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| 1 | Reactivation of γ-globin expression through Cas9 or base editor to treat β-hemoglobinopathies显示文摘Dear Editor,Mutations in the β-globin gene,the essential component of adult hemoglobin(HbA;a2p2),results in either a production of aberrant sickle hemoglobin(HbS)leading to sickle cell disease(SCD)or an insufficient β-globin synthesis leading to β-thalassemia.These two major forms of β-hemoglobinopathies cause impaired erythropoiesis and life-threatening anemia.Clinical evidence has suggested that reaaivation of fetal γ-globin(HBG)gene expression which is normally silenced after birth by certain genetic mutations can ameliorate the clinical course of β-hemoglobinopathies. | Liren Wang Linxi Li Yanlin Ma Handan Hu Qi Li Yang Yang Wenbang Liu Shuming Yin Wei Li Bin Fu Ryo Kurita Yukio Nakamura Mingyao Liu Yongrong Lai Dali Li | 2020 | Cell Research2020，30，3： | 14 |
| 2 | Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants显示文摘 | Lei Yang Xiaohui Zhang Liren Wang Shuming Yin Biyun Zhu Ling Xie Qiuhui Duan Huiqiong Hu Rui Zheng Yu Wei Liangyue Peng Honghui Han Jiqin Zhang Wenjuan Qiu Hongquan Geng Stefan Siwko Xueli Zhang Mingyao Liu Dali Li | 2018 | Protein & Cell2018，9，9： | 13 |
| 3 | An Arabidopsis ctpA homologue is involved in the repair of photosystem II under high light显示文摘A T-DNA insertion mutant AtctpA1 was identified to study the physiological roles of a carboxyl-terminal processing protease (CtpA) homologue in Arabidopsis. Under normal growth conditions, disruption of AtctpA1 did not result in any apparent alterations in growth rate and thylakoid membrane protein components. However the mutant plants exhibited increased sensitivity to high irradiance. Degradation of PSII reaction center protein D1 was accelerated in the mutant during photoinhibition. These results demostrated that AtctpA1 was required for efficient repair of PSII in Arabidopsis under high irradiance. | YIN ShuMing SUN XuWu ZHANG LiXin | 2008 | Chinese Science Bulletin2008，53，7： | 6 |
| 4 | Tensile and Isothermal Fatigue Behaviors of Mg-12Gd-3Y-0.5Zr Alloy at High Temperature显示文摘Tensile and isothermal fatigue tests were carried out on an as-rolled Mg-12Gd-3Y-0.5Zr alloy and its heat-treated counterpart at different temperatures. The experimental results show that the ultimate tensile strengths of two alloys decrease very slowly with increasing temperature up to 200?C. The ultimate tensile strength of heat-treated Mg-12Gd-3Y-0.5Zr is slight lower than that of as-rolled counterpart; however, the fatigue strength of heat-treated alloy is higher. The mechanism of fatigue failure was investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It shows that cyclic slip combined with environmental effect may be the main crack initiation mechanism. | Xiaoming Yang Huajie Yang Fan Yang Shuming Yin Wei Wang Shouxin Li Qudong Wang | 2009 | Journal of Materials Science & Technology2009，25，6： | 2 |
| 5 | Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite显示文摘Tyrosine-decahydrofluorene derivatives feature a fused[6.5.6]tricarbocyclic core and a 13-membered para-cyclophane ether.Herein,we identified new xenoacremones A,B,and C(1-3)from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans.The hybrid polyketide synthaseenonribosomal peptide synthetase(PKS-NRPS)XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton.This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety.XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system.Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether,which underwent subsequent spontaneous Diels-Alder reaction to give the end products.Thus,the results indicated that three novel enzymes XenF,XenD,and XenC coordinate to assemble the[6.5.6]tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives. | Zhiguo Liu Wei Li Peng Zhang Jie Fan Fangbo Zhang Caixia Wang Shuming Li Yi Sun Shilin Chen Wenbing Yin | 2021 | Acta Pharmaceutica Sinica B2021，11，11： | 1 |
| 6 | A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing显示文摘Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease. | Xianyang Liu Jiayu Meng Xingyun Liao Yusen Liu Qian Zhou Zongren Xu Shuming Yin Qingfeng Cao Guannan Su Siyuan He Wanqian Li Xiaotang Wang Guoqing Wang Dali Li Peizeng Yang Shengping Hou | 2023 | Cellular & Molecular Immunology2023，20，11： | 0 |
| 7 | Correction to: Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants显示文摘This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://gffzzeb6f7f563f66445dhoxkob05cwkw66qwo.ffgz.tsg.suse.edu.cn/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. | Lei Yang Xiaohui Zhang Liren Wang Shuming Yin Biyun Zhu Ling Xie Qiuhui Duan Huiqiong Hu Rui Zheng Yu Wei Liangyue Peng Honghui Han Jiqin Zhang Wenjuan Qiu Hongquan Geng Stefan Siwko Xueli Zhang Mingyao Liu Dali Li | 2019 | Protein & Cell2019，10，9： | 0 |
