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| 1 | Age-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 | 2020 | Animal Models and Experimental Medicine2020，3，1： | 22 |
| 2 | Sequential 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 | 2021 | Signal Transduction and Targeted Therapy2021，6，6： | 4 |
| 3 | Sensitivity of SARS-CoV-2 to different temperatures显示文摘This study was designed to investigate the sensitivity of SARS-CoV-2 to different temperatures,to provide basic data and a scientific basis for the control of COVID-19 epidemic.The virus was dispersed in 1 mL basal DMEM medium at a final concentration of 103.2 TCID 50/mL and then incubated at 4,22,30,35,37,38,39 and 40°C for up to 5 days.The infectivity of residual virus was titrated using the Vero E6 cell line.The results showed that the virus remained viable for 5 days at 4°C,and for 1 day only at 22 and 30°C.We found that the infectivity of the virus was completely lost after less than 12 hours at 37,38 and 39°C,while at 40°C,the inactivation time of the virus was rapidly reduced to 6 hours.We show that SARS-CoV-2 is sensitive to heat,is more stable at lower temperatures than higher temperature,remains viable for longer at lower temperatures,and loses viability rapidly at higher temperatures. | Qi Lv Mingya Liu Feifei Qi Shuran Gong Shasha Zhou Shisheng Zhan Linlin Bao | 2020 | Animal Models and Experimental Medicine2020，3，4： | 3 |
| 4 | Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients显示文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many countries.However,the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown.Here,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune systems.The viral protein partially co-localized with activated Mac-2+macrophages throughout the body.Moreover,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal COVID-19.Particularly,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune dysregulation.Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation.Melatonin,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted medicine.Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers. | Zhiqi Song Linlin Bao Wei Deng Jiangning Liu Erjun Ren Qi Lv Mingya Liu Feifei Qi Ting Chen Ran Deng Fengdi Li Yunpeng Liu Qiang Wei Hong Gao Pin Yu Yunlin Han Wenjie Zhao Junjun Zheng Xujian Liang Fuhe Yang Chuan Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 2 |
| 5 | Sequential immunizations confer cross-protection against variants of SARS-CoV-2,including Omicron in Rhesus macaques显示文摘Variants of concern(VOCs)like Delta and Omicron,harbor a high number of mutations,which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies(NAbs).In this study,Rhesus macaques immunized with 2-dose inactivated vaccines(Coronavac)were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine,or a bivalent inactivated vaccine(Beta and Delta)to determine the effectiveness of sequential immunization.The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type. | Wei Deng Qi Lv Fengdi Li Jiangning Liu Zhiqi Song Feifei Qi Qiang Wei Pin Yu Mingya Liu Shasha Zhou Yaqing Zhang Hong Gao Nan Wang Zijing Jia Kai Gao Jiayi Liu Chong Xiao Haiquan Shang Xiangxi Wang Linlin Bao Chuan Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 2 |
| 6 | Microstructure and properties of Bi-2223/Ag/Ni tapes显示文摘To reduce the production cost of Bi-2223 superconducting tapes, Bi-2223/Ag/Ni tapes were fabricated by the powder-in-tube process. The effect of heat treatment on the microstructure and critical current of the Bi-2223/Ag/Ni tapes were studied. The phase compositions of the samples were characterized using XRD. The microstructure was observed using SEM. Experimental results indicate that higher temperature is more conducive to the formation of Bi-2223 phase at an atmosphere of 8.5% O 2 . After the two-step heat treatment, the critical current of samples is about 67.5 A. | Li Mingya Ye Chengli Liu Jun | 2012 | Rare Metals2012，31，6： | 2 |
| 7 | Sequentially immune-induced antibodies could cross-neutralize SARS-CoV-2 variants显示文摘Background:The Omicron(B.1.1.529)SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike protein.Since the vaccine-induced neutralizing antibody targets are the spike protein,this may lead to the possibility of vaccine-induced hu-moral immunity escape.Methods:We measured the neutralizing activity in vitro for Omicron and compared this with wild type(WH-09)and Delta variants in human and monkey sera from different types of immunity.The monkey sera samples were collected at 1 and 3 months post three-dose inactivated(PiCoVacc)and recombinant protein(ZF2001)vaccination.Human sera were collected from 1 month post three-dose inactivated vaccination.Results:In inactivated vaccine sera,at 1/3 months post three-dose,geometric mean titers(GMTs)of neutralization antibody(NAb)against the Omicron variant were 4.9/5.2-fold lower than those of the wild type.In recombinant protein vaccine sera,GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild type.In human sera,at 1 month post three-dose inactivated vaccination,GMTs of NAb against Omicron were 3.1-fold lower than those of the wild type.Conclusion:This study demonstrated that despite a reduction in neutralization titers,cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination. | Qi Lv Shasha Zhou Feifei Qi Yaqing Zhang Fengdi Li Mingya Liu Linlin Bao | 2022 | Animal Models and Experimental Medicine2022，5，1： | 1 |
