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| 1 | CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys显示文摘Dear Editor,PINK1 mutations cause autosomal recessive and early-onset Parkinson’s disease(PD)with selective neurodegeneration.Unfortunately,current PINK1 knockout(KO)mouse1,2 and pig models3,4 are unable to recapitulate the selective and overt neurodegeneration seen in PD patients.Furthermore,endogenous Pink1 in the mouse brain is expressed at very low levels and can only be detected via immunoprecipitation,5 meaning that PINK1’s function in the mammalian brain needs to be assessed using larger animals that are closer to humans.We previously used CRISPR/Cas9 to target the monkey gene in one-cell stage embryos.6 Using the same approach,we designed two gRNAs to target exon 2(T1)and exon 4(T2),which encode a kinase domain in the PINK1 gene of rhesus monkeys(Fig.1a).CRISPR/Cas9 and PINK1 gRNAs were injected into one-cell stage rhesus monkey embryos.A T7E1 assay and sequencing of PCR products from the injected embryos showed high efficiency(61.5%)in targeting PINK1(Fig.1b and Supplementary information,Fig.S1).Transfer of 87 embryos to 28 surrogate rhesus monkeys resulted in 11 pregnancies(39.2%)(Fig.1b).Eleven fetuses developed to term and were born naturally.Of these live monkeys,eight carried PINK1 mutations(M),and three were wild type(WT).However,three mutant monkeys(M1,M3 and M4)were newborn triplets that struggled to survive and died 3-4 days after birth.One WT newborn monkey also died after a difficult labor.Another mutant monkey(M2)died 7 days after birth without noticeable warning signs or symptoms.The other three mutant monkeys(M6,M7 and M8)have lived for three years;M5,however,reduced its food intake and showed weakness at the age of 1.5 years,and died 30 days after anesthesia for MRI examination. | Weili Yang Yunbo Liu Zhuchi Tu Chong Xiao Sen Yan Xishan Ma Xiangyu Guo Xiusheng Chen Peng Yin Zhengyi Yang Su Yang Tianzi Jiang Shihua Li Chuan Qin Xiao-Jiang Li | 2019 | Cell Research2019，29，4： | 12 |
| 2 | PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis显示文摘In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1.Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains.CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology.Importantly,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival.Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD. | Weili Yang Xiangyu Guo Zhuchi Tu Xiusheng Chen Rui Han Yanting Liu Sen Yan Qi Wang Zhifu Wang Xianxian Zhao Yunpeng Zhang Xin Xiong Huiming Yang Peng Yin Huida Wan Xingxing Chen Jifeng Guo Xiao-Xin Yan Lujian Liao Shihua Li Xiao-Jiang Li | 2022 | Protein & Cell2022，13，1： | 3 |
| 3 | Expression,mutationand deletion of p16 gene in gastric carcinoma显示文摘 | HE Xiusheng SU Qi CHEN Zhuchu | 2001 | World Journal of Gastroenterology2001，7，： | 1 |
| 4 | Occurrence of antimicro- bials in the final effluents of wastewater treatment plants in Canada 显示文摘 | Miao Xiusheng Bishay F Chen Mei | 2004 | Environmental Science & Technology2004，38，13： | 1 |
| 5 | High-yield cultivation technology of Laiyang taro显示文摘 | Chen Xiusheng | 1994 | Shangdong Agricultural Science1994，，2： | 1 |
| 6 | Occurrence of antimicrobials in the final effiuents of wastewater treatment plants in Canada 显示文摘 | MIAO Xiusheng BISHAY Farida CHEN Mei | 2004 | Environ Sci Technol2004，38，13： | 1 |
| 7 | Occurrence ofantimicrobials in the final effluents of wastewater treatment plants inCanada显示文摘 | MIAO Xiusheng BISHAY F CHEN Mei | 2004 | Environ Sci Technol2004，38，13： | 1 |
| 8 | Recent progress in all-inorganic metal halide nanostructured perovskites:Materials design,optical properties,and application显示文摘Low-dimensional all-inorganic metal halide perovskite(AIMHP)materials,as a new class of nanomaterials,hold great promise for various optoelectronic devices.In the past few years,tremendous progress has been achieved in the development of efficient and stable AIMHP nanomaterials for optical property studies and related applications.Here,we offer a critical overview on the unique merits and the state-of-the-art design of AIMHP using different composition strategies.Then,the effects of material compositions,dimensionality,morphologies and structures on optical properties are summarized.We also comprehensively present recent advances in the development AIMHP nanomaterials for practical applications including solar cells,light-emitting diodes,lasers and photodetectors.Lastly,the critical challenges and future opportunities in this emerging field are highlighted. | Lianzhen Cao Xia Liu Yingde Li Xiusheng Li Lena Du Shengyao Chen Shenlong Zhao Cong Wang | 2021 | Frontiers of physics2021，16，3： | 1 |
| 9 | Occurrence ofantimicrobials in the final effluents of wastewater treatment plants inCanada显示文摘 | MIAO Xiusheng BISHAY F CHEN Mei | 2004 | Environ Sci Technol2004，38，13： | 1 |
| 10 | MUTYH is a potential prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma显示文摘Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the second adenomatous polyposis-related gene,MUTYH,which encodes a DNA gly-cosylase,has been observed in its contribution to oxidative DNA damage repair.Abnormal expression of MUTYH can reduce cell survival rate.Therefore,this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.Materials and methods:Using The Cancer Genome Atlas(TCGA)data,we analyzed the prognostic value of MUTYH in HCC.We used logistic regression,Wilcoxon signed-rank test,and KruskaleWallis test to examine MUTYH expression concerning clinical-pathologic characteristics.Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC.The enrichment analysis(GSEA)was used to determine the critical pathways associated with MUTYH.The single-sample gene set enrichment analysis(ssGSEA)was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.Results:The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that all differentially expressed genes(DEGs)between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction,cell cycle,oocyte meiosis,gap junction,and DNA replication.Group analysis revealed the signals of their open access.The neuron system,M phase,DNA repair,Rho GTPase effector,and cell cycle checkpoints were significantly enriched.ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells,NK cells,and T helper cells.Moreover,a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells(DCs)and cytotoxic cells.Conclusions:MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues.The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC. | Fan Yang Qinghai Lian Beibei Ni Xiusheng Qiu Yizhan He Xiaoguang Zou Fangping He Wenjie Chen | 2022 | Liver Research2022，6，4： | 0 |
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