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1Age-related rhesus macaque models of COVID-19显示文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song Yajin Qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin 2020Animal Models and Experimental Medicine2020,3,1:22
2Self-Powered Implantable Skin-Like Glucometer for Real-Time Detection of Blood Glucose Level In Vivo显示文摘Implantable bioelectronics for analyzing physiological biomarkers has recently been recognized as a promising technique in medical treatment or diagnostics. In this study, we developed a self-powered implantable skinlike glucometer for real-time detection of blood glucose level in vivo. Based on the piezo-enzymatic-reaction coupling effect of GOx@ZnO nanowire, the device under an applied deformation can actively output piezoelectric signal containing the glucose-detecting information. No external electricity power source or battery is needed for this device, and the outputting piezoelectric voltage acts as both the biosensing signal and electricity power. A practical application of the skin-like glucometer implanted in mouse body for detecting blood glucose level has been simply demonstrated. These results provide a new technique path for diabetes prophylaxis and treatment.Wanglinhan Zhang Linlin Zhang Huiling Gao Wenyan Yang Shuai Wang Lili Xing Xinyu Xue 2018Nano-Micro Letters2018,10,2:9
3World’s first spaceflight on-orbit demonstration of a flexible solar array system based on shape memory polymer composites显示文摘With a 10%reversible compressive strain in more than 10 deformation cycles,the shape memory polymer composites(SMPCs)could be used for deployable structure and releasing mechanism.In this paper,without traditional electro-explosive devices or motors/controllers,the deployable SMPC flexible solar array system(SMPC-FSAS)is studied,developed,ground-based tested,and finally on-orbit validated.The epoxy-based SMPC is used for the rolling-out variable-stiffness beams as a structural frame as well as an actuator for the flexible blanket solar array.The releasing mechanism is primarily made of the cyanate-based SMPC,which has a high locking stiffness to withstand 50 g gravitational acceleration and a large unlocking displacement of 10 mm.The systematical mechanical and thermal qualification tests of the SMPC-FSAS flight hardware were performed,including sinusoidal sweeping vibration,shocking,acceleration,thermal equilibrium,thermal vacuum cycling,and thermal cycling test.The locking function of the SMPC releasing mechanisms was in normal when launching aboard the SJ20 Geostationary Satellite on 27 Dec.,2019.The SMPC-FSAS flight hardware successfully unlocked and deployed on 5 Jan.,2020 on geostationary orbit.The triggering signal of limit switches returned to ground at the 139 s upon heating,which indicated the successful unlocking function of SMPC releasing mechanisms.A pair of epoxy-based SMPC rolled variable-stiffness tubes,which clapped the flexible blanket solar array,slowly deployed and finally approached an approximate 100%shape recovery ratio within 60 s upon heating.The study and on-orbit successful validation of the SMPC-FSAS flight hardware could accelerate the related study and associated productions to be used for the next-generation releasing mechanisms as well as space deployable structures,such as new releasing mechanisms with low-shocking,testability and reusability,and ultra-large space deployable solar arrays.LAN Xin LIU LiWu ZHANG FengHua LIU ZhengXian WANG LinLin LI QiFeng PENG Fan HAO SiDa DAI WenXu WAN Xue TANG Yong WANG Mian HAO YanYan YANG Yang YANG Cheng LIU YanJu LENG JinSong 2020Science China(Technological Sciences)2020,63,8:7
4Sequential infection with H1N1 and SARS-CoV-2 aggravated COVID-19 pathogenesis in a mammalian model, and covaccination as an effective method of prevention of COVID-19 and influenza显示文摘Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus,leading to more serious respiratory diseases during this winter.However,the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear.Using a mammalian model,sequential infection was performed in ferrets and in K18-MCE2 mice,with SARS-CoV-2 infection following H1N1.We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19,and enhanced pulmonary damage,but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets.Moreover,mortality was increased in sequentially infected mice compared with single-infection mice.Compared with singlevaccine inoculation,co-inoculation of PiCoVacc(a SARS-CoV-2 vaccine)and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses.Combined immunization effectively protected K18-MCE2 mice against both H1N1 and SARS-CoV-2 infection.Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2,which together notably enhanced pneumonia in ferrets and mice,as well as demonstrated that simultaneous vaccination against HINT and SARS-CoV-2 may be an effective prevention strategy for the coming winter.Linlin Bao Wei Deng Feifei Qi Qi Lv Zhiqi Song Jiangning Liu Hong Gao Qiang Wei Pin Yu Yanfeng Xu Yajin Qu Fengdi Li Jing Xue Shuran Gong Mingya Liu Guanpeng Wang Shunyi Wang Binbin Zhao Bin Cong Chuan Qin 2021Signal Transduction and Targeted Therapy2021,6,6:4
5SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice显示文摘Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.Yuanwu Ma Dan Lu Linlin Bao Yajin Qu Jiangning Liu Xiaolong Qi Lei Yu Xu Zhang Feifei Qi Qi Lv Yunpeng Liu Xudong Shi Caixian Sun Jing Li Jie Wang Yunlin Han Kai Gao Wei Dong Ning Liu Shan Gao Jing Xue Qiang Wei Sidan Pan Hong Gao Lianfeng Zhang Chuan Qin 2021Animal Models and Experimental Medicine2021,4,1:3
6Co-expression Analysis Identifies CRC and AP1 the Regulator of Arabidopsis Fatty Acid Biosynthesis显示文摘Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as 'guide genes' to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis.Xinxin Han Linlin Yin Hongwei Xue 2012Journal of Integrative Plant Biology2012,54,7:3
7Synthesis and antiviral activity of some novel indole-2-carboxylate derivatives显示文摘A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity.Notably,compound 8f showed the highest SI value(17.1)to Cox B3 virus.Compound 14f showed both potent inhibitory activity against influenza A(IC_(50)=7.53μmol/L)and the highest SI value(12.1).SAR results showed that the alkyloxy at the 4-position of indole ring was not crucial to the antiviral activities.Incorporation of an acetyl substituent at the amino group disfavored antiviral activity towards RNA viruses.Situ Xue Linlin Ma Rongmei Gao Yuhuan Li Zhuorong Li 2014Acta Pharmaceutica Sinica B2014,4,4:3
8SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration显示文摘SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals.However,it remains undear whether and how SARS-CoV-2 crosses the blood-brain barrier(BBB).Herein,SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space,as well as in brain microvascular endothelial cells(BMECs)in the infected K18-hACE2 transgenic mice.Moreover,the permeability of the infected vessel was in creased.Furthermore,disin tegrity of BBB was discovered in the infected hamsters by administration of Evans blue.Interestingly,the expression of claudin5,ZO-1,occludin and the ultrastructure of tight junctions(TJs)showed unchanged,whereas,the basement membrane was disrupted in the infected animals.Using an in vitro BBB model that comprises primary BMECs with astrocytes,SARS-CoV-2 was found to infect and cross through the BMECs.Consistent with in vivo experiments,the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs.Besides,inflammatory responses including vasculitis,glial activation,and upregulated inflammatory factors occurred after SARS-CoV-2 infection.Overall,our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.Ling Zhang Li Zhou Linlin Bao Jiangning Liu Hua Zhu Qi Lv Ruixue Liu Wei Chen Wei Tong Qiang Wei Yanfeng Xu Wei Deng-Hong Gao Jing Xue Zhiqi Song Pin Yu Yunlin Han Yu Zhang Xiuping Sun Xuan Yu Chuan Qin 2021Signal Transduction and Targeted Therapy2021,6,10:2
9Isolation and genetic analysis revealed no predominant new strains of avian infectious bronchitis virus circulating in South China during 2004–2008显示文摘Linlin Li Chunyi Xue Feng Chen Jianping Qin Qingmei Xie Yingzuo Bi Yongchang Cao 2009Veterinary Microbiology2009,,2:2
10Effects of a combination of Japanese Raisin Tree Seed and Flower of Lobed Kudzuvine against acute alcohol-induced liver injury in mice显示文摘Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods:Male ICR mice were randomly allocated to six groups:a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination(at a ratio of 2:1).Animals were orally administered 56%alcohol(Er Guo-tou white spirit,0.12 mL/10 g/d)for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and western blotting.Results:Compared with the model group,GH-ZJZ(2:1)had lower serum ALT(12.15±0.39,P紏.003),AST(104.07±1.03,P紏.001),and ALP(148.09±2.55,P紏.010)activities,and lower TC(1.97±0.05,P紏.001)and TG(1.54±0.07,P?.002)concentrations.GH-ZJZ(2:1)also significantly increased the hepatic activities of SOD and GSH(4.24±0.25 and 1.57±0.06,respectively;both P<.01),reduced the ROS and MDA concentrations(97.50±3.00 and 2.39±0.19,respectively;both P<.01),and upregulated Nrf2 expression(P<.01).GH-ZJZ(2:1)significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice(P<.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion:We have demonstrated protective effects of GH-ZJZ(2:1)against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.Wan Xu Shaohong Chen Gansheng Zhong Haiyan Liu Linlin Xiu Xue Yu Feng Chen Na Li Yanmin Lv 2020Journal of Traditional Chinese Medical Sciences2020,7,1:2
11Therapeutic efficacy of Pudilan Xiaoyan Oral Liquid(PDL)for COVID-19 in vitro and in vivo显示文摘Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed cases.Until now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 infection.Existing medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection.Wei Deng Yanfeng Xu Qi Kong Jing Xue Pin Yu Jiangning Liu Qi Lv Fengdi Li Qiang Wei Linlin Bao 2020Signal Transduction and Targeted Therapy2020,5,1:2
12Polymorphism study of seven SNPs at ADH genes in 15 Chinese populations Heieditas显示文摘LINLIN M A YALI XUE YAN LIU 2005142:103-1112005,142,:1
13Studies of the impedance models and water transport behaviors of cathodically polarized coating显示文摘Chengfei Zhu Rui Xie Jinhua Xue Linlin Song 2011Electrochimica Acta2011,,16:1
14Proteomic analysis of purified coronavirus infectious bronchitis virus particles显示文摘KONG Qingming XUE Chunyi REN Xiangpeng ZHANG Chengwen LI Linlin SHU Dingming BI Yingzuo CAO Yongchang 2010Proteome Science2010,8,:1
