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| 1 | One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system显示文摘 | Haifeng Wan Chunjing Feng Fei Teng Shihua Yang Baoyang Hu Yuyu Niu Andy Peng Xiang Weizhen Fang Weizhi Ji Wei Li Xiaoyang Zhao Qi Zhou | 2015 | Cell Research2015，25，2： | 39 |
| 2 | TALEN-based generation of a cynomolgus monkey disease model for human microcephaly显示文摘基因在非人类的首领编辑可以为在人探索病原学和遗传上基于的神经病学的混乱的治疗学的策略导致珍贵模型。然而,仔细在人模仿病理学、行为的赤字的神经病学的混乱的一个猴子模型成功地还没被产生了。Microcephalin 1 (MCPH1 ) 在人的大脑,和智力迟钝伴随的 MCPH1 变化原因头小畸型的进化被含有。这里,我们产生了用抄写带 biallelic MCPH1 变化的一只 cynomolgus 猴子(Macaca fascicularis ) 像使活跃之物的受动器核酸酶。猴子概括了大多数在病人观察的重要临床的特征,包括在头圆周,早熟的染色体冷凝作用(PCC ) ,语料库 callosum 的发育不全和上面的手足 spasticity 的显著减小。而且,在变异的真皮的成纤维细胞的 MCPH1 的 overexpression 救了 PCC 症候群。这个猴子模型可以帮助我们阐明在人的头小畸型并且更好的致病的 MCPH1 的角色在首领大脑尺寸的进化理解这蛋白质的功能。 | Qiong Ke Weiqiang Li Xingqiang Lai Hong Chen Lihua Huang Zhuang Kang Kai Li Jie Ren Xiaofeng Lin Haiqing Zheng Weijun Huang Yunhan Ma Dongdong Xu Zheng Chen Xinming Song Xinyi Lin Min Zhuang Tao Wang Fengfeng Zhuang Jianzhong Xi Frank Fuxiang Mao Huimin Xia Bruce T Lahn Qi Zhou Shihua Yang Andy Peng Xiang | 2016 | Cell Research2016，26，9： | 13 |
| 3 | Species-dependent neuropathology in transgenic SOD' aigs显示文摘 | Huaqiang Yang Guohao Wang Haitao Sun Runzhe Shu Tao Liu Chuan-En Wang Zhaoming Liu Yu Zhao Bentian Zhao Zhen Ouyang Dongshan Yang Jiao Huang Yueling Zhou Shihua Li Xiaodan Jiang Zhicheng Xiao Xiao-Jiang Li Liangxue Lai | 2014 | Cell Research2014，24，4： | 13 |
| 4 | Nonlinear Dynamic Analysis of Coupled Gear-Rotor-Bearing System with the Effect of Internal and External Excitations显示文摘Extensive studies on nonlinear dynamics of gear systems with internal excitation or external excitation respectively have been carried out. However, the nonlinear characteristics of gear systems under combined internal and external excitations are scarcely investigated. An eight-degree-of-freedom(8-DOF) nonlinear spur gear-rotor-bearing model, which contains backlash, transmission error, eccentricity, gravity and input/output torque, is established, and the coupled lateral-torsional vibration characteristics are studied. Based on the equations of motion, the coupled spur gear-rotor-bearing system(SGRBS) is investigated using the Runge-Kutta numerical method, and the effects of rotational speed, error fluctuation and load fluctuation on the dynamic responses are explored. The results show that a diverse range of nonlinear dynamic characteristics such as periodic motion, quasi-periodic motion, chaotic behaviors and impacts exhibited in the system are strongly attributed to the interaction between internal and external excitations. Significantly, the changing rotational speed could effectively control the vibration of the system. Vibration level increases with the increasing error fluctuation. Whereas the load fluctuation has an influence on the nonlinear dynamic characteristics and the increasing excitation force amplitude makes the vibration amplitude increase, the chaotic motion may be restricted. The proposed model and numerical results can be used for diagnosis of faults and vibration control of practical SGRBS. | ZHOU Shihua SONG Guiqiu REN Zhaohui WEN Bangchun | 2016 | Chinese Journal of Mechanical Engineering2016，29，2： | 11 |
| 5 | Dynamic Characteristics of Multi-degrees of Freedom System Rotor-bearing System with Coupling Faults of Rub-impact and Crack显示文摘Extensive studies on rotor systems with single or coupled multiple faults have been carried out. However these studies are limited to single-span rotor systems. A finite element model for a complex rotor-bearing system with coupled faults is presented. The dynamic responses of the rotor-bearing system are obtained by using the rotor dynamics theory and the modern nonlinear dynamics theory in connection with the continuation-shooting algorithm(commonly used for obtaining a periodic solution for a nonlinear system) for a range of rub-impact clearances and crack depths. The stability and Hopf instability of the periodic motion of the rotor-bearing system with coupled faults are analyzed by using the procedure described. The results indicate that the finite element method is an effective way for determining