| 8 | Genome assembly of wild loquat (Eriobotrya japonica) and resequencing provide new insights into the genomic evolution and fruit domestication in loquat显示文摘Wild loquats(Eriobotrya japonica Lindl.)provide remarkable genetic resources for studying domestication and breeding improved varieties.Herein,we generate the first high-quality chromosome-level genome assembly of wild loquat,with 45791 predicted proteincoding genes.Analysis of comparative genomics indicated that loquat shares a common ancestor with apple and pear,and a recent whole-genome duplication event occurred in loquat prior to its divergence.Genome resequencing showed that the loquat germplasms can be distinctly classified into wild and cultivated groups,and the commercial cultivars have experienced allelic admixture.Compared with cultivated loquats,the wild loquat genome showed very few selected genomic regions and had higher levels of genetic diversity.However,whole-genome scans of selective sweeps were mainly related to fruit quality,size,and f lesh color during the domestication process.Large-scale transcriptome and metabolome analyses were further performed to identify differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)in wild and cultivated loquats at various fruit development stages.Unlike those in wild loquat,the key DEGs and DAMs involved in carbohydrate metabolism,plant hormone signal transduction,f lavonoid biosynthesis,and carotenoid biosynthesis were significantly regulated in cultivated loquats during fruit development.These high-quality reference genome,resequencing,and large-scale transcriptome/metabolome data provide valuable resources for elucidating fruit domestication and molecular breeding in loquat. | Danlong Jing Xinya Liu Qiao He Jiangbo Dang Ruoqian Hu Yan Xia Di Wu Shuming Wang Yin Zhang Qingqing Xia Chi Zhang Yuanhui Yu Qigao Guo Guolu Liang | 2023 | Horticulture Research2023，10，2： | 0 |
| 9 | Long-term correction of hemophilia B through CRISPR/Cas9 induced homology-independent targeted integration显示文摘CRISPR/Cas9-mediated site-specific insertion of exogenous genes holds potential for clinical applications.However,it is still infeasible because homologous recombination(HR)is inefficient,especially for nondividing cells.To overcome the challenge,we report that a homology-independent targeted integration(HITI)strategy is used for permanent integration of high-specificity-activity Factor IX variant(F9 Padua,R338L)at the albumin(Alb)locus in a novel hemophilia B(HB)rat model.The knock-in efficiency reaches 3.66%,as determined by droplet digital PCR(dd PCR).The clotting time is reduced to a normal level four weeks after treatment,and the circulating factor IX(FIX)level is gradually increased up to 52%of the normal level over nine months even after partial hepatectomy,demonstrating the amelioration of hemophilia.Through primer-extension-mediated sequencing(PEM-seq),no significant off-target effect is detected.This study not only provides a novel model for HB but also identifies a promising therapeutic approach for rare inherited diseases. | Xi Chen Xuran Niu Yang Liu Rui Zheng Lei Yang Jian Lu Shuming Yin Yu Wei Jiahao Pan Ahmed Sayed Xueyun Ma Meizhen Liu Fengxiang Jing Mingyao Liu Jiazhi Hu Liren Wang Dali Li | 2022 | Journal of Genetics and Genomics2022，49，12： | 0 |
| 10 | Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor显示文摘Genome editing through adeno-associated viral(AAV) vectors is a promising gene therapy strategy for various diseases,especially genetic disorders. However, homologous recombination(HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivo gene therapy. Firstly, a mouse phenylketonuria(PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase(Pah) was generated. Through co-delivery of the general AAV receptor(AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitro and in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in Pah;mice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb Pah cDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of Pah cDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivo genome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy. | Shuming Yin Lie Ma Tingting Shao Mei Zhang Yuting Guan Liren Wang Yaqiang Hu Xi Chen Honghui Han Nan Shen Wenjuan Qiu Hongquan Geng Yongguo Yu Shichang Li Weishi Yu Mingyao Liu Dali Li | 2022 | Science China(Life Sciences)2022，65，4： | 0 |
| 11 | Process Optimization of Extraction Technique of Polysaccharide from Leaves of Dendrobium officinale显示文摘[Objectives] To optimize the extraction process of polysaccharides from leaves of Dendrobium officinale. [Methods]The polysaccharides from D. officinale were extracted by internal boiling method. The extraction rate of polysaccharides from D. officinale was studied.Based on the single factor experiment,the L_9( 3~3) orthogonal experiment was designed to optimize the extraction process of polysaccharides from D. officinale. [Results]The optimum process for extracting polysaccharides from D. officinale by internal boiling method was as follows:1. 00 g of D. officinale powder was desorbed with 6. 0 mL of 20% ethanol for 20 min,35. 0 mL of 90℃ water was rapidly added,and the extraction time was 5 min. [Conclusions] Under this condition,the extraction rate of polysaccharides from D. officinale was 12. 31%,which was 3. 75 percentage points higher than that of traditional reflux extraction. | Yunying ZHENG Yanzhen YIN Shuming ZHONG Ruirui ZHANG | 2018 | Medicinal Plant2018，9，5： | 0 |
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