| 8 | Diverse O-methyltransferases catalyze the biosynthesis of floral benzenoids that repel aphids from the flowers of waterlily Nymphaea prolifera显示文摘Nymphaea is a key genus of the ANA grade(Amborellales,Nymphaeales,and Austrobaileyales)of basal flowering plants,which serve as a key model to study the early evolution of floral traits.In this study,we comprehensively investigated the emission,biosynthesis,and biological function of the floral scent in a night-blossoming waterlily Nymphaea prolifera.The headspace volatile collection combined with GC-MS analysis showed that the floral scent of N.prolifera is predominately comprised by methylated benzenoids including anisole,veratrole,guaiacol,and methoxyanisole.Moreover,the emission of these floral benzenoids in N.prolifera exhibited temporal and spatial pattern with circadian rhythm and tissue specificity.By creating and mining transcriptomes of N.prolifera flowers,12 oxygen methyltransferases(NpOMTs)were functionally identified.By in vitro enzymatic assay,NpOMT3,6,and 7 could produce anisole and NpOMT5,7,9,produce guaiacol,whereas NpOMT3,6,9,11 catalyzed the formation of veratrole.Methoxyanisole was identified as the universal product of all NpOMTs.Expression patterns of NpOMTs provided implication for their roles in the production of the respective benzenoids.Phylogenetic analysis of OMTs suggested a Nymphaea-specific expansion of the OMT family,indicating the evolution of lineage-specific functions.In bioassays,anisole,veratrole,and guaiacol in the floral benzenoids were revealed to play the critical role in repelling waterlily aphids.Overall,this study indicates that the basal flowering plant N.prolifera has evolved a diversity and complexity of OMT genes for the biosynthesis of methylated benzenoids that can repel insects from feeding the flowers.These findings provide new insights into the evolutional mechanism and ecological significance of the floral scent from early-diverged flowering plants. | Guanhua Liu Jianyu Fu Lingyun Wang Mingya Fang Wanbo Zhang Mei Yang Xuemin Yang Yingchun Xu Lin Shi Xiaoying Ma Qian Wang Hui Chen Cuiwei Yu Dongbei Yu Feng Chen Yifan Jiang | 2023 | Horticulture Research2023，10，12： | 0 |
| 9 | Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro显示文摘Background:New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and BA.5.Their pathogenicity has changed from that of wild-type(WH-09)and Omicron variants have over time become globally dominant.The spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants,which is likely to cause immune es-cape and the reduction of the protective effect of the vaccine.Our study addresses the above issues and provides a basis for formulating relevant prevention and control strategies.Methods:We collected cellular supernatant and cell lysates and measured the viral titers,viral RNA loads,and E subgenomic RNA(E sgRNA)loads in different Omicron subvariants grown in Vero E6 cells,using WH-09 and Delta variants as a reference.Additionally,we evaluated the in vitro neutralizing activity of different Omicron sub-variants and compared it to the WH-09 and Delta variants using macaque sera with different types of immunity.Results:As the SARS-CoV-2 evolved into Omicron BA.1,the replication ability in vitro began to decrease.Then with the emergence of new subvariants,the replication ability gradually recovered and became stable in the BA.4 and BA.5 subvariants.In WH-09-inactivated vaccine sera,geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.7~15.4-fold compared to those against WH-09.In Delta-inactivated vaccine sera,geometric mean titers of neutrali-zation antibodies against Omicron subvariants declined by 3.1~7.4-fold compared to those against Delta.Conclusion:According to the findings of this research,the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants,and was lower in BA.1 than in other Omicron subvariants.After two doses of inactivated(WH-09 or Delta)vaccine,cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers. | Yaqing Zhang Qi Lv Feifei Qi Fengdi Li Ran Deng Xