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59篇 您的检索式:作者名="Jianan Xu"
    题名 作者 年代 出处 被引量
1Research and Practice of Blending Teaching Based on “MOOC + SPOC + Flipped Classroom” for Software Engineering显示文摘Based on 'MOOC + SPOC + Flipped Classroom', a particular blending teaching pattern adapting to MOOC teaching is proposed to strengthen software engineering students' abilities to study themselves and practice innovatively. Firstly, the process of MOOC development in China is introduced. The distinguishing feature and effect of MOOC teaching are analyzed, followed by the comparison with traditional class. The online Plus offline blending teaching pattern is the combination of online self-study on MOOC before class, seminar study of flipped classroom in class and the summary after class. With the demonstration of a typical case, a progressive strategy is given to implement blending teaching. Finally, the blending teaching pattern is assessed from multiple perspectives, of which both advantages and disadvantages are dissected. Through primary exploration, introducing online study and flipped classroom, blending teaching plays a positive role in software engineering teaching, which means traditional teaching pattern is changed. Meanwhile, students' innovative consciousness and practical ability are inspired. Nevertheless, new problems arise, so that intensive practice and improvement are necessary.Ce Zhang Dianhui Chu Songlin Gu Xiaofei Xu Jianan Jiang Zheng Wang Hua Zhang 2018计算机教育2018,,12:14
22D MOF Nanoflake-Assembled Spherical Microstructures for Enhanced Supercapacitor and Electrocatalysis Performances显示文摘Metal–organic frameworks(MOFs) are of great interest as potential electrochemically active materials.However, few studies have been conducted into understanding whether control of the shape and components of MOFs can optimize their electrochemical performances due to the rational realization of their shapes. Component control of MOFs remains a significant challenge. Herein, we demonstrate a solvothermal method to realize nanostructure engineering of 2D nanoflake MOFs. The hollow structures withNi/Co-and Ni-MOF(denoted as Ni/Co-MOF nanoflakes and Ni-MOF nanoflakes) were assembled for their electrochemical performance optimizations in supercapacitors and in the oxygen reduction reaction(ORR). As a result, the Ni/CoMOF nanoflakes exhibited remarkably enhanced performance with a specific capacitance of 530.4 F g^(-1)at 0.5 A g^(-1)in1 M LiO H aqueous solution, much higher than that of NiMOF(306.8 F g^(-1)) and ZIF-67(168.3 F g^(-1)), a good rate capability, and a robust cycling performance with no capacity fading after 2000 cycles. Ni/Co-MOF nanoflakes also showed improved electrocatalytic performance for the ORR compared to Ni-MOF and ZIF-67. The present work highlights the significant role of tuning 2D nanoflake ensembles of Ni/Co-MOF in accelerating electron and charge transportation for optimizing energy storage and conversion devices.Huicong Xia Jianan Zhang Zhao Yang Shiyu Guo Shihui Guo Qun Xu 2017Nano-Micro Letters2017,9,4:14
3Human infection with a further evolved avian H9N2 influenza A virus in Sichuan, China显示文摘Dear Editor,Avian influenza A (H9N2) virus plays a crucial role in interspecies transmission between animals and humans due to its wide host range, adaptation in mammals and the diversified gene reassortments. Since 1990s, two lineages of H9N2 virus, A/Duck/HK/Y280/97 (Y280-like)and A/Quail/HK/G1/97 (G1) have established in domestic poultry in China and are now widespread in theJianan Xu Shuang Li Yong Yang Bing Liu Huiping Yang Tiansu Li Lin Zhang Wei Li Xiaohu Luo Liquan Zhang Ming Pan 2018Science China(Life Sciences)2018,61,5:7