the dynamic responses of such complex rotor-bearing systems. Further for a rotor system with rub-impact and crack faults, the influences of the clearances are significantly different for different rub-impact stiffness. On the contrary, the influence of crack depths is rather small. The instability speeds of the rotor-bearing system increase due to the presence of the crack fault. The results obtained using the new finite element model, presented for computation and analysis of dynamic responses of the rotor-bearing systems with coupled faults, are in accordance with measurements in experiment. The formulations given can be used for diagnosis of faults, vibration control, and safe and stable operations of real rotor-bearing systems. | REN Zhaohui ZHOU Shihua LI Chaofeng WEN Bangchun | 2014 | Chinese Journal of Mechanical Engineering2014，27，4： | 7 |
| 6 | Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms显示文摘The infusion of coronavirus disease 2019(COVID-19)patients with mesenchymal stem cells(MSCs)potentially improves clinical symptoms,but the underlying mechanism remains unclear.We conducted a randomized,single-blind,placebo-controlled(29 patients/group)phase II clinical trial to validate previous findings and explore the potential mechanisms.Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay(P=0.0198)and less time required for symptoms remission(P=0.0194)than those who received placebo.Based on chest images,both severe and critical patients treated with MSCs showed improvement by day 7(P=0.0099)and day 21(P=0.0084).MSC-treated patients had fewer adverse events.MSC infusion reduced the levels of C-reactive protein,proinflammatory cytokines,and neutrophil extracellular traps(NETs)and promoted the maintenance of SARS-CoV-2-specific antibodies.To explore how MSCs modulate the immune system,we employed single-cell RNA sequencing analysis on peripheral blood.Our analysis identified a novel subpopulation of VNN2+hematopoietic stem/progenitorlike(HSPC-like)cells expressing CSF3R and PTPRE that were mobilized following MSC infusion.Genes encoding chemotaxis factors—CX3CR1 and L-selectin—were upregulated in various immune cells.MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro.In addition,an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling.Together,our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis. | Rongjia Zhu Tingdong Yan Yingmei Feng Yan Liu Hongcui Cao Gongxin Peng Yanlei Yang Zhen Xu Jingqi Liu Wei Hou Xiaoyue Wang Zhe Li Luchan Deng Shihua Wang Jing Li Qin Han Hongling Li Guangliang Shan Yinghao Cao Xingyan An Jianshe Yan Zhonghui Zhang Huafei Li Xuebin Qu Jiaqi Zhu Shumin Zhou Jiao Wang Fengchun Zhang Jinming Gao Ronghua Jin Dayong Xu Yan-Qing Ma Tao Huang Shuang Peng Zhi Zheng Ilia Stambler Eric Gilson Lee Wei Lim Alexey Moskalev Antonio Cano Sasanka Chakrabarti Brun Ulfhake Huanxing Su Haoying Xu Sihuan Xu Feng Wei Holly MBrown-Borg Kyung-Jin Min Georgina Ellison-Hughes Calogero Caruso Kunlin Jin Robert Chunhua Zhao | 2021 | Cell Research2021，31，12： | 5 |
| 7 | Simulations and Experimental Investigation on Motion Stability of a Flexible Rotor-bearing System with a Transverse Crack显示文摘In the classical process for stability studies on the rotor-bearing system with crack faults,the simple discrete model is adopted for research on such problems,which neglect some needful dynamical influence factor,such as the material damping,shearing effect and gyroscopic effects,etc.Therefore,it is necessary to find a precise calculation model for simulation of the rotor-bearing system with cracks faults.In this paper,instead of the traditional simple discrete model,finite element(FE)model is adopted to investigate the motion stability of a nonlinear rotor system with crack fault.According to finite element theory,the FE model of the cracked rotor system is established firstly.It should be pointed out that the element where the crack occurs is modeled by a particular crack element and the supports at both ends are simulated by two nonlinear loads.Then,based on dimensionless and dimensionality reduction,the Newmark-βmethod and the shooting method are employed to study the effect of eccentricity and the depth of crack on instability speed and bifurcation feature.Furthermore,the simulation results are verified by some corresponding experiments.The simulation and experimental results show that instability speed does not change monotonically,but decreases firstly and then increases when the amount of eccentricity increases.Moreover,as the type of instability changes,the instability speed jumps concomitantly.Additionally,the presence of crack fault can disturb the oil whirl,as a result,instability speed tends to increase slightly,but it does not affect the type of instability and jumping phenomenon.This research presents an effective and convenient method which uses the finite element method(FEM)to research the motion stability of the nonlinear rotor-bearing system with cracked faults and other nonlinear force,and the proposed method can provide a theoretical reference for stability analysis and vibration control in more complex relevant rotor-bearing system. | LI Chaofeng YU Hexing ZHOU Shihua WEN Bangchun | 2013 | Chinese Journal of Mechanical Engineering2013，26，6： | 5 |
| 8 | HBB-deficient Macaca fascicularis monkey presents with human β-thalassemia显示文摘Dear Editor,β-Thalassemia is a common severe genetic disease caused by mutations in HBB and affects approximately 1.5% of the global population (Origa, 2017). In southern China, the carrier rate of β-thalassemia is as high as 6.43%, creating a high socio-economic burden (Xiong et al., 2010). In adult humans, there are three types of hemoglobin: HbA1 (~97%), HbA2 (~2%) and HbF (~1%). HbA1 (α2β2) is composed of two a-globin and two β-globi n sub units en coded by HBA and HBB, respectively;HbF (α2β2)is made up of two α-globin subunits and two β-globin sub units en coded by HBG. Mutations in the coding region or regulatory region of HBB are involved in β-thalassemia pathogenesis. Except for some rare dominant mutations, most HBB mutations are recessive (Origa, 2017). Depending on the mutation type, the β-globin level will either be reduced or completely depleted, resulting in α-globin accumulation and precipitation. These α-globin precipitates lead to red blood cell death, resulting in anemia and tissue damage, and even death in thalassemia major patients. Blood transfusions can help slow disease progression but lead to iron overload, ultimately resulting in iron toxicity. Bone marrow transfer is the only cure in the clinic and is available only to a small percentage of patients with human leukocyte antigervmatched donors. Recently, gene therapy and gene editing therapy have shown great promise in curing β-thalassemia (Glaser et al., 2015;Thompson et al., 2018). However, no appropriate animal models are available for evaluating the safety and efficacy of such advanced therapeutic strategies in vivo.β-thalassemia mice are the sole animal model available for research. However, substantial differences have been reported between the types and expressi on patter ns of human and mouse globins (McColl and Vadolas, 2016). Moreover, mice contain no fetal globin gene equivalent, and homozygous mutations of HBB in mouse for early models of β-thalassemia major or Cooley anemia are all embryonic lethal (Huo et al., 2009). Recently, significant phenotype and physiology differences have been reported between SIRT6- null mice and the non-human primate model (Zhang et al., 2018). Thus, an appropriate non-human primate model is needed for human β-thalassemia studies and treatments. | Yan Huang Chenhui Ding Puping Liang Duanduan Li Yu Tang Wei Meng Hongwei Sun Hongyu Lu Yu Chen Xueying Chen Qunshan Huang Jianpei Fang Canquan Zhou Shihua Yang Junjiu Huang | 2019 | Protein & Cell2019，10，7： | 4 |
| 9 | Design and Implementation of Terminal Sliding Mode Control Method for PMSM Speed Regulation System 显示文摘 | Shihua Li Mingming Zhou Xinghuo Yu | 2013 | IEEE TRANSACTIONS ON INDUSTRIAL INFORMATICS2013，9，4： | 1 |
