perioperative 特征;75 经历经皮的冠的干预(一种总线标准) 并且从 2011 年 12 月经历了一种总线标准到 2013 年 11 月的连续题目被划分在这特定的病人 group.Methods1,035 评估与短期的一种总线标准以后的死亡有关的风险因素成四个范畴:(1 ) 有稳定的咽峡炎(SA ) 的病人 ≥75 年(n = 58 ) ;(2 ) 有 SA < 的病人;75 年(n = 218 ) ;(3 ) 有急性冠的症候群(交流) 的病人 ≥75 年(n = 155 ) ;(4 ) 有交流 < 的病人;75 年(n = 604 ) 。multivariable 逻辑回归分析被进行在病人 ≥ 检测六月的死亡的风险因素;75 年经历了一种总线标准。临床的 comorbidities,在里面医院生物化学的指示物, perioperative 数据,在里面医院和六月的结果与更年轻的组,一起在四 groups.ResultsCompared 之中被分析并且比较病人 ≥75 年是更可能的有高血压,中风的历史,长期的妨碍的肺的疾病,外部脉管的疾病,心脏性的吃惊和恶意的心律不齐,并且他们与相对更低的重量,血红素,白朊, triglyceride,更高的 creatinine,尿酸,脲氮和 pro-BNP 进入医院。左主要动脉损害,多容器,钙化的损害,长期完全吸藏也是更可能的在老组被看。Univariate 分析揭示了那年龄 ≥在承认,紧急情况一种总线标准,优先的击和长期的肾疾病的 85 年,心脏性的吃惊或严重心律不齐与在老病人 ≥ 的六月的死亡有关;75 年经历了一种总线标准。Multivariable 逻辑回归证明在承认,长期的肾疾病和优先的击的心脏性的吃惊或严重心律不齐是在老病人 ≥ 预言六月的死亡的独立风险因素;75 年经历了 PCI.ConclusionsOur 数据的人,显示出那与在 75 年下面的病人相比,老病人(≥75 年) 经历了一种总线标准的人,有经常伴有 multi-comorbidities, severer 承认条件和复杂冠的损害的死亡,和更多的相对更高的风险。因素和更多强烈地在乎的风险的更好的评估应该被带去病人 ≥75 年经历了一种总线标准治疗减少复杂并发症。 | Peng-Fei CHEN Dan-Ning WANG Kan CHEN Chun LIANG Yu-Sheng RENG Jing YANG Ru DING Jacob Blackwell De-Ning LIAO | 2015 | Journal of Geriatric Cardiology2015，12，6： | 4 |
| 13 | Studies on the intestinal absorption of the alkaloids in the Gancaofuzi decoction in a Caco-2 cell culture system by UPLC–MS/MS analysis显示文摘In this study, the Caco-2 cell monolayer model was used to research the characteristic absorption and efflux of five diterpenoid alkaloids in Gancaofuzi decoction. An ultra performance liquid chromatography coupled with tandem mass spectrometry(UPLC–MS/MS) method was developed for the determination of the simulated intestinal transport of five diterpenoid alkaloids with reserpine as internal standard. The use of the apparent permeability coefficient(Papp) and efflux rate(Er) was instituted to evaluate the intestinal absorption of the alkaloids. Transport of the five alkaloids in Caco-2cell monolayer model was observed to better understand whether the intestinal absorption of alkaloids was influenced by the compatibility of four herbs in Gancaofuzi decoction. The results show that the Papp values of the five diterpenoid alkaloids were all more than 1 * 10^(-6)cm/s, confirming that the processes of permeability were valid. The flux of the alkaloids was time-dependent, and the intestinal absorption mechanism of the five alkaloids was mainly based on passive transport. The compatibility of Heishunpian, Baizhu, Guizhi and Gancao can reduce the intestinal absorption of alkaloids, especially the most toxic hypaconitine, and the attenuated effect of mixed herbal water extracts was better than that of different herbs' water extracts combination. The results prove that compatibility of four herbs in Gancaofuzi decoction is rational. | Ru Ding Yong Jian Hong Kan Zhong-Ying Liu Shu Liu Zhi-Qiang Liu Jun Zhou | 2016 | Chinese Chemical Letters2016，27，6： | 3 |
| 14 | Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs显示文摘An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system.Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport.Induced-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB modeling.Here, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 X.cm2±230 X.cm2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 X.cm2 to 4185 X.cm2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB. | Yuan Li Xueying Sun Houfu Liu Liang Huang Guofeng Meng Yu Ding Wenji Su Jiaqi Lu Sophie Gong Georg C.Terstappen Ru Zhang Wandong Zhang | 2019 | Neuroscience Bulletin2019，35，6： | 3 |
| 15 | Circadian locomotor output cycles kaput accelerates atherosclerotic plaque formation by upregulating plasminogen activator inhibitor-1 expression显示文摘 | Qixia Jiang Hua Liu Shengyun Wang Jiamei Wang Yehua Tang Zhiqing He Feng Wu Zhigang Huang Xiaoliang Cong Ru Ding Chun Liang | 2018 | Acta Biochimica et Biophysica Sinica2018，50，9： | 3 |
| 16 | First total synthesis of a naturally occurring nucleoside disulfide:9-(5'-Deoxy-5'-thio-β-D-xylofuranosyl)adenine disulfide显示文摘A naturally occurring nucleoside disulfide,9-(5'-deoxy-5'-thio-β-D-xylofuranosyl)adenine disulfide,was first synthesized from D-xylose over 7 steps in 20%overall yield.The key step involved Vorbriiggen glycosylation of silylated N^6-benzoyladenine with xylose diacetate moiety. | Hai Xin Ding Ling Cui Da Ru Chun Yang Ban Peng Cao Qi Sun Qiang Xiao | 2012 | Chinese Chemical Letters2012，23，9： | 2 |
