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An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

Signal Transduction and Targeted Therapy 2021年第5期6卷 1585-1600页

作者： Yiyue Ge Tingzhong Tian Suling Huang Fangping Wan Jingxin Li Shuya Li Xiaoting Wang Hui Yang Lixiang Hong Nian Wu Enming Yuan Yunan Luo Lili Cheng Chengliang Hu Yipin Lei Hantao Shu Xiaolong Feng Ziyuan Jiang Yunfu Wu Ying Chi Xiling Guo Lunbiao Cui Liang Xiao Zeng Li Chunhao Yang Zehong Miao Ligong Chen Haitao Li Hainian Zeng Dan Zhao Fengcai Zhu Xiaokun Shen Jianyang Zeng Institute for Interdisciplinary Information Sciences Tsinghua UniversityBeijingChina NHC Key laboratory of Emeric Pathogenic Microbiology Jiangsu Provincial Center for Diseases Control and PreventionNanjingJiangsu ProvinceChina Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghaiChina Silexon Al Technology Co. Ltd.NanjingJiangsu ProvinceChina Department of Computer Science University of Illinois at Urbana-ChampaignIllinoisILUSA School of Pharmaceutical Sciences Tsinghua UniversityBeijingChina School of Electronic Information and Communications Huazhong University of Science and TechnologyWuhanHubei ProvinceChina Institute of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Automation Tsinghua UniversityBeijingChina Inner Mongolia Alashan League Organization Establishment Committee Office Electronic Support Center AlashanInner MongoliaChina Convalife(Shanghai)Co. Ltd.ShanghaiChina Advanced Innovation Center for Human Brain Protection Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Beijing Advanced Innovation Center for Structural Biology Tsinghua-Peking Joint Center for Life SciencesDepartment of Basic Medical SciencesSchool of MedicineTsinghua UniversityBeijingChina Center for Global Health Nanjing Medical UniversityNanjingJiangsu ProvinceChina

The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed an integrative drug repositioning framework,which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph,literature and transcriptome data to discover the potential drug candidates against *** in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1(PARP1)inhibitor,CVL218,currently in Phase I clinical trial,may be repurposed to treat *** in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic *** addition,we showed that CVL218 can interact with the nucleocapsid(N)protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.

关键词： prevention respiratory acute

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Downregulation of forkhead box O1 (FOXO1) acetylation ameliorates cognitive dysfunction by inhibiting endoplasmic reticulum stress-regulated neuronal apoptosis in APP/PS1 transgenic mice

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Neuroprotection 2025年第0期

作者： Zhang, Nan Zhao, Zongyuan Chen, Xiaoxiao Yao, Hanbing Zhu, Min Ma, Shuqing Wang, Hui Yin, Xianghong Zhou, Ying Zheng, Chenfei Li, Jianmin Pan, Jingye Wang, Kaicheng Yang, Bin Wang, Yunting Fan, Junming Gong, Yongsheng Liu, Rong Zeng, Jing Fan, Xiaofang Shentu, Yangping School of Basic Medical Sciences Institute of Hypoxia Medicine Wenzhou Medical University Zhejiang Wenzhou China Wenzhou Medical University Zhejiang Wenzhou China Department of Pathology The First Affiliated Hospital of Wenzhou Medical University Zhejiang Wenzhou China Department of Nephrology The First Affiliated Hospital of Wenzhou Medical University Zhejiang Wenzhou China Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province Zhejiang Wenzhou China Department of Intensive Care Unit The First Affiliated Hospital of Wenzhou Medical University Zhejiang Wenzhou China Wenzhou Key Laboratory of Critical Care and Artificial Intelligence Zhejiang Wenzhou China Department of Laboratory Medicine West China Hospital Sichuan University Sichuan Chengdu China Department of Pharmacological and Pharmaceutical Sciences College of Pharmacy University of Houston Houston TX United States Department of Pathophysiology Key Laboratory of Ministry of Education for Neurological Disorders School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Hubei Wuhan China Key Laboratory of Alzheimer's Disease of Zhejiang Province Zhejiang Wenzhou China Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation First Affiliated Hospital Wenzhou Medical University Zhejiang Wenzhou China Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical University Zhejiang Wenzhou China

