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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 | A Chromosome-Scale Genome Assembly of Paper Mulberry(Bmussonetia papyrifera)Provides New Insights into Its Forage and Papermaking Usage显示文摘Paper mulberry(Broussonetia papyrifera)is a well-known woody tree historically used for Cai Lun papermaking,one of the four great inventions of ancient China.More recently,Paper mulberry has also been used as forage to address the shortage of feedstuff because of its digestible crude fiber and high protein contents.In this study,we obtained a chromosome-scale genome assembly for Paper mulberry using integrated approaches,including Illumina and PacBio sequencing platform as well as Hi-C,optical,and genetic maps.The assembled Paper mulberry genome consists of 386.83 Mb,which is close to the estimated size,and 99.25%(383.93 Mb)of the assembly was assigned to 13 pseudochromosomes.Comparative genomic analysis revealed the expansion and contraction in the flavonoid and lignin biosynthetic gene families,respectively,accounting for the enhanced flavonoid and decreased lignin biosynthesis in Paper mulberry.Moreover,the increased ratio of syringyl-lignin to guaiacyl-lignin in Paper mulberry underscores its suitability for use in medicine,forage,papermaking,and barkcloth making.We also identified the rootassociated microbiota of Paper mulberry and found that Pseudomonas and Rhizobia were enriched in its roots and may provide the source of nitrogen for its stems and leaves via symbiotic nitrogen fixation.Collectively,these results suggest that Paper mulberry might have undergone adaptive evolution and recruited nitrogen-fixing microbes to promote growth by enhancing flavonoid production and altering lignin monomer composition.Our study provides significant insights into genetic basis of the usefulness of Paper mulberry in papermaking and barkcloth making,and as forage.These insights will facilitate further domestication and selection as well as industrial utilization of Paper mulberry worldwide. | Xianjun Peng Hui Liu Peilin Chen Feng Tang Yanmin Hu Fenfen Wang Zhi Pi Meiling Zhao Naizhi Chen Hui Chen Xiaokang Zhang Xueqing Yan Min Liu Xiaojun Fu Guofeng Zhao Pu Yao Lili Wang He Dai Xuming Li Wei Xiong Wencai Xu Hongkun Zheng Haiyan Yu Shihua Shen | 2019 | Molecular Plant2019，12，5： | 18 |
| 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 | Mesenchymal stem cells and immune disorders: from basic science to clinical transition显示文摘As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e.,“subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://gffzzd3f38a9638994581hwxb66oc955ov6fun.ffgz.tsg.suse.edu.cn) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application. | Shihua Wang Rongjia Zhu Hongling Li Jing Li Qin Han Robert Chunhua Zhao | 2019 | Frontiers of Medicine2019，13，2： | 12 |
| 5 | Synthesis of Branched Chains with Actuation Redundancy for Eliminating Interior Singularities of 3T1R Parallel Mechanisms显示文摘Although it is common to eliminate the singularity of parallel mechanism by adding the branched chain with actuation redundancy, there is no theory and method for the configuration synthesis of the branched chain with actuation redundancy in parallel mechanism. Branched chains with actuation redundancy are synthesized for eliminating interior singularity of 3-translational and 1-rotational(3T1R) parallel mechanisms. Guided by the discriminance method of hybrid screw group according to Grassmann line geometry, all the possibilities are listed for the occurrence of interior singularities in 3T1R parallel mechanism. Based on the linear relevance of screw system and the principles of eliminating parallel mechanism singularity with actuation redundancy, different types of branched chains with actuation redundancy are synthesized systematically to indicate the layout and the number of the branched chainsinterior with actuation redundancy. A general method is proposed for the configuration synthesis of the branched chains with actuation redundancy of the redundant parallel mechanism, and it builds a solid foundation for the subsequent performance optimization of the redundant actuation parallel mechanism. | LI Shihua LIU Yanmin CUI Hongliu NIU Yunzhan ZHAO Yanzhi | 2016 | Chinese Journal of Mechanical Engineering2016，29，2： | 11 |
| 6 | Dissecting the Genetic Basis of Grain Shape and Chalkiness Traits in Hybrid Rice Using Multiple Collaborative Populations显示文摘 | Junyi Gong Jiashun Miao Yan Zhao Qiang Zhao Qi Feng Qilin Zhan Benyi Cheng Junhui Xia Xuehui Huang Shihua Yang Bin Han | 2017 | Molecular Plant2017，10，10： | 8 |