15Stretchable graded multichannel self-powered respiratory sensor inspired by shark gill显示文摘Respiratory sensing provides a simple,non-invasive,and efficient way for medical diagnosis and health monitoring,but it relies on sensors that are conformal,accurate,durable,and sustainable working.Here,a stretchgll structure can convert transverse elastic deformation into longitudinal elastic deformation during stretching.able,multichannel respiratory sensor inspired by the structure of shark gill cleftis reported.The bionic shark Combining the optimized bionic shark gll structure with the piezoelectric and the triboelectric effect,the bionic shark gill respiratory sensor(BSG-RS)can produce a graded electrical response to different tensile strains.Based on this feature,BSG-RS can simultaneously monitor the breathing rate and breathing depth of the human body accurately,and realize the effective recognition of the different human body's breathing state under the supporting software,With good stretchability,wearabilit,acuracy,and long-term stability(50,0oo cycles),BSG-RS is expected to be applied as self-powered smart wearables for mobile medical diagnostic analysis in the future.Yang Zou Yansong Gai Puchuan Tan Dongjie Jiang Xuecheng Qu Jiangtao Xue Han Ouyang Bojing Shi Linlin Li Dan Luo Yulin Deng Zhou Li Zhong Lin Wang 2022Fundamental Research2022,2,4:1
16Coupled-mode a- nalysis for chiral fiber long-period gratings using local mode approach 显示文摘Jingren Qian Jue Su Linlin Xue 2012IEEE Journal of Quantum Electron- ics2012,48,1:1
17Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71显示文摘Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to death.Currently,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are available.Here,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in cells.The cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of VP1.In a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic treatment.In particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment.Zhe Chen Linlin Bao Bin Zhu Hua Fu Shuangli Zhu Tianjiao Ji Ying Xue Chuan Liu Xurong Wang Fengdi Li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo Xu Chuan Qin Hongrong Liu Qi Jin 2022Science China(Life Sciences)2022,65,12:0
18NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice显示文摘Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease,but the role of natriuretic peptide receptor C(NPRC)in the pathogenesis of atherosclerosis(AS)remains unknown.This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress,inflammation,and apoptosis via protein kinase A(PKA)signaling.ApoE^(−/−)mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice.Systemic NPRC knockout mice were crossed with ApoE^(−/−)mice to generate ApoE^(−/−)NPRC^(−/−)mice,and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE^(−/−)NPRC^(−/−)versus ApoE^(−/−)mice.In addition,endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice.In contrast,endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice.Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells(HAECs)inhibited ROS production,pro-inflammatory cytokine expression and endothelial cell apoptosis,and increased eNOS expression.Furthermore,NPRC knockdown in HAECs suppressed macrophage migration,cytokine expression,and phagocytosis via its effects on endothelial cells.On the contrary,NPRC overexpression in endothelial cells resulted in opposite effects.Mechanistically,the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway,leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway.In conclusion,NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE^(−/−)mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways.Thus,targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.Cheng Cheng Jie Zhang Xiaodong Li Fei Xue Lei Cao Linlin Meng Wenhai Sui Meng Zhang Yuxia Zhao Bo Xi Xiao Yu Feng Xu Jianmin Yang Yun Zhang Cheng Zhang 2023Signal Transduction and Targeted Therapy2023,8,9:0
19Optimization method for a radar situation interface from error-cognition to information feature mapping显示文摘With the rapid development of digital and intelligent information systems, display of radar situation interface has become an important challenge in the field of human-computer interaction. We propose a method for the optimization of radar situation interface from error-cognition through the mapping of information characteristics. A mapping method of matrix description is adopted to analyze the association properties between error-cognition sets and design information sets. Based on the mapping relationship between the domain of error-cognition and the domain of design information, a cross-correlational analysis is carried out between error-cognition and design information.We obtain the relationship matrix between the error-cognition of correlation between design information and the degree of importance among design information. Taking the task interface of a warfare navigation display as an example, error factors and the features of design information are extracted. Based on the results, we also propose an optimization design scheme for the radar situation interface.WU Xiaoli WEI Wentao CALDWELL Sabrina XUE Chengqi WANG Linlin 2022Journal of Systems Engineering and Electronics2022,33,4:0
20Theoretical Calculations of the pKa Values of 1-Aryl-4-prooylpiperazine Drugs in Aqueous Solution显示文摘FAN Linlin YANG Xin TIAN Zhiyue ZHAO Xuekun LI Ruixiang XUE Ying 2014Chemical Research in Chinese Universities2014,30,3:0
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