4Smart breeding driven by big data, artificial intelligence, and integrated genomic-enviromic prediction显示文摘The first paradigm of plant breeding involves direct selection-based phenotypic observation,followed by predictive breeding using statistical models for quantitative traits constructed based on genetic experimental design and,more recently,by incorporation of molecular marker genotypes.However,plant performance or phenotype(P)is determined by the combined effects of genotype(G),envirotype(E),and genotype by environment interaction(GEI).Phenotypes can be predicted more precisely by training a model using data collected from multiple sources,including spatiotemporal omics(genomics,phenomics,and enviromics across time and space).Integration of 3D information profiles(G-P-E),each with multidimensionality,provides predictive breeding with both tremendous opportunities and great challenges.Here,we first review innovative technologies for predictive breeding.We then evaluate multidimensional information profiles that can be integrated with a predictive breeding strategy,particularly envirotypic data,which have largely been neglected in data collection and are nearly untouched in model construction.We propose a smart breeding scheme,integrated genomic-enviromic prediction(iGEP),as an extension of genomic prediction,using integrated multiomics information,big data technology,and artificial intelligence(mainly focused on machine and deep learning).We discuss how to implement iGEP,including spatiotemporal models,environmental indices,factorial and spatiotemporal structure of plant breeding data,and cross-species prediction.A strategy is then proposed for prediction-based crop redesign at both the macro(individual,population,and species)and micro(gene,metabolism,and network)scales.Finally,we provide perspectives on translating smart breeding into genetic gain through integrative breeding platforms and open-source breeding initiatives.We call for coordinated efforts in smart breeding through iGEP,institutional partnerships,and innovative technological support.Yunbi Xu Xingping Zhang Huihui Li Hongjian Zheng Jianan Zhang Michael S.Olsen Rajeev K.Varshney Boddupalli M.Prasanna Qian Qian 2022Molecular Plant2022,15,11:7
5Quasi-phase-matching-division multiplexing holography in a three-dimensional nonlinear photonic crystal显示文摘Nonlinear holography has recently emerged as a novel tool to reconstruct the encoded information at a new wavelength,which has important applications in optical display and optical encryption.However,this scheme still struggles with low conversion efficiency and ineffective multiplexing.In this work,we demonstrate a quasi-phasematching(QPM)-division multiplexing holography in a three-dimensional(3D)nonlinear photonic crystal(NPC).3D NPC works as a nonlinear hologram,in which multiple images are distributed into different Ewald spheres in reciprocal space.The reciprocal vectors locating in a given Ewald sphere are capable of fulfilling the complete QPM conditions for the high-efficiency reconstruction of the target image at the second-harmonic(SH)wave.One can easily switch the reconstructed SH images by changing the QPM condition.The multiplexing capacity is scalable with the period number of 3D NPC.Our work provides a promising strategy to achieve highly efficient nonlinear multiplexing holography for high-security and high-density storage of optical information.Pengcheng Chen Chaowei Wang Dunzhao Wei Yanlei Hu Xiaoyi Xu Jiawen Li Dong Wu Jianan Ma Shengyun Ji Leran Zhang Liqun Xu Tianxin Wang Chuan Xu Jiaru Chu Shining Zhu Min Xiao Yong Zhang 2021Light(Science & Applications)2021,10,8:5
6In-situ Moissanite in Dunite: Deep Mantle Origin of Mantle Peridotite in Luobusa Ophiolite, Tibet显示文摘We report the discovery of an in-situ natural moissanite as an inclusion in the Cr-spinel from the dunite envelope of a chromitite deposit in Luobusa ophiolite, Tibet. The moissanite occurs as a twin crystal interpenetrated by two quadrilateral signal crystals with sizes of 17 μm× 10 μm and 20 μm× 7 μm, respectively. The moissanite is green with parallel extinction. The absorption peaks in its Raman spectra are at 967-971 cm-1, 787-788 cm-1, and 766 cm-1. The absorption peaks in the infrared spectra are at 696 cm-1, 767 cm-1, 1450 cm-1, and 1551 cm-1, which are distinctly different from the peaks for synthetic silicon carbide. Moissanites have been documented to form in ultra-high pressure, high temperature, and extremely low fO2 environments and their 13C-depleted compositions indicate a lower mantle origin. Combined with previous studies about other ultra-high pressure and highly reduced minerals in Luobusa ophiolite, the in-situ natural moissanite we found indicates a deep mantle origin of some materials in the mantle sequence of Luobusa ophiolite. Further, we proposed a transformation model to explain the transfer process of UHP materials from the deep mantle to ophiolite sequence and then to the supra-subduction zone environment. Interactions between the crown of the mantle plume and mid-ocean ridge are suggested to be the dominant mechanism.LIANG Fenghua XU Zhiqin ZHAO Jianan 2014Acta Geologica Sinica(English Edition)2014,88,2:5