| 7 | Differentiation of illicit drugs with THz time-domain spectroscopy显示文摘The terahertz time-domain spectroscopy(THz-TDS) was used for sensing and identifying illicit drugs.The absorption spectra of seven illicit drug samples(morphine and its hydrochloride,cocaine hydrochloride,codeine phosphate,papaverine hydrochloride,pethidine hydrochloride,and thebaine) were studied by THz-TDS at 0.3-2.0 THz at room temperature.The geometric structure and vibration frequencies of morphine were calculated by density functional theory.The four absorption features were dominated by intra-/inter-molecular collective or lattice vibration modes.Each illicit drug has a distinct signature in its THz spectra.The results indicate that the THz-TDS can be used to identify and discriminate illicit drugs by their characteristic fingerprints. | LIU Guifeng MA Shihua JI Te ZHAO Hongwei WANG Wenfeng | 2010 | Nuclear Science and Techniques2010，21，4： | 7 |
| 8 | 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 |
| 9 | A Diagnostic Analysis on the Effect of the Residual Layer in Convective Boundary Layer Development near Mongolia Using 20th Century Reanalysis Data显示文摘Although the residual layer has already been noted in the classical diurnal cycle of the atmospheric boundary layer,its effect on the development of the convective boundary layer has not been well studied. In this study, based on 3-hourly20 th century reanalysis data, the residual layer is considered as a common layer capping the convective boundary layer. It is identified daily by investigating the development of the convective boundary layer. The region of interest is bounded by(30°–60° N, 80°–120° E), where a residual layer deeper than 2000 m has been reported using radiosondes. The lapse rate and wind shear within the residual layer are compared with the surface sensible heat flux by investigating their climatological means, interannual variations and daily variations. The lapse rate of the residual layer and the convective boundary layer depth correspond well in their seasonal variations and climatological mean patterns. On the interannual scale, the correlation coefficient between their regional averaged(40°–50°N, 90°–110° E) variations is higher than that between the surface sensible heat flux and convective boundary layer depth. On the daily scale, the correlation between the lapse rate and the convective boundary layer depth in most months is still statistically significant during 1970–2012. Therefore, we suggest that the existence of a deep neutral residual layer is crucial to the formation of a deep convective boundary layer near the Mongolian regions. | HAN Bo ZHAO Cailing L Shihua WANG Xin | 2015 | Advances in Atmospheric Sciences2015，32，6： | 5 |
| 10 | Mesenchymal stem cell-derived small extracellular vesicles mitigate oxidative stress-induced senescence in endothelial cells via regulation of miR-146a/Src显示文摘Senescent endothelial cells (ECs) could impair the integrity of the blood vessel endothelium, leading to vascular aging and a series of diseases, such as atherosclerosis, diabetes. Preventing or mitigating EC senescence might serve as a promising therapeutic paradigm for these diseases. Recent studies showed that small extracellular vesicles (sEV) have the potential to transfer bioactive molecules into recipient cells and induce phenotypic changes. Since mesenchymal stem cells (MSCs) have long been postulated as an important source cell in regenerative medicine, herein we investigated the role and mechanism of MSC-derived sEV (MSC-sEV) on EC senescence. In vitro results showed that MSC-sEV reduced senescent biomarkers, decreased senescence-associated secretory phenotype (SASP), rescued angiogenesis, migration and other dysfunctions in senescent EC induced by oxidative stress. In the In vivo natural aging and type-2 diabetes mouse wound-healing models (both of which have senescent ECs), MSC-sEV promoted wound closure and new blood vessel formation. Mechanically, miRNA microarray showed that miR-146a was highly expressed in MSC-sEV and also upregulated in EC after MSC-sEV treatment. miR-146a inhibitors abolished the stimulatory effects of MSC-sEV on senescence. Moreover, we found miR-146a could suppress Src phosphorylation and downstream targets VE-cadherin and Caveolin-1. Collectively, our data indicate that MSC-sEV mitigated endothelial cell senescence and stimulate angiogenesis through miR-146a/Src. | Xian Xiao Meiqian Xu Hongliang Yu Liping Wang Xiaoxia Li Janusz Rak Shihua Wang Robert Chunhua Zhao | 2021 | Signal Transduction and Targeted Therapy2021，6，11： | 5 |
| 11 | 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 |
| 12 | Results of Clinical Trial of Superficially-placed Tumor Therapy with Carbon Ions at Heavy Ion Research Facility in Lanzhou(HIRFL显示文摘 | Zhang Hong Li Sha Wang Xiaohu Li Qiang Zhao Weiping Dai Zhongying Wei Shihua Gao Liying Xiao Guoqing Xu Hushan Hu Zhengguo Mao Ruishi Yue Yangjun Ran Juntao Tian Zhongze Song Mingtao Zhao Hongwei Zhan Wenlong | 2007 | 近代物理研究所和兰州重离子加速器实验室年报:英文版2007，，1： | 2 |
