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The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

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Protein & cell 2013年第6期4卷 445-455页

作者： Honggang Zhou Yuna Sun Ying Wang Min Liu Chao Liu Wenming Wang Xiang Liu Le Li Fei Deng Hualin Wang Yu Guo Zhiyong Lou College of Pharmacy and State Key Laboratory of Medicinal Chemical biology Nankai UniversityTianjin 300071China Laboratory of Structural biology and MOE Laboratory of Protein Science School of Medicine and Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China National Laboratory of Macromolecules Institute of BiophysicsChinese Academy of ScienceBeijing 100101China High-throughput Molecular Drug Discovery Center Tianjin Joint Academy of Biotechnology and MedicineTianjin 300457China

Severe fever with thrombocytopenia syndrome virus(SFTSV),a member of the Phlebovirus genus from the Bunyaviridae family endemic to China,is the causative agent of life-threatening severe fever with thrombocyto-penia syndrome(SFTS),which features high fever and *** to other negative-sense RNA viruses,SFTSV encodes a nucleocapsid protein(NP)that is essen-tial for viral *** facilitates viral RNA encapsida-tion and is responsible for the formation of ribonucleopro-tein ***,recent studies have indicated that NP from Phlebovirus members behaves in inhomogene-ous oligomerization *** the present study,we report the crystal structure of SFTSV NP at 2.8Åresolution and demonstrate the mechanism by which it processes a ring-shaped hexameric form to accomplish RNA *** residues essential for oligomerization are identi-fi ed through mutational analysis and identifi ed to have a signifi cant impact on RNA binding,which suggests that correct formation of highly ordered oligomers is a criti-cal step in RNA *** fi ndings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.

关键词： SFTSV nucleoprotein oligomer RNP as-sembly crystal structure

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Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1271-1287页

作者： Cancan Zheng Xiaomei Yu Yiyao Liang Yidong Zhu Yan He Long Liao Dingkang Wang Yanming Yang Xingfeng Yin Ang Li Qingyu He Bin Li MOE Key Laboratory of Tumor Molecular biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education institutes Institute of Life and Health EngineeringJinan UniversityGuangzhou 510632China Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hong Kong-Macao Institute of CNS RegenerationKey Laboratory of CNS RegenerationMinistry of EducationJinan UniversityGuangzhou 510632China MOE Key Laboratory of Tumor Molecular biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic MedicineInstitute of BiomedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China

As one of the hallmarks of cancer,metabolic reprogramming leads to cancer progression,and targeting glycolytic enzymes could be useful strategies for cancer *** screening a small molecule library consisting of 1320 FDA-approved drugs,we found that penfluridol,an antipsychotic drug used to treat schizophrenia,could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma(ESCC).Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of *** using drug affinity responsive target stability(DARTS)technology and proteomics,we identified phosphofructokinase,liver type(PFKL),a key enzyme in glycolysis,as a direct target of *** could not exhibit its anticancer property in PFKL-deficient cancer cells,illustrating that PFKL is essential for the bioactivity of *** PFKL expression is correlated with advanced stages and poor survival of ESCC patients,and silencing of PFKL significantly suppressed tumor ***,direct binding of penfluridol and PFKL inhibits glucose consumption,lactate and ATP production,leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent *** together,PFKL is a potential prognostic biomarker and therapeutic target in ESCC,and penfluridol may be a new therapeutic option for management of this lethal disease.

关键词： Drug repurposing Metabolic reprogramming Glycolysis PFKL DARTS technology Esophageal cancer Penfluridol

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3D spiral channels combined with flexible micro-sieve for high-throughput rare tumor cell enrichment and assay from clinical pleural effusion samples

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Bio-Design and Manufacturing 2022年第2期5卷 358-370页

作者： Jie Cheng Lina Zhang Yiran Zhang Yifei Ye Wenjie Zhao Lingqian Zhang Yuang Li Yang Liu Wenchang Zhang Hongyan Guo Mingxiao Li Yang Zhao Chengjun Huang institute of Microelectronics Chinese Academy of SciencesBeijing 100029China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China Department of cellular and Molecular biology Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China National Engineering Research Center for Beijing Biochip Technology Beijing 102206China

The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell *** this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned *** prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite *** by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural *** following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day *** above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.