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that affects the central nervous system. Silent information regulator sirtuin 1 (SIRT1) may deacetylate and suppress forkhead box O (FOXO) activities to promote neuronal survival. FOXO1 is involved in the regulation of metabolism, senescence, stress response, and apoptosis. Moreover, endoplasmic reticulum stress (ERS) mediates cell apoptosis. Therefore, this study aimed to determine whether the downregulation of SIRT1 expression exacerbates cognitive dysfunction by activating FOXO1 acetylation and promoting ERS-mediated apoptosis in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice. Methods: We used APP/PS1 transgenic mice to construct an in vivo AD model. Additionally, we used β-amyloid (Aβ)-incubated HT22 cells and primary neurons (PNs) for in vitro analyses. Cognitive function was assessed using novel object recognition, the Morris water maze, and fear conditioning. Discrepancies between wild-type (WT) and APP/PS1 transgenic mice were evaluated using an unpaired t test. In addition, one-way analysis of variance was conducted for behavioral assessments and other tests involving four distinct groups, followed by a Tukey's honestly significant difference test for post hoc pairwise comparisons. Results: The expression of SIRT1 was downregulated (in animal experiments, WT mice vs. APP/PS1 mice, n = 3, p = 0.002;in cell experiments, HT22 cells vs. HT22 cells + Aβ_1–42, n = 3, p = 0.001;primary neurons vs. primary neurons + Aβ₁₋₄₂, n = 3, p < 0.001), whereas FOXO1 acetylation was upregulated both in vivo and in vitro (in animal experiments, WT mice vs. APP/PS1 mice, n = 3, p < 0.001;in cell experiments, HT22 cells vs. HT22 cells + Aβ₁₋₄₂, n = 3, p = 0.004;primary neurons vs. primary neurons + Aβ_1–42, n = 3, p < 0.001), leading to cognitive dysfunction, Aβ plaque deposition, and neuronal apoptosis. Quercetin, a SIRT1 agonist, reversed these chang

关键词： acetylation Alzheimer's disease endoplasmic reticulum stress forkhead box protein O1 neuronal apoptosis sirtuin 1

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Effects of Geometric Parameters on Performance of Rectangular Submerged Inlet for Aircraft

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Transactions of Nanjing University of Aeronautics and Astronautics 2021年第6期38卷 984-992页

作者： LIU Chao PEI Houju CHEN Changdong XU Wenbing YANG Kaijie Environment Control and Oxygen System Department Shanghai Aircraft Design and Research InstituteShanghai 201210P.R.China AVIC Nanjing Servo Control System Corporation Nanjing 210016P.R.China College of Energy&Power Engineering Jiangsu University of Science and TechnologyZhenjiang 212003P.R.China Key Laboratory of Aircraft Environment Control and Life Support MIITNanjing University of Aeronautics and AstronauticsNanjing 210016P.R.China

To improve the comfortability and safety of aircraft,the demand of rectangular submerged inlets(RSIs)with low resistance is proposed to increase the inlet flow rate of ram air. A theoretical model is built to numerically analyze the effects of geometric parameters on the inlet mass flow rate of RSIs. The geometric parameters in question here encompass the aspect ratio of 2—4,the ramp angle of 6°—7°,the characteristic parameter of the throat of 0.20 —0.30,the ramp length of 939—1 337 mm,and the cone angle of 0° —3°. Simulation results demonstrate that the mass flow rate(MFR)is positively correlated with the aspect ratio,ramp angle,ramp length,and cone angle,and negatively correlated with characteristic parameter of the throat. Within the range of the geometric parameters considered,the RSI with the aspect ratio of 3,the ramp angle of 6°,the characteristic parameter of the throat of 0.20,the ramp length of 1 337 mm,and the cone angle of 3° obtains the largest MFR value of about 2.251 kg/s.

关键词： ram air system rectangular submerged inlet geometric parameter mass flow rate(MFR)

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Numerical study of thermal-hydraulic performances of microchannel heat sinks with different channel structures

Numerical study of thermal-hydraulic performances of microch...