| 13 | MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2显示文摘 | Yang Zeng Xuebin Qu Hongling Li Shan Huang Shihua Wang Qilin Xu Ruizhu Lin Qin Han Jing Li Robert Chunhua Zhao | 2012 | FEBS Letters2012，，16： | 2 |
| 14 | Diagnostic Accuracy of Three-Dimensional Whole-Heart Magnetic Resonance Angiography to Detect Coronary Artery Disease with Invasive Coronary Angiography as a Reference:A Meta-Analysis显示文摘Objective:We aimed to evaluate the diagnostic performance of three-dimensional whole-heart magnetic resonance coronary angiography(MRCA)in detecting coronary artery disease(CAD)with invasive coronary angiography as the reference standard.Methods:We searched PubMed and Embase for studies evaluating the diagnostic performance of three-dimensional whole-heart MRCA for the diagnosis of CAD with invasive coronary angiography as the reference standard.The bivariate mixed-effects regression model was applied to synthesize available data.The clinical utility of whole-heart MRCA was calculated by the posttest probability based on Bayes’s theorem.Results:Eighteen studies were included,of which 16 provided data at the artery level.Patient-based analysis revealed a pooled sensitivity of 0.90(95%confi dence interval[CI]0.87–0.93)and specifi city of 0.79(95%CI 0.73–0.84),while the pooled estimates were 0.86(95%CI 0.82–0.89)and 0.89(95%CI 0.84–0.92),respectively,at the artery level.The areas under the summary receiver operating characteristic curve were 0.93(95%CI 0.90–0.95)and 0.92(95%CI 0.90–0.94)at the patient and artery levels,respectively.With a pretest probability of 50%,the patients’posttest probabilities of CAD were 81%for positive results and 11%for negative results.Conclusions:Whole-heart MRCA can be an alternative noninvasive method for diagnosis and assessment of CAD. | Shiqin Yu Chen Cui Minjie Lu Shihua Zhao | 2020 | Cardiovascular Innovations and Applications2020，，1： | 2 |
| 15 | Correlation and Significance of Midkine and Estrogen Receptor Beta Protein Expression in Non-Small Cell Lung Cancer显示文摘OBJECTIVE Midkine (MK),a new member of the heparin-binding growth factor family,was found recently to have a highexpression level in many carcinoma specimens,including thoseof the esophagus,gall bladder,pancreas,colorectum,breast andlung.Estrogen receptor beta (ER-β),a recently cloned estrogenreceptor subtype,was also found to be highly expressed in lungtumor tissue,in contrast to a lower level of expression in normallung tissue.However,few relevant studies on these proteins havebeen published.The aims of our study were to investigate theexpression of midkine and ER-β proteins in non-small cell lungcancer (NSCLC) and to examine the relationship between theirexpression and the clinicopathologic data as well as to analyse thecorrelation of their expression in NSCLC.METHODS By immunohistochemistry,MK and ER-β were ex-amined in 24 surgically resected cases of NSCLC with their corre-sponding paraneoplastic and normal lung tissues.RESULTS MK and ER-β were overexpressed in NSCLC.Thelevels of MK and ER-β expression in NSCLC were found to be sig-nificantly negatively correlated with the pathological classification(P=0.042 and 0.021,respectively),and their expression decreasedwith a raise in the classification.Spearman's correlation analysisshowed that the correlation of their expression in NSCLC wasstrong (correlation coefficient[r_s]= 0.535,P=0.007<0.01).CONCLUSION The expression levels of MK and ER-β to someextent reflect the malignant degree of NSCLC,and their combineddetection may be of great value in early diagnosis,treatments ofpatients with NSCLC and can predict the prognoses. | Shihua Zhang Guangfeng Zhao Qingling Wang Kaihua Lu Yayi Hou | 2008 | Chinese Journal of Clinical Oncology2008，5，6： | 2 |
| 16 | Nanobody-based chimeric antigen receptor T cells designed by CRISPR/Cas9 technology for solid tumor immunotherapy显示文摘Chimeric antigen receptor-based T-cell immunotherapy is a promising strategy for treatment of hematological malignant tumors;however,its efficacy towards solid cancer remains challenging.We therefore focused on developing nanobody-based CAR-T cells that treat the solid tumor.CD105 expression is upregulated on neoangiogenic endothelial and cancer cells.CD105 has been developed as a drug target.Here we show the generation of a CD105-specific nanobody,an anti-human CD105 CAR-T cells,by inserting the sequences for anti-CD105 nanobody-linked standard cassette genes into AAVS1 site using CRISPR/Cas9 technology.Co-culture with CD105+target cells led to the activation of anti-CD105 CAR-T