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| 1 | Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese显示文摘Alzheimer's disease is the most common neurodegenerative disease,and has a high level of genetic heritability and population heterogeneity.In this study,we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease,followed by independent validation,imaging analysis and function characterization.We identified an exome-wide significant rare missense variant rs3792646(p.K420Q)in the C7 gene in the discovery stage(P=1.09×10^(-6),odds ratio=7.853)and confirmed the association in different cohorts and a combined sample(1615 cases and 2832 controls,P_(combined)=2.99×10^(-7),odds ratio=1.930).The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood,thus resulting in an earlier age of disease onset.Overexpression of the mutant p.K420Q disturbed cell viability,immune activation and β-amyloid processing.Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons.These findings suggested that C7 is a novel risk gene for Alzheimer’s disease in Han Chinese. | Deng-Feng Zhang Yu Fan Min Xu Guihong Wang Dong Wang Jin Li Li-Li Kong Hejiang Zhou Rongcan Luo Rui Bi Yong Wu Guo-Dong Li Ming Li Xiong-Jian Luo Hong-Yan Jiang Liwen Tan Chunjiu Zhong Yiru Fang Chen Zhang Nengyin Sheng Tianzi Jiang Yong-Gang Yao | 2019 | National Science Review2019，6，2： | 6 |
| 2 | Recovery of fertility in quinestrol-treated or diethylstilbestroltreated mice:Implications for rodent management显示文摘Fertility control is an alternative strategy to traditional culling for the management of rodent pests.Previous studies have demonstrated that quinestrol is a potential contraceptive for male rodents,but the recovery of fertility in quinestrol-treated rodents has not been evaluated.This study used C57BL/6J mice to evaluate the recovery rate of male fertility after the administration of quinestrol.Diethylstilbestrol(DES),a non-steroid estrogenic compound,was used for comparison.Different groups of mice were treated with 1 mg/kg quinestrol,1 mg/kg DES,or castor oil separately for 7 days.These mice were then killed on days 8,22 and 50 respectively.Our results indicated that the weight of epididymides and seminal vesicles decreased significantly on days 8 and 22 in quinestrol/DES-treated mice,with extensive histological changes in the seminiferous tubules.Sperm concentrations in the cauda epididymal fluid were significantly reduced on days 8 and 22 in both quinestrol and DES treatment groups and on day 50 for the DES,but not the quinestrol group.Further analysis revealed that DES-treated mice exhibited a higher proportion of abnormal sperm accumulation in the epididymis,indicating that the normal sperm transportation to the cauda epididymis was blocked.Our results indicate that the anti-fertility effects on male mice given quinestrol were of shorter duration than for those receiving DES at the dose of 1 mg/kg body weight. | Ming LIU Rongcan LUO Hao WANG Guangming CAO Yanling WANG | 2017 | Integrative Zoology2017，12，3： | 1 |
| 3 | A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease,impairs lysosomal function,and facilitates amyloid-p pathology and cognitive decline显示文摘Alzheimer’s disease(AD)is characterized by progressive synaptic dysfunction,neuronal death,and brain atrophy,with amyloid-p(Ap)plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue,which all lead to loss of cognitive function.Pathogenic mutations in the well-known AD causal genes including APP,PSEN1,and PSEN2 impair a variety of pathways,including protein processing,axonal transport,and metabolic homeostasis.Here we identified a missense variant rs117916664(c.896T>C,p.Asn299Ser[p.N299S])of the acetyl-CoA acyltransferase 1(ACM1)gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort.Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity,impairing lysosomal function,and aggravating the Ap pathology and neuronal loss,which finally caused cognitive impairment in a murine model.Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis. | Rongcan Luo Yu Fan Jing Yang Maosen Ye Deng-Feng Zhang Kun Guo Xiao Li Rui Bi Min Xu Lu-Xiu Yang Yu Li Xiaoqian Ran Hong-Yan Jiang Chen Zhang Liwen Tan Nengyin Sheng Yong-Gang Yao | 2021 | Signal Transduction and Targeted Therapy2021，6，9： | 1 |
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