7Development of high-resolution multiple-SNP arrays for genetic analyses and molecular breeding through genotyping by target sequencing and liquid chip显示文摘Genotyping platforms,as critical supports for genomics,genetics,and molecular breeding,have been well implemented at national institutions/universities in developed countries and multinational seed companies that possess high-throughput,automatic,large-scale,and shared facilities.In this study,we integrated an improved genotyping by target sequencing(GBTS)system with capture-in-solution(liquid chip)technology to develop a multiple single-nucleotide polymorphism(mSNP)approach in which mSNPs can be captured from a single amplicon.From one 40K maize mSNP panel,we developed three types of markers(40K mSNPs,251K SNPs,and 690K haplotypes),and generated multiple panels with various marker densities(1K–40K mSNPs)by sequencing at different depths.Comparative genetic diversity analysis was performed with genic versus intergenic markers and di-allelic SNPs versus non-typical SNPs.Compared with the one-amplicon-one-SNP system,mSNPs and within-mSNP haplotypes are more powerful for genetic diversity detection,linkage disequilibrium decay analysis,and genome-wide association studies.The technologies,protocols,and application scenarios developed for maize in this study will serve as a model for the development of mSNP arrays and highly efficient GBTS systems in animals,plants,and microorganisms.Zifeng Guo Quannv Yang Feifei Huang Hongjian Zheng Zhiqin Sang Yanfen Xu Cong Zhang Kunsheng Wu Jiajun Tao Boddupalli MPrasanna Michael SOlsen Yunbo Wang Jianan Zhang Yunbi Xu 2021Plant Communications2021,2,6:5
8Recent Progress on Two-Dimensional Nanoflake Ensembles for Energy Storage Applications显示文摘The rational design and synthesis of two-dimensional(2D) nanoflake ensemble-based materials have garnered great attention owing to the properties of the components of these materials, such as high mechanical flexibility, high specific surface area, numerous active sites,chemical stability, and superior electrical and thermal conductivity. These properties render the 2D ensembles great choices as alternative electrode materials for electrochemical energy storage systems. More recently,recognition of the numerous advantages of these 2D ensemble structures has led to the realization that the performance of certain devices could be significantly enhanced by utilizing three-dimensional(3D) architectures that can furnish an increased number of active sites. The present review summarizes the recent progress in 2D ensemble-based materials for energy storage applications,including supercapacitors, lithium-ion batteries, and sodium-ion batteries. Further, perspectives relating to the challenges and opportunities in this promising research area are discussed.Huicong Xia Qun Xu Jianan Zhang 2018Nano-Micro Letters2018,10,4:4
9An electrodeposition approach to metal/metal oxide heterostructures for active hydrogen evolution catalysts in near-neutral electrolytes显示文摘Neutral water splitting is attractive for its use of non-corrosive and environmentally friendly electrolytes.However,catalyst development for hydrogen and oxygen evolution remains a challenge under neutral conditions.Here we report a simple electrodeposition and reductive annealing procedure to produce a highly active Ni-Co-Cr metal/metal oxide heterostructured catalyst directly on Ni foam.The resulting electrocatalyst for hydrogen evolution reaction (HER) requires only 198 mV of overpotential to reach 100 mNcm2 in 1 M potassium phosphate (pH =7.4) and can operate for at least two days without significant performance decay.Scanning transmission electron microscopy coupled with electron energy loss spectroscopy (STEM-EELS) imaging reveals a Ni-Co alloy core decorated with blended oxides layers of NiO,CoO and Cr2O3.The metal/metal oxide interfaces are suggested to be responsible for the high HER activity.Michael J.Kenney Jianan Erick Huang Yong Zhu Yongtao Meng Mingquan Xu Guanzhou Zhu Wei-Hsuan Hung Yun Kuang Mengchang Lin Xiaoming Sun Wu Zhou Hongjie Dai 2019Nano Research2019,12,6:4
