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Tensile and Isothermal Fatigue Behaviors of Mg-12Gd-3Y-0.5Zr Alloy at High Temperature

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Journal of Materials Science & Technology 2009年第6期25卷 731-737页

作者： Xiaoming Yang Huajie Yang Fan Yang shuming yin Wei Wang Shouxin Li Qudong Wang Shenyang National Laboratory for Materials Science Institute of Metal Research Chinese Academy of Sciences Shenyang 110016 China National Engineering Research Center of Light Alloys Net Forming Shanghai Jiao Tong University Shanghai 200020 China

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℃. 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.

关键词： Mg-12Gd-3Y-0.5Zr Isothermal fatigue Fatigue strength Tensile strength

Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats

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Science China(Life Sciences) 2024年第12期67卷 2575-2586页

作者： Dexin Zhang Rui Zheng Zhoutong Chen Liren Wang Xi Chen Lei Yang Yanan Huo shuming yin Dan Zhang Jiaxin Huang Xingang Cui Dali Li Hongquan Geng Department of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Urology Children’s Hospital of Fudan UniversityShanghai 201100China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China

Primary hyperoxaluria type 1(PH1)is a severe hereditary disease,leading to the accumulation of oxalate in multiple organs,particularly the *** oxidase 1(HAO1),a pivotal gene involved in oxalate production,is an approved target for the treatment of *** this study,we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1c.290-2 A in vivo with lipid nanoparticles(LNP)delivered adenine base editing(ABE)mRNA.A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver,leading to the sustainable normalization of urinary oxalate(for at least 6 months)and complete rescue of the pathophysiology in PH1 ***,a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over 60%Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 *** findings suggest that the LNP-mediated base-editing of Hao1c.290-2 A is an efficient and safe approach to PH1 therapy,highlighting its potential utility in clinical settings.

关键词： primary hyperoxaluria type 1 lipid nanoparticles hydroxyacid oxidase 1 base editing

Long-term correction of hemophilia B through CRISPR/Cas9 induced homology-independent targeted integration

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Journal of Genetics and Genomics 2022年第12期49卷 1114-1126页

作者： 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 Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China The MOE Key Laboratory of Cell Proliferation and Differentiation Genome Editing Research CenterSchool of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Xinhua Hospital Shanghai Jiao Tong University School of MedicineShanghai 200092China Biochemistry Laboratory Chemistry DepartmentFaculty of ScienceAssiut UniversityAssiut 71516Egypt Shanghai Turtle Technology Co. Shanghai 201900China

CRISPR/Cas9-mediated site-specific insertion of exogenous genes holds potential for clinical ***,it is still infeasible because homologous recombination(HR)is inefficient,especially for nondividing *** 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 *** 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 *** primer-extension-mediated sequencing(PEM-seq),no significant off-target effect is *** study not only provides a novel model for HB but also identifies a promising therapeutic approach for rare inherited diseases.

关键词： Hemophilia B Alb FIX CRISPR/Cas9-mediated HITI Gene therapy

A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

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Cellular & Molecular Immunology 2023年第11期20卷 1379-1392页

作者： 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 The First Affiliated Hospital of Chongqing Medical University ChongqingChina Chongqing Key Laboratory of Ophthalmology ChongqingChina Chongqing Eye Institute ChongqingChina Sichuan Provincial Key Laboratory for Human Disease Gene Study Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu611731China Department of Medical Oncology Chongqing University Cancer HospitalChongqing400030China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai200241China Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Sciences Key LaboratoryBeijing100730China

Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged ***,the etiology of VKH disease remains ***,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)*** MPP2-N315 mutation was highly deleterious according to bioinformatic ***,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 *** 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 *** 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 ***,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 ***,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.

关键词： Vogt-Koyanagi-Harada disease Whole exome sequencing De novo mutation Membrane palmitoylated protein 2 Annexin A2 ERK3/IL-17E pathway

Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor

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Science China(Life Sciences) 2022年第4期65卷 718-730页

作者： 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 Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai200241China Bioray Laboratories Inc. Shanghai200241China Xinhua Hospital Shanghai Jiao Tong University School of MedicineShanghai200092China College of Physical Education and Health East China Normal UniversityShanghai200241China Key Laboratory of Adolescent Health Assessment and Exercise Intervention Ministry of EducationCollege of Physical Education and HealthEast China Normal UniversityShanghai200241China CIPHER GENE LLC Beijing100089China

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.

关键词： CRISPR/Cas9 gene therapy adeno-associated virus(AAV) AAVR Pah PKU

Theoretical and experimental study on high-entropy flotation of micro-fine cassiterite

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International Journal of Mining Science and Technology 2025年第1期35卷 19-39页

作者： shuming Wen Yongchao Miao Yanyu Tang Zhengyong Song Qicheng Feng State Key Laboratory of Complex Nonferrous Metal Resources Clean Utilization Faculty of Land Resource EngineeringKunming University of Science and TechnologyKunming 650093China

Tin is a critical metal for various industries,making its recovery from low-grade cassiterite ores *** study aimed to optimize the flotation recovery of cassiterite using multi-component collector *** collectors were initially selected through micro-flotation tests,leading to the identification of optimal proportions for a four-component collector system(SHA-OHA-SPA-DBIA in a 4:3:2:1 ratio).Molecular dynamics simulations and surface tension tests were used to investigate the micellar behavior of these collectors in aqueous *** adsorption characteristics were quantified using microcalorimetry,enabling the determination of collection entropy and changes in Gibbs free *** four-component collector system showed the highest entropy change and the most favorable Gibbs free energy,leading to a cassiterite recovery of above 90%at a concentration of 8.0×10^(5)mol/*** analytical techniques were employed to systematically characterize the adsorption *** findings revealed a positive correlation between the adsorption products formed by the multicomponent collectors on the cassiterite surface and the entropy ***-scale testing of the high-entropy collector system produced a tin concentrate with an Sn grade of 6.17%and an Sn recovery of 82.43%,demonstrating its substantial potential for practical applications in cassiterite flotation.