| 17 | Two new isoflavonoids from the rhizomes of Belamcanda chinensis显示文摘Two new isoflavonoids, 6-methoxy-5,7,8,4’-tetrahydryoxyisoflavone (1) and 4’-methoxy -5,6-dihydroxyisoflavone-7-O-β-D-glucopyranoside (2), were isolated from the rhizomes of Belamcanda chinensis (L.) DC. Their structures were elucidated by extensive spectroscopic evidence including ID NMR, 2D NMR, MS and IR spectra. | Zhi Jun Song Fan Luo Yan Zhou Bin Ru Bai Shu Lin Peng Li Sheng Ding | 2007 | Chinese Chemical Letters2007，18，6： | 2 |
| 18 | Fighting age-related orthopedic diseases: focusing on ferroptosis显示文摘Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis,particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies. | Qin Ru Yusheng Li Wenqing Xie Yilan Ding Lin Chen Guodong Xu Yuxiang Wu Fudi Wang | 2023 | Bone Research2023，11，1： | 2 |
| 19 | The Bidirectional Effects of Arsenic on miRNA-21: A Systematic Review and Meta-analysis显示文摘Objective Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer. Methods We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21. Results Low-dose arsenic exposure(≤ 5 μmol/L) can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3(pSTAT3) expression, and decrease programmed cell death protein 4(PDCD4) and protein sprouty homolog 1(Spry1) expression. High-dose arsenic exposure(> 5 μmol/L), can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure(≤ 24 h) can increase miRNA-21 and pS TAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure(> 24 h) can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes. Conclusion Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1. | LIU Jia Qing NIU Qing HU Yun Hua LI Yu WANG Hai Xia XU Shang Zhi DING Yu Song LI Shu Gang MA Ru Lin | 2018 | Biomedical and Environmental Sciences2018，31，9： | 2 |
| 20 | EMC10 governs male fertility via maintaining sperm ion balance显示文摘Infertility is a severe public health problem worldwide that prevails up to 15% in reproductive-age couples,and male infertility accounts for half of total infertility.Studies on genetically modified animal models have identifed lots of genes involved in the pathogenesis of male infertility.The underlying causes,however,remain largely unclear.In this study,we provide evidence that EMCIO,one subunit of endoplasmic reticulum (ER)membrane protein complex (EMC),is required for male fertility.EMC10 is significantly decreased in spermatozoa from patients with asthenozoospermia and positively associated with human sperm motility. Male mice lacking Emc10 gene are completely sterile.Emc10-null spermatozoa exhibit multiple defects including abnormal morphology,decreased motility,impaired capacitation,and impotency of acrosome reaction,thereby which are incapable of fertilizing intact or ZP-free oocytes.However,intracytoplasmic sperm injection could rescue this defect caused by EMC10 deletion. Mechanistically,EMC10 deficiency leads to inactivation of Na/K-ATPase,in turn giving rise to an increased level of intraceltutar Na^+ in spermatozoa,which contributes to decreased sperm motility and abnormal morphology.Other mechanistic investigations demonstrate that the absence of EMC10 results in a reduction of HCO3^- entry and subsequent decreases of both cAMP-dependent protein kinase A substrate phosphorylation and protein tyrosine phosphorytation.These data demonstrate that EMC10 is indispensable to mate fertility via maintaining sperm ion balance of Na^+ and HCO3^-,and also suggest that EMC10 is a promising biomarker for male fertility and a potential pharmaceutical target to treat male infertility. | Yuchuan Zhou Fei Wu Man Zhang Zuquan Xiong Qianqian Yin Yanfei Ru Huijuan Shi Jinsong Li Shanhua Mao Yanliang Li Xinyi Cao Renming Hu Chong Wee Liew Qiang Ding Xuanchun Wang Yonglian Zhang | 2018 | Journal of Molecular Cell Biology2018，10，6： | 2 |
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