关键词： cell enrichment High throughput Pleural effusion Liquid biopsy 3D printing

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Platelets prime hematopoietic-vascular niche to drive angiocrine-mediated liver regeneration

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Signal Transduction and Targeted Therapy 2017年第1期2卷 285-293页

作者： Koji Shido Deebly Chavez Zhongwei Cao Jane L Ko Shahin Rafii Bi-Sen Ding Division of Regenerative Medicine Department of MedicineAnsary Stem Cell InstituteWeill Cornell MedicineNew YorkNew YorkUSA Department of Biological Sciences Seton Hall UniversitySouth OrangeNew JerseyUSA

In mammals,the livers regenerate after chemical injury or resection of hepatic lobe by *** liver regeneration is initiated after mass loss remains to be *** we report that following liver injury,activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7+liver sinusoidal endothelial cell(LSEC)and VEGFR1^(+)myeloid cell,orchestrating hepatic *** carbon tetrachloride injection or hepatectomy,platelets and CD11b+VEGFR1^(+)myeloid cells were recruited to LSECs,and liver regeneration in both models was impaired in thrombopoietin-deficient(Thpo^(−/−))mice repressing production of circulating *** impeded regeneration phenotype was recapitulated in mice with either conditional ablation of Cxcr7 in LSEC(Cxcr7iΔ/iΔ)or Vegfr1 in myeloid cell(Vegfr1^(lysM/lysM)).Both Vegfr1lysM/lysM and Cxcr7i^(Δ/iΔ)mice exhibited suppressed expression of hepatocyte growth factor and Wnt2,two crucial trophogenic angiocrine factors instigating hepatocyte *** note,administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic *** such,our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine/angiocrine *** this‘hematopoietic–vascular niche’might help to develop regenerative therapy strategy for hepatic disorders.

关键词： hematopoietic impaired hepatic

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The long non-coding RNA DANA2 positively regulates drought tolerance by recruitingERF84 to promote JMJ29-mediated histone demethylation

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Molecular Plant 2023年第8期16卷 1339-1353页

作者： Pengxiang Zhang Reqing He Jun Yang Jingjing Cai Zhipeng Qu Rongxin Yang Jinbao Gu Zhen-Yu Wang David LAdelson Youlin Zhu Xiaofeng Cao Dong Wang Key Laboratory of Molecular biology and Gene Engineering in Jiangxi Province College of Life ScienceNanchang UniversityJiangxi 330031China State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100039China Department of Molecular and Biomedical Science School of Biological SciencesThe University of AdelaideAdelaideSA 5005Australia institute of Nanfan&Seed Industry Guangdong Academy of SciencesGuangdong 510316China

Tens of thousands of long non-coding RNAs have been uncovered in plants,but few of them have been comprehensively studied for their biological function and molecular mechanism of their mode of ***,we show that the Arabidopsis long non-coding RNA DANA2 interacts with an AP2/ERF transcription factor ERF84 in the cell nucleus and then affects the transcription of JMJ29 that encodes a Jumonji C domain-containing histone H3K9 *** RNA sequencing(RNA-seq)and genetic analyses demonstrate that DANA2 positively regulates drought stress responses through ***29 positively regulates the expression of ERF15 and GOLS2 by modulation of H3K9me2 ***,mutation of JMJ29 causes decreased ERF15 and GOLS2 expression,resulting in impaired drought tolerance,in agreement with drought-sensitive phenotypes of dana2 and erf84 *** together,these results demonstrate that DANA2 is a positive regulator of drought response and works jointly with the transcriptional activator ERF84 to modulate JMJ29 expression in plant response to drought.

关键词： long non-coding RNA H3K9 demethylase transcription factor drought response

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High-fidelity structured illumination microscopy by point-spread-function engineering

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Light(Science & Applications) 2021年第5期10卷 812-823页

作者： Gang Wen Simin Li Unbo Wang Xiaohu Chen Zhenglong Sun Yong Liang Xin Jin Yifan Xing Yaming jiu Yuguo Tang Hui Li Jiangsu Key Laboratory of Medical Optics CAS Center for Excellence in Molecular Cell ScienceSuzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhouJiangsu 215163China Academy for Engineering and Technology Fudan UniversityShanghai 200433China The Center for Microbes Development and HealthKey Laboratory of Molecular Virology and ImmunologyInstitute Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China

Structured illumination microscopy(SIM)has become a widely used tool for insight into biomedical challenges due to its rapid,long-term,and super-resolution(SR)***,artifacts that often appear in SIM images have long brought into question its fidelity,and might cause misinterpretation of biological *** present HiFi-SIM,a high-fidelity SIM reconstruction algorithm,by engineering the effective point spread function(PSF)into an ideal ***-SIM can effectively reduce commonly seen artifacts without loss of fine structures and improve the axial sectioning for samples with strong *** particular,HiFi-SIM is not sensitive to the commonly used PSF and reconstruction parameters;hence,it lowers the requirements for dedicated PSF calibration and complicated parameter adjustment,thus promoting SIM as a daily imaging tool.