| 10 | Dynamic Characteristics of Lubrication and Wear Prediction of Slipper/Swash-Plate in Axial Piston Pumps显示文摘A novel dynamic model describing the slipper posture of the swash plate in axial piston pumps is proposed, taking into account the hydrodynamic and squeezing effects, which involves three degrees of freedom. The variation in the lubricating film thickness and the slipper tilt are accurately calculated. The influence of hydrodynamic effects and charging pressure on the slipper lubrication is discussed. The minimum film thickness, the overturning angle and the azimuth angle are obtained.Then, the trajectory of minimum thickness on the friction surface of the swash plate is predicted, the accuracy of which can be verified with the abrasion distribution of an actual swash plate. Research results can predict the durability and provide theoretical help for the design of the slipper. | Jichen Zhou Junjie Zhou Chongbo Jing Shihua Yuan Anlin Luo | 2019 | Journal of Beijing Institute of Technology2019，28，3： | 1 |
| 11 | Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry显示文摘The outbreak of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2 has created a global health crisis. SARS-CoV-2 infects varieties of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative viral entry pathways. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. Beyond known host proteins, i.e., ACE2, TMPRSS2, and NRP1, we identified multiple host components,among which LDLRAD3, TMEM30A, and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike’s N-terminal domain(NTD). Their essential and physiological roles have been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in an ACE2-independent fashion. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of COVID-19 countermeasures. | Shiyou Zhu Ying Liu Zhuo Zhou Zhiying Zhang Xia Xiao Zhiheng Liu Ang Chen Xiaojing Dong Feng Tian Shihua Chen Yiyuan Xu Chunhui Wang Qiheng Li Xuran Niu Qian Pan Shuo Du Junyu Xiao Jianwei Wang Wensheng Wei | 2022 | Science China(Life Sciences)2022，65，4： | 1 |
| 12 | Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor显示文摘 | Lu Yang Xiaozhuo Liu Zengbing Lu Judy Yuet-Wa Chan LinLi Zhou Kwok-Pui Fung Ping Wu Shihua Wu | 2010 | Cancer Letters2010，，1： | 1 |
| 13 | Dis- turbance Observer Based Terminal Sliding Mode Control Method for Pmsm Speed Regulation System 显示文摘 | LI Shihua ZHOU Mingming YU Xinghuo | 2011 | Proceedings of the 30th Chinese Control Con- ference July 22-242011，，： | 1 |
| 14 | Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor显示文摘 | Lu Yang Xiaozhuo Liu Zengbing Lu Judy Yuet-Wa Chan LinLi Zhou Kwok-Pui Fung Ping Wu Shihua Wu | 2010 | Cancer Letters2010，，1： | 1 |
| 15 | Disturbance rejection control method for permanent magnet synchronous motor speed-regulation system显示文摘 | Li Shihua Xia Cunjian Zhou Xuan | 2012 | Mechatronics2012，22，6： | 1 |
| 16 | Vibration isolation performance analysis of a bilateral supported bio-inspired anti-vibration control system显示文摘To achieve better anti-vibration performance in a low frequency region and expand the range of vibration isolation,a bilateral supported bio-inspired anti-vibration(BBAV)structure composed of purely linear elements is proposed,inspired by the motion form of bird legs and the nonlinear extension and compression of muscles and tendons.The kinematic relations and nonlinear dynamic model considering vertical and rotational vibrations are established.The loading capacity and equivalent stiffness are investigated with key parameters.The amplitude-frequency characteristics and force transmissibility are used to evaluate the stability and anti-vibration performance with the effects of the excitation amplitude,rod length,installation angle,and spring stiffness.The results show that the loading requirements and resonant characteristics of the BBAV structure are adjustable,and superior vibration isolation performance can be achieved readily by tuning the parameters.The X-shaped vibration structure is sensitive to the spring stiffness,which exhibits a wider vibration isolation bandwidth with smaller spring stiffness.Besides,depending on the parameters,the nonlinear behavior of the BBAV system can be interconverted between the softening type and the hardening type.The theoretical analysis in this study demonstrates the advantages and effectiveness of the vibration isolation structure. | Shihua ZHOU Dongsheng ZHANG Bowen HOU Zhaohui REN | 2023 | Applied Mathematics and Mechanics(English Edition)2023，44，5： | 0 |