关键词： High-entropy Flotation Cassiterite Adsorption Molecular dynamics QCM-D

Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants

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Protein & Cell 2018年第9期9卷 814-819页

作者： 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 East China Normal University and Shanghai Fengxian DistrictCentral Hospital Joint Center for Translational Medicine ShanghaiKey Laboratory of Regulatory Biology School of Life SciencesEast China Normal University Shanghai 200241 China Fengxian Hospital Affiliated to Southern Medical University Shanghai 201499 China Xinhua Hospital Shanghai Jiao Tong University School ofMedicine Shanghai 200092 China School of Life Sciences Hunan Normal University Changsha 410081 China Bioray Laboratories Inc. Shanghai 200241 China Department of Molecular and Cellular Medicine The Institute of Biosciences and Technology Texas AM University Health Science Center Houston TX 77030 USA

Dear Editor, The clustered regularly interspaced short palindromic repeat （CRISPR） system has been widely adapted to genome editing to either introduce or correct genetic mutations （Wang et al., 2016）. However, due to competition with the dominant non-homologous end-joining （NHEJ） pathway, precise genome modifications through Cas9-stimulated homologous recombination （HR） is inefficient. Through fusion of cytidine deaminases, APOBEC1 （apolipoprotein B editing complex 1） or AID （activation-induced deaminase）, with Cas9 variants, several groups have developed the cytidine base editor （BE） systems （Komor et al., 2016; Li et al., 2018; Nishida et al., 2016）. The BE system achieves programmable conversion of C-G base pairs to T.A without double-stranded DNA cleavage （Zhou et al., 2017）. More recently, adenine base editors （ABEs）, which efficiently convert A-T base pairs to G-C in genomic DNA, have been developed via fusion of an engineered tRNA adenosine deaminase （ecTadA from Escherichia coh） with nCas9 （Gaudelli et al., 2017）. The ABE system has quickly been adapted to generate disease models and correction of genetic disease in mice （Ryu et al., 2017; Liu et al, 2018）. However, whether the editing efficiency and the targeting scope of ABE could be improved is largely unexplored. In this study, we describe the efficient generation of base-edi- ted mice and rats modeling human diseases through ABEs with highest efficiency up to 100%. We also demonstrate an increase of ABE activity through injection of chemically modified tracrRNA and crRNA in mouse zygotes, and the expansion of editing scope by fusion of an ecTadA mutant to SaCas9n-KKH and Casgn-VQR variants in both cells and embryos. Our study suggests that the ABE system is a powerful and convenient tool to introduce precise base conversions in rodents.

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一种卫星相控阵天线在轨校正方法

无线电工程 2022年第11期52卷 2035-2040页

作者：单长胜尹曙明王烁黄蕾北京空间信息传输中心北京102300 华东电子工程研究所安徽合肥230088

为提升波束合成性能,提出了一种新的卫星相控阵天线(Phase Array Antenna,PAA)在轨校正方法,即多通道特性检测及补偿(Multi-channel Detection and Calibration,MUDEC)方法。MUDEC先通过通道间相关检测,完成对多路信号传输时延、幅度和... 详细信息

为提升波束合成性能,提出了一种新的卫星相控阵天线(Phase Array Antenna,PAA)在轨校正方法,即多通道特性检测及补偿(Multi-channel Detection and Calibration,MUDEC)方法。MUDEC先通过通道间相关检测,完成对多路信号传输时延、幅度和相位的初始补偿;再利用最小均方误差(Minimum Mean Square Error,MMSE),实现多路信号幅度、相位的加权调整,进一步增强算法的鲁棒性;还将MUDEC与旋转矢量(Rotating-element Electric-field Vector,REV)法、酉变换编码(Unitary Transform Encoding,UTE)法和环路调整编码(Control Circuit Encoding,CCE)法等进行了比较分析,从而说明MUDEC无需增加星上硬件设备,且所需处理时间与资源相对较少,更适宜在实际中应用。

关键词：相控阵天线校正多通道

静电激发袋式除尘器(ESFF)阻力数学模型分析

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环境工程学报 2017年第3期11卷 1660-1666页

作者：王宁王祖武李海玮叶寅肖述明武汉大学资源与环境科学学院武汉430072

静电激发袋式除尘器(ESFF),又称静电强化纤维过滤复合电袋除尘器,是一种新型的高效、低阻的除尘方式。基于传统的Kozeny-Carman(K-C)袋除尘阻力模型和静电强化纤维过滤理论,构建了ESFF的完整阻力模型,并利用MATLAB工具箱首次对ESFF的低... 详细信息

静电激发袋式除尘器(ESFF),又称静电强化纤维过滤复合电袋除尘器,是一种新型的高效、低阻的除尘方式。基于传统的Kozeny-Carman(K-C)袋除尘阻力模型和静电强化纤维过滤理论,构建了ESFF的完整阻力模型,并利用MATLAB工具箱首次对ESFF的低阻成因进行了精确的数学描述。为了明确ESFF与袋除尘器阻力组成的内在联系,提出了阻力修正系数PRF,并探究了不同实验参数对PRF的影响,建立了一个新的阻力性能评价指标。实验结果表明,提高放电电压和降低粉尘负荷均会导致PRF变小,系统阻力变低。

关键词：静电激发袋式除尘器(ESFF) 滤袋阻力阻力模型阻力修正系数(PRF)