10Highly efficient difference-frequency generation for mid-infrared pulses by passively synchronous seeding显示文摘We have proposed and experimentally demonstrated a novel scheme for efficient mid-infrared difference-frequency generation based on passively synchronized fiber lasers. The adoption of coincident seeding pulses in the nonlinear conversion process could substantially lower the pumping threshold for mid-infrared parametric emission. Consequently,a picosecond mid-infrared source at 3.1 μm was prepared with watt-level average power, and a maximum power conversion efficiency of 77% was realized from pump to down-converted light. Additionally, the long-term stability of generated power was manifested with a relative fluctuation as low as 0.17% over one hour. Thanks to the all-optical passive synchronization and all-polarization-maintaining fiber architecture, the implemented laser system was also featured with simplicity, compactness and robustness, which would favor subsequent applications beyond laboratory operation.Kun Huang Yinqi Wang Jianan Fang Huaixi Chen Minghang Xu Qiang Hao Ming Yan Heping Zeng 2021High Power Laser Science and Engineering2021,9,1:4
11Fabrication of Fe-doped Co-MOF with mesoporous structure for the optimization of supercapacitor performances显示文摘The synergy effect between different components has attracted widespread attentions because of improved activity, selectivity and stability than single component. In this paper, we fabricated mesoporous hybrid dual-metal Co and Fe containing metallic organic framework(Co/Fe-MOF), Fe-MOF,and Co-MOF in the ionic liquid(IL)/supercritical CO2(SC)/surfactant emulsion system, and then studied the electrochemical properties of the three MOFs systematically. Experiment results indicate that, by taking advantages of coexistence of double metal, hybrid bi-metal Co/Fe-MOF exhibits the highest specific capacitance and the best cycling stability, with specific capacitance to 319.5 F/g at 1 A/g, 1.4 and 4 times for single Co-MOF and Fe-MOF, respectively.Huanan Yu Huicong Xia Jianan Zhang Jing He Shiyu Guo Qun Xu 2018Chinese Chemical Letters2018,29,6:4
12New possible silver lining for pancreatic cancer therapy:Hydrogen sulfide and its donors显示文摘As one of the most lethal diseases,pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities.Furthermore,pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found.Although combinations of new drugs,multimodal therapies,and adjuvants prolong survival,most patients still relapse after surgery and eventually die.Consequently,the search for more effective treatments for pancreatic cancer is highly relevant and justified.As a newly re-discovered mediator of gasotransmission,hydrogen sulfide(H2S)undertakes essential functions,encompassing various signaling complexes that occupy key processes in human biology.Accumulating evidence indicates that H2S exhibits bimodal modulation of cancer development.Thus,endogenous or low levels of exogenous H2S are thought to promote cancer,whereas high doses of exogenous H2S suppress tumor proliferation.Similarly,inhibition of endogenous H2S production also suppresses tumor proliferation.Accordingly,H2S biosynthesis inhibitors and H2S supplementation(H2S donors)are two distinct strategies for the treatment of cancer.Unfortunately,modulation of endogenous H2S on pancreatic cancer has not been studied so far.However,H2S donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation,inducing apoptosis,arresting cell cycle,and suppressing invasion and migration through exploiting multiple signaling pathways.As far as we know,there is no review of the effects of H2S donors on pancreatic cancer.Based on these concerns,the therapeutic effects of some H2S donors and NO-H2S dual donors on pancreatic cancer were summarized in this paper.Exogenous H2S donors may be promising compounds for pancreatic cancer treatment.Xu Hua Yan Xiao Jianan Sun Bao Ji Shanshan Luo Bo Wu Chao Zheng Peng Wang Fanxing Xu Keguang Cheng Huiming Hua Dahong Li 2021Acta Pharmaceutica Sinica B2021,11,5:4
13Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome显示文摘Dear Editor, Most disease-associated genomic mutations are base substitutions and approximately half of pathogenic human single nucleotide polymorphisms (SNPs)are related to C-to-T substitutions in the ClinVar database.Base editors (BEs),which combine Casg-DIOA nickase and APOBEC (apolipoprotein B mRNA editing enzyme,catalytic polypeptide-like)or AID (activation-induced deaminase)cytidine deaminase family members, have been successfully applied to mediate C-to-T conversion in vitro and in vivo, providing a powerful tool to model or repair diseaserelated human SNPs.Jianan Li Zhen Liu Shisheng Huang Xiao Wang Guanglei Li Yuting Xu Wenxia Yu Shanshan Chen Yu Zhang Hanhui Ma Zunfu Ke Jia Chen Qiang Sun Xingxu Huang 2019Cell Research2019,29,2:3
14Comparative Study of Acid and Alkaline Stimulants with Granite in an Enhanced Geothermal System显示文摘The Enhanced Geothermal System(EGS) is an artificial geothermal system that aims to economically extract heat from hot dry rock(HDR) through the creation of an artificial geothermal reservoir. Chemical stimulation is thought to be an effective method to create fracture networks and open existing fractures in hot dry rocks by injecting chemical agents into the reservoir to dissolve the minerals. Granite is a common type of hot dry rock. In this paper, a series of chemical stimulation experiments were implemented using acid and alkaline agents under high temperature and pressure conditions that mimic the environment of formation. Granite rock samples used in the experiments are collected from the potential EGS reservoir in the Matouying area, Hebei, China. Laboratory experimental results show that the corrosion ratio per unit area of rock is 3.2% in static acid chemical experiments and 0.51% in static alkaline chemical experiments. The permeability of the core is increased by 1.62 times in dynamic acid chemical experiments and 2.45 times in dynamic alkaline chemical experiments. A scanning electron microscope analysis of the core illustrates that secondary minerals, such as chlorite, spherical silica, and montmorillonite, were formed, due to acid-rock interaction with plagioclase being precipitated by alkaline-rock interactions. Masking agents in alkaline chemical agents can slightly reduce the degree of plagioclase formation. A chemical simulation model was built using TOUGHREACT, the mineral dissolution and associated ion concentration variation being reproduced by this reactive transport model.XU Jianan FENG Bo CUI Zhenpeng LIU Xiyao KE Zunsong FENG Guanhong 2021Acta Geologica Sinica(English Edition)2021,95,6:2
15Assessing the genetic diversity of the critically endangered Chinese sturgeon Acipenser sinensis using mitochondrial markers and genome-wide single-nucleotide polymorphisms from RAD-seq显示文摘As a living fossil, the endangered Chinese sturgeon(Acipenser sinensis) has been considered a national treasure in China. Here,the famous Gezhouba Dam and Three Gorges Dam on the Yangtze River were built in 1988 and 2006, for economic purposes.The natural population of Chinese sturgeon has declined since then, as these dams block its migratory route to the original spawning grounds in the middle reaches of the Yangtze River. In 2013 and 2014, there was an absence of spawning where it typically happened near the Gezhouba Dam. Nevertheless, from April to June in 2015, over 1,000 larvae with different body lengths(10–35 cm) were detected along the Shanghai Yangtze Estuary; but only little is currently known about the population genetic structure of the Chinese sturgeon. Herein, we inferred population genetic parameters from 462 available Chinese sturgeon specimens based on a 421-bp fragment of the mitochondrial DNA(mtDNA) D-loop region and 1,481,620 SNPs(singlenucleotide polymorphisms) generated by restriction site-associated DNA sequencing(RAD-seq). For the D-loop dataset, 15 haplotypes were determined. Randomly picked 23 individuals, representing the 15 D-loop haplotype groups, were subsequently used for further RAD-seq validation. The average nucleotide