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CSAA/IET International Conference on Aircraft Utility Systems (AUS 2020)

作者： G. Zhang Y. Xu Q. Dai Nanjing University of Science and Technology School of Energy and Power Engineering Nanjing China Nanjing University of Aeronautics and Astronautics Key Laboratory of Aircraft Environment Control and Life Support MIIT Nanjing China

Numerical simulations were carried out to investigate the thermal-hydraulic characteristics of water flowing through different heat sinks. Calculations show that the internal fin structure of the heat sink has an important influence on the flow resistance and heat transfer. The zigzag channel has the largest flow resistance, while the straight channel has the smallest flow resistance, but the heat transfer capacity is opposite. In addition, the performance of heat sinks when inserting pin fins with different shapes in straight channels was also compared. The results show that the thermal resistance of circular pin fins is the smallest.

关键词： heat transfer numerical analysis heat sinks microchannel flow thermal resistance

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Effects of long term isolation on the emotion change of ‘‘Lunar Palace 365” crewmembers

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science Bulletin 2019年第13期64卷 881-884页

作者： Zikai Hao Yinzhen Zhu Siyuan Feng Chen Meng Dawei Hu Hui Liu Hong Liu Beijing Advanced Innovation Centre for Biomedical Engineering Beihang UniversityBeijing 102402China Institute of Environmental Biology and Life Support Technology School of Biological Science and Medical EngineeringBeihang UniversityBeijing 100083China State Key Laboratory of Virtual Reality Technology and Systems School of Computer Science and EngineeringBeihang UniversityBeijing 100083China International Joint Research Center of Aerospace Biotechnology & Medical Engineering. Beihang University Beijing 100083China

The psychological health risk is one of the most serious and difficult risks to mitigate during manned deep space exploration[1].In a space capsule or station,the environment is isolated,and communication with the outside is limited to telephone or delayed *** monotonous working schedule also aggravates loneliness and homesickness,which could trigger negative moods,such as depression and ***,an astronaut’s unstable emotional state could be a threat to the safety and performance of a space mission.

关键词： Effects schedule trigger most is be

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Numerical simulation on flow boiling characteristics in sinusoidal channels of airborne micro heat exchanger

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Journal of Physics: Conference Series 2022年第1期2228卷

作者： Xingzhuang Liang Yu Xu Jian Wang State Key Laboratory of Fire Science University of Science and Technology of China Hefei 230026 China AVIC Shenyang Aircraft Design & Research Institute Shenyang 110035 China Key Laboratory of Aircraft Environment Control and Life Support MIIT Nanjing University of Aeronautics and Astronautics Nanjing 210016 China.

With the miniaturization of airborne system, heat dissipation has become a critical issue. Since sinusoidal channel can enhance flow disturbance, it has a stronger heat exchange capacity than that of straight channel. However, flow boiling characteristics in sinusoidal channel are more complex. Here, numerical simulations of flow boiling in sinusoidal and straight microchannels are conducted based on the VOF model with the inner diameter of 1 mm, mass flux of 500 kg/m2 s and heat flux of 50 kW/m2. The effects of channel structure and hypergravity are obtained. The simulation results indicate that bubble evolution in sinusoidal channel is more complex than that in straight channel, and bubbles are more likely to coalesce, deform and break. Vortices appear in sinusoidal channel and disrupt the near-wall boundary layer. Bubble evolution combined with vortices affect the flow boiling performances. For straight channel, dryout is less likely to occur, while for sinusoidal channel, it is more likely due to more drastic flow changes. Furthermore, the transition of flow patterns is faster under hypergravity. For sinusoidal channel, flow patterns transform earlier into slug and circular flows.

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Preparation of biodegradable PLA/PCL composite filaments: effect of PLA content on strength

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IOP Conference Series: Materials science and Engineering 2020年第1期770卷

作者： H M Qiu K W Hou J P Zhou W J Liu J B Wen Q F Gu School of Material Science and Engineering Nanchang Hangkong University Nanchang 330063 China Aviation Key Laboratory of Science and Technology on Life-Support Technology Xiangyang 441000 China

As one of the predominant 3D additive manufacturing technology, fused deposition modeling (FDM) suffers from the rich printable filaments. The goal of this paper is to produce a fully biodegradable polymeric composite filament by blending polylactic acid (PLA) with polycaprolactone (PCL). The effect of PCL content on the geometry, size, roughness and ultimate tensile stress of PLA/PCL composite filaments was investigated, and mechanical properties of the printed components were tested. The results indicate that, with the increase of PCL content, the diameter and ultimate tensile stress gradually decreased, while the surface roughness gradually increased. Due to the toughing effect, with an increase in PCL content, the tensile strength of parts decreased, while the elongation at break and the impact strength kept rising. It was found the parts printed with the addition of 20% of PCL composite filament exhibits the optimal comprehensive performance.