| 17 | A single-nucleus transcriptomic atlas of the dog hippocampus reveals the potential relationship between specific cell types and domestication显示文摘The process of domestication has led to dramatic differences in behavioral traits between domestic dogs and gray wolves.Whole-genome research found that a class of putative positively selected genes were related to various aspects of learning and memory,such as long-term potentiation and long-term depression.In this study,we constructed a single-nucleus transcriptomic atlas of the dog hippocampus to illustrate its cell types,cell lineage and molecular features.Using the transcriptomes of 105057 nuclei from the hippocampus of a Beagle dog,we identified 26 cell clusters and a putative trajectory of oligodendrocyte development.Comparative analysis revealed a significant convergence between dog differentially expressed genes(DEGs)and putative positively selected genes(PSGs).Forty putative PSGs were DEGs in glutamatergic neurons,especially in Cluster 14,which is related to the regulation of nervous system development.In summary,this study provides a blueprint to understand the cellular mechanism of dog domestication. | Qi-Jun Zhou Xingyan Liu Longlong Zhang Rong Wang Tingting Yin Xiaolu Li Guimei Li Yuqi He Zhaoli Ding Pengcheng Ma Shi-Zhi Wang Bingyu Mao Shihua Zhang Guo-Dong Wang | 2022 | National Science Review2022，9，11： | 0 |
| 18 | The influence of fractionation of REE-enriched minerals on the zircon partition coefficients显示文摘Zircon is widely used to simulate melt generation,migration and evolution within the crust and mantle.The achievable performance of melt modelling generally depends on the availability of reliable trace element partition coefficients(D).However,a large range of D_(REE) values for zircon from natural samples and experimental studies has been reported,with values spanning up to 3 orders of magnitude.Unfortunately,a gap of knowledge on this variability is evident.In this study we model the crystallization processes of common REE-bearing minerals from granitic melts and show that the measured zircon D_(REE) would be elevated if there is crystallization of REE-enriched minerals subsequent to zircon.Nevertheless,compared to zircon D_(REE) values measured from experimental studies,this mechanism appears to have a less significant influence on those from natural granite samples since the quantity of crystallized REE-enriched minerals is very low in natural magmatic systems and/or most of them crystallize prior to zircon.Combined with recently published studies,this work supports that analysis of natural zircon/host groundmass pairs provides more robust D_(REE) values applicable to natural systems than those measured from experimental studies,which can be used to constrain the provenance of detrital zircons. | Shihua Zhong Sanzhong Li Reimar Seltmann Zhiqing Lai Jie Zhou | 2021 | Geoscience Frontiers2021，12，3： | 0 |
| 19 | A neutralizing-protective supersite of human monoclonal antibodies for yellow fever virus显示文摘The yellow fever virus(YFV)is a life-threatening human pathogen.Owing to the lack of available therapeutics,non-vaccinated individuals are at risk.Here,we isolated eight human monoclonal antibodies that neutralize YFV infection.Five recognized overlapping epitopes and exhibited potent neutralizing activity.Two(YD6 and YD73)were ultra-potent and conferred complete protection against the lethal challenge of YFV as both prophylactics and therapeutics in a mouse model.Crystal structures revealed that YD6 engaged the YFV envelope protein in both pre-and post-fusion states,suggesting viral inhibition by a“double-lock”mechanism.The recognition determinants for YD6 and YD73 are clustered at the premembrane(prM)-binding site.Notably,antibodies targeting this site were present in minute traces in YFV-infected individuals but contributed significantly to neutralization,suggesting a vulnerable supersite of YFV.We provide two promising candidates for immunotherapy against YFV,and the supersite represents an ideal target for epitope-based vaccine design. | Yan Li Zhihai Chen Lili Wu Lianpan Dai Jianxun Qi Yan Chai Shihua Li Qihui Wang Zhou Tong Sufang Ma Xiaomin Duan Shuning Ren Rui Song Mifang Liang Wenjun Liu Jinghua Yan George F.Gao | 2022 | The Innovation2022，3，6： | 0 |
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