diversity calculated from the mtDNA and RAD datasets was 0.0086 and 0.000478, respectively. The overall effective female population size was calculated to be 1,255 to 2,607, and the long-term effective population size was estimated to range from 11,950 to 119,500. We observed that the genetic variability and the effective female population size of the current population in the Yangtze River are severely low, which are similar to the data reported over 10 years ago. The deduced relatively small effective population of female fish, limiting the genetic connectivity among Chinese sturgeon, should be considered a serious threat to this endangered species.Jian Liu Xinxin You Pao Xu Ping Zhuang Yueping Zheng Kai Zhang Min Wang Yunyun Lv Gangchun Xu Feng Zhao Jianhui Wu Houyong Fan Jianan Xu Zhiqiang Ruan Chao Bian Kai Liu Dongpo Xu Jinhui Chen Junmin Xu Qiong Shi 2018Science China(Life Sciences)2018,61,9:2
16A Case Study of Applying Metagenomic Sequencing in Precise Epidemiology for the COVID-19 Pandemic-Sichuan Province, China, 2020显示文摘Introduction:Determining the transmission chain of a virus in its incipient stages is extremely time consuming in traditional approaches that rely mainly on case incidence and interview-based contact data.With the development of high-throughput sequencing technology,genome-based epidemiology approach is showing promise in detecting viral transmission.However,there is still insufficient evidence for the relationship between the viral genetic variations and real viral transmission.Methods:To explore the possible relationship between transmission chains and viral genetic variations,we combined both epidemiological data and viral genomes of COVID-19 virus collected from Sichuan Province.A phylogenetic approach was used to infer the transmission chain,which was then compared to the transmission chain that came from epidemiological data.Results:We found that the putative transmission chains were highly concordant to the true transmission chains from epidemiological data,suggesting a strong correlation between viral genetic variations and the viral transmission chain.Discussion:Our results showed advantages of viral genomic sequencing in tracking and perceiving pathogen transmission,which allowed for potential improvements in the design and implementation of population-level public health interventions.Jianan Xu Ye Wang You Li Huiping Yang Ming Pan Jian Liu Lina Shi Yuliang Feng Li Liu Jin Li Li Zhang Shusen He 2020China CDC weekly2020,2,47:2
17Five Independent Cases of Human Infection with Avian Influenza H5N6—Sichuan Province,China,2021显示文摘Summary What is known about this topic?The emerging H5Ny lineages of the avian influenza virus(AIV)with genomic reassortments have posed a continuous threat to animals and human beings.Since the first case of avian influenza A(H5N6)virus infection in 2014,the World Health Organization has reported a total of 38 cases by August 6,2021.Chongkun Xiao Jianan Xu Yu Lan Zhongping Huang Lijun Zhou Yaxin Guo Xiyan Li Lei Yang George F.Gao Dayan Wang William J.Liu Xingyu Zhou Huiping Yang 2021China CDC weekly2021,3,36:2
18The Effect of CD3-Specific Monoclonal Antibody on Treating Experimental Autoimmune Myasthenia Gravis显示文摘CD3-specific monoclonal antibody was the first one used for clinical practice in field of transplantation. Recently,renewed interests have elicited in its capacity to prevent autoimmune diabetes by inducing immune tolerance. In this study, we tested whether this antibody can also be used to treat another kind of autoimmune disease myasthenia gravis (MG) and explored the possible mechanisms. MG is caused by an autoimmune damage mediated by antibody- and complement-mediated destruction of AChR at the neuromuscular junction. We found that administration of CD3-specific antibody (Fab)2 to an animal model with experimental autoimmune myasthenia gravis (EAMG) (B6 mice received 3 times of AChR/CFA immunization) could not significantly improve the clinical signs and clinical score. When the possible mechanisms were tested, we found that CD3 antibody treatment slightly down-regulated the T-cell response to AChR, modestly up-regulation the muscle strength. And no significant difference in the titers of IgG2b was found between CD3 antibody treated and control groups. These data indicated that CD3-specific antibody was not suitable for treating MG, an antibody- and complementmediated autoimmune disease, after this disease has been established. The role of CD3-specific antibody in treating this kind of disease remains to be determined.Ruonan Xu~1 Jianan Wang~1 Guojiang Chen~1 Gencheng Han~1 Renxi Wang~1 Beifen Shen~1 Yan Li~(1,2) ~1Institute of Basic Medical Science,Academy of military Medical Science,Beijing 100850,China ~2Department of Molecular Immunology,Institute of Basic Medical Science,27 Taiping Road,Beijing 100850,China. 