cells that displayed the typically activated cytotoxic T-cell characters,ability to proliferate,the production of pro-inflammatory cytokines,and the specific killing efficacy against CD105+target cells in vitro.The in vivo treatment with anti-CD105 CAR-T cells significantly inhibited the growth of implanted CD105+tumors,reduced tumor weight,and prolonged the survival time of tumor-bearing NOD/SCID mice.Nanobody-based CAR-T cells can therefore function as an antitumor agent in human tumor xenograft models.Our findings determined that the strategy of nanobody-based CAR-T cells engineered by CRISPR/Cas9 system has a certain potential to treat solid tumor through targeting CD105 antigen. | Fengzhen Mo Siliang Duan Xiaobing Jiang Xiaomei Yang Xiaoqiong Hou Wei Shi Cueva Jumbo Juan Carlos Aiqun Liu Shihua Yin Wu Wang Hua Yao Zihang Yu Zhuoran Tang Shenxia Xie Ziqiang Ding Xinyue Zhao Bruce D.Hammock Xiaoling Lu | 2021 | Signal Transduction and Targeted Therapy2021，6，3： | 2 |
| 17 | Prepara- tion of ZnO: Eu3+ nanospheres via a micro - emulsion method and analysis of the photoluminescence properties 显示文摘 | Zhao Shihua Du Xuelian Cui Yuting | 2014 | Journal of Nanoscience and Nanotechnology2014，14，5： | 1 |
| 18 | Mesenchymal stem cells hold promise for regenerative medicine显示文摘Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues.Mesenchymal stem cells(MSCs),a type of adult stem cell,have generated a great amount of interest over the past decade in this field.Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses.The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows:the capacity to differentiate into osteoblasts,chondrocytes,adipocytes,cardiomyocytes,hepatocytes,endothelial,and neuronal cells;the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation;the lack of immunogenicity;and the ability to perform immunomodulatory functions.In the present review,we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based.Furthermore,some pathological conditions under which the application of MSCs should be done with caution are also mentioned. | Shihua Wang Xuebin Qu Robert Chunhua Zhao | 2011 | Frontiers of Medicine2011，5，4： | 1 |
| 19 | Composite Nonlinear Bilateral Control for Teleoperation Systems With External Disturbances显示文摘This paper presents a new composite nonlinear bilateral control method based on the nonlinear disturbance observer(NDOB) for teleoperation systems with external disturbances. By introducing the estimations of NDOB and systems' nominal nonlinear dynamics into controller design, a NDOB based composite nonlinear bilateral controller is constructed to attenuate the influence of disturbance and uncertain nonlinearities. As compared with the existing bilateral control methods which usually achieve force haptic(i.e., contact force tracking)through a passive way, the newly proposed method has two major merits: 1) asymptotical convergence of both position and force tracking errors is guaranteed;2) disturbance influence on force tracking error dynamics is rejected through the direct feedforward compensation of disturbance estimation. Simulations on a nonlinear teleoperation system are carried out and the results validate the effectiveness of the proposed controller. | Zhenhua Zhao Jun Yang Shihua Li Wen-Hua Chen | 2019 | IEEE/CAA Journal of Automatica Sinica2019，6，5： | 1 |
| 20 | High accuracy object detection via bounding box regression network显示文摘As one of the primary computer vision problems, object detection aims to find and locate semantic objects in digital images. Different with object classification, which only recognizes an object to a certain class, object detection also needs to extract accurate locations of objects. In the state-of-the-art object detection algorithms, bounding box regression plays a critical role in order to achieve high localization accuracy. Almost all the popular deep learning based object detection algorithms have utilized bounding box regression for fine tuning of object locations. However, while bounding box regression is widely used, there is few study focused on the underlying rationale, performance dependencies, and performance evaluation. In this paper, we proposed a dedicated deep neural network for bounding box regression, and presented several methods to improve its performance. Some ad hoc experiments are conducted to prove the effectiveness of the network. Also, we apply the network as an auxiliary module to the faster R-CNN algorithm and test them on some real-world images. Experiment results show certain performance improvements on detection accuracy in term of mean IOU. | Lipeng SUN Shihua ZHAO Gang LI Binbing LIU | 2019 | Frontiers of Optoelectronics2019，12，3： | 1 |
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