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Numerical investigation of influence of structure and operating parameters on performance of vortex oil filter

Numerical investigation of influence of structure and operat...

引用

CSAA/IET International Conference on Aircraft Utility Systems, AUS 2018

作者： Wang, Ning Chen, Weijian Ning, Guoli Hui, Ma Key Laboratory of Aircraft Environment Control and Life Support MIIT Nanjing University of Aeronautics and Astronautics Nanjing China Aviation Key Laboratory of Science and Technology on Aero Electromechanical System Integration Nanjing China

ISBN: (纸本)9781785617911

In this paper, the three-dimensional numerical simulation of solid-liquid two-phase flow in a vortex oil filter is performed by means of numerical simulation. The Reynolds stress turbulence model is used in the simulation flow field, and the DPM model is used for solid particle tracking. The influence of key structural parameters and operating parameters on the filtering effect was mainly studied, such as the inlet width, the size of the overflow pipe, the wall thickness and the insertion depth, the size of the cone angle and the length of the cone end. The results provide the basis for the rational design of the vortex oil filter. © 2018 IET Conference Publications. All rights reserved.

关键词： Vortex flow

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Neural-activity-regulated and glia-mediated control of brain lymphatic development

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Cell 2025年

作者： Li, Jia Liu, Ming-Jian Du, Wen-Jie Peng, Xiao-Lan Deng, Hao Zi, Hua-Xing Shang, Han-Bing Du, Jiu-Lin Institute of Neuroscience Key Laboratory of Brain Cognition and Brain-Inspired Intelligence Technology Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai 200031 China University of Chinese Academy of Sciences Beijing 100049 China Department of Neurosurgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Anesthesiology Huashan Hospital Fudan University Shanghai 200040 China Emergency Medicine Center Shanghai Institute of Aviation Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China School of Life Science and Technology ShanghaiTech University Shanghai 200031 China Department of Neurosurgery Huashan Hospital Fudan University Shanghai 200040 China

The nervous system regulates peripheral immune responses under physiological and pathological conditions, but the brain's impact on immune system development remains unknown. Meningeal mural lymphatic endothelial cells (muLECs), embedded in the leptomeninges, form an immune niche surrounding the brain that contributes to brain immunosurveillance. Here, we report that the brain controls the development of muLECs via a specialized glial subpopulation, slc6a11b+ radial astrocytes (RAs), a process modulated by neural activity in zebrafish. slc6a11b+ RAs, with processes extending to the meninges, govern muLEC formation by expressing vascular endothelial growth factor C (vegfc). Moreover, neural activity regulates muLEC development, and this regulation requires Vegfc in slc6a11b+ RAs. Intriguingly, slc6a11b+ RAs cooperate with calcium-binding EGF domain 1 (ccbe1)+ fibroblasts to restrict muLEC growth on the brain surface via controlling mature Vegfc distribution. Thus, our study uncovers a glia-mediated and neural-activity-regulated control of brain lymphatic development and highlights the importance of inter-tissue cellular cooperation in development. © 2025 Elsevier Inc.

关键词： development fibroblast immune system leptomeninges meningeal mural lymphatic endothelial cells nervous system neural activity radial astrocyte VEGFC

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Research on Reliability Assessment Method of Emergency Escape Parachute

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Journal of Physics: Conference Series 2020年第1期1544卷

作者： Fangyun Ma Huajin Lei Wensheng Wang Jing Liu Liying Jin Aviation Key Laboratory Science and Technology on Life-Support Technology Hubei Xiangyang 441003 China Aerospace Life-Support Industries Ltd. Hubei Xiangyang 441003 China School of Mechanical Engineering Hubei University of Arts and Science Xiangyang 441053 China

Aiming at the problem that emergency escape parachute cannot meet the requirements of the index using the binomial evaluation method, combined with the characteristics of emergency escape parachute products, comprehensively using emergency escape parachute components and system test data, the emergency escape parachute Bayesian reliability assessment method is proposed to solve the problem of reliability assessment in the case of small sample size of emergency escape parachute system test, which effectively reducing emergency escape parachute test expenses and development cycle.

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