2005Cellular & Molecular Immunology2005,2,6:2
19CRISPR-Cas adaptive immune systems in Sulfolobales:genetic studies and molecular mechanisms显示文摘CRISPR-Cas systems provide the small RNA-based adaptive immunity to defend against invasive genetic elements in archaea and bacteria.Organisms of Sulfolobales,an order of thermophilic acidophiles belonging to the Crenarchaeotal Phylum,usually contain both type I and typeⅢCRISPR-Cas systems.Two species,Saccharolobus solfataricus and Sulfolobus islandicus,have been important models for CRISPR study in archaea,and knowledge obtained from these studies has greatly expanded our understanding of molecular mechanisms of antiviral defense in all three steps:adaptation,expression and crRNA processing,and interference.Four subtypes of CRISPR-Cas systems are common in these organisms,including I-A,I-D,Ⅲ-B,andⅢ-D.These cas genes form functional modules,e.g.,all genes required for adaptation and for interference in the I-A immune system are clustered together to form aCas and i Cas modules.Genetic assays have been developed to study mechanisms of adaptation and interference by different CRISPR-Cas systems in these model archaea,and these methodologies are useful in demonstration of the protospacer-adjacent motif(PAM)-dependent DNA interference by I-A interference modules and multiple interference activities byⅢ-B Cmr systems.Ribonucleoprotein effector complexes have been isolated for SulfolobalesⅢ-B andⅢ-D systems,and their biochemical characterization has greatly enriched the knowledge of molecular mechanisms of these novel antiviral immune responses.Zhenxiao Yu Suping Jiang Yuan Wang Xuhui Tian Pengpeng Zhao Jianan Xu Mingxia Feng Qunxin She 2021Science China(Life Sciences)2021,64,5:2
20Epigenetic drug library screening identified an LSD1 inhibitor to target UTX-deficient cells for differentiation therapy显示文摘UTX(also known as KDM6A),a histone 3 lysine 27 demethylase,is among the most frequently mutated epigenetic regulators in myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML).Recent studies have suggested that UTX mutations promote MDS and AML by blocking the differentiation of hematopoietic stem and progenitor cells(HSPCs).Here,we performed an epigenetic drug library screening for small molecules able to release the differentiation block on HSPCs induced by UTX deficiency.We found that SP2509,a selective inhibitor of LSD1,specifically promoted the differentiation of Utx-null HSPCs while sparing wild-type HSPCs.Transcriptome profiling showed that Utx loss reduced the expression of differentiation-related and tumor suppressor genes,correlating with their potential roles in HSPC self-renewal and leukemogenesis.In contrast,SP2509 treatment reversed these changes in gene expression in Utx-null HSPCs.Accordingly,Utx loss decreased H3K4 methylation level probably through the COMPASS-like complex,while LSD1 inhibition by SP2509 partially reversed the reduction of H3K4 methylation in Utx-deficient HSPCs.Further,SP2509 promoted the differentiation of Utx-null AML cells in vitro and in vivo and,therefore,extended the survival of these leukemic mice.Thus,our study identified a novel strategy to specifically target both premalignant and malignant cells with Utx deficiency for differentiation therapy and provided insights into the molecular mechanisms underlying the role of Utx in regulating HSPCs and related diseases.Baohong Wu Xiangyu Pan Xuelan Chen Mei Chen Kaidou Shi Jing Xu Jianan Zheng Ting Niu Chong Chen Xiao Shuai Yu Liu 2019Signal Transduction and Targeted Therapy2019,4,1:2
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