关键词： HiFi illumination function

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Novel antidepressants targeting TREK1 channel

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中国药理学与毒理学杂志 2018年第9期32卷 729-730页

作者： LUO Qi-chao CHEN Li-ping CHENG Xi MA Yu-qin LI Xiao-na ZHANG Shi-lei LI Yang YANG Huai-yu State Key Laboratory of Drug Research and Key institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Shanghai Key Laboratory of Regulatory biology Institute of Biomedical Sciences and School of Life Sciences East China No

OBJECTIVE To find that the extracellular cap of a K2P channel can act as a new allosteric site and may serve as a direct drug *** Molecular biology and cell transfection,electrophysiology,molecular docking,molecular dynamics simulations,virtual screening for TREK1,and depressive-related behavior *** Extracellular domain of TREK1 channel existed a dynamic cavity in the extracellular domain by the method of computations,mutagenesis and *** dynamics simulations suggested that ligand-induced allosteric conformational transitions lead to blockage of the ion conductive *** virtual screening approach,we identified other inhibitors targeting the extracellular allosteric ligand-binding site of these ***,our results suggested that the allosteric site at the extracellular cap of the K2P channels might be a promising drug target for these membrane *** TREK1 inhibitor TKDC had significantly faster onset than that of fluoxetine in chronic administration trials,and the study confirms that TREK1 was an important target for the development of rapid *** The study is a significant step forward for understanding the function of TREK and for identifying specific inhibitors,which should be of interest to others in the field.

关键词： potassium channels target identification TREK1 inhibitor antidepressant effect

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Organization of long-range inputs and outputs of frontal cortex for top-down control

Organization of long-range inputs and outputs of frontal cor...

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中国神经科学学会第十二届全国学术会议

作者： Siyu Zhang Min Xu Wei-Cheng Chang Chenyan Ma Johnny Phong Hoang Do Daniel Jeong Tiffany Lei Jiang Lan Fan Yang Dan Discipline of Neuroscience Department of Anatomy Histology and Embryology and Collaborative Innovation Center for Brain Science Shanghai Jiao Tong University School of Medicine institute of Neuroscience State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Institutes for Biological Sciences CAS Division of Neurobiology Department of Molecular and Cell Biology Helen Wills Neuroscience Institute Howard Hughes Medical Institute University of California

Long-range projections from the frontal cortex are known to modulate sensory processing in multiple modalities. Although the mouse has become an increasingly important animal model for studying the circuit basis of behavior, the functional organization of its frontal cortical long-range connectivity remains poorly characterized. Here we used virus-assisted circuit mapping to identify the brain networks for top-down modulation of visual, somatosensory and auditory processing. The visual cortex is reciprocally connected to the anterior cingulate area, whereas the somatosensory and auditory cortices are connected to the primary and secondary motor cortices. Anterograde and retrograde tracing identified the cortical and subcortical structures belonging to each network. Furthermore, using new viral techniques to target subpopulations of frontal neurons projecting to the visual cortex versus the superior colliculus, we identified two distinct subnetworks within the visual network. These findings provide an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.

关键词： virus-assisted circuit mapping long-range projections visual network topdown control

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Fibroblasts:New players in the central nervous system?

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Fundamental Research 2024年第2期4卷 262-266页

作者： Lihui Duan Xiang Yu State Key Laboratory of Molecular Development biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Membrane biology School of Life SciencesPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences and Peking University McGovern institute Peking UniversityBeijing 100871China Chinese institute for Brain Research Beijing 102206China

Fibroblasts are typically described as cells that produce extracellular matrix,contribute to the formation of connective tissue,and maintain the structural framework of *** are the first cell type to be transdifferentiated into inducible pluripotent stem cells(iPSCs),demonstrating their versatility and ***,there is relatively extensive characterization of the anatomical,molecular,and functional diversity of fibroblasts in different peripheral organs and *** recent advances in single cell RNA sequencing,heterogeneity and diversity of fibroblasts in the central nervous system(CNS)have also begun to *** on their distinct anatomical locations in the meninges,perivascular space,and choroid plexus,as well as their molecular diversity,important roles for fibroblasts in the CNS have been ***,we draw inspirations from what is known about fibroblasts in peripheral tissues,in combination with their currently identified CNS locations and molecular characterizations,to propose potential functions of CNS fibroblasts in health and *** studies,using a combination of technologies,will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS.

关键词： Fibroblasts Central nervous system Infection Aging Neurodegenerative diseases Injury

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New paradigms on hematopoietic stem cell differentiation

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Protein & cell 2020年第1期11卷 34-44页

作者： Hui Cheng Zhaofeng Zheng Tao Cheng State Key Laboratory of Experimental Hematology Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina Center for Stem cell Medicine Chinese Academy of Medical SciencesTianjinChina Department of Stem cell and Regenerative Medicine Peking Union Medical CollegeTianjinChina

Ever since hematopoietic stem cells(HSCs)were first identified half a century ago,their differentiation roadmap has been extensively *** classical model of hematopoiesis has long held as a dogma that HSCs reside at the top of a hierarchy in which HSCs possess self-renewal capacity and can progressively give rise to all blood lineage ***,over the past several years,with advances in single cell technologies,this developmental scheme has been *** this review,we discuss the evidence supporting heterogeneity within HSC and progenitor populations as well as the hierarchical models revised by novel approaches mainly in mouse *** evolving views provide further understanding of hematopoiesis and highlight the complexity of hematopoietic differentiation.

关键词： hematopoietic stem cell hierarchy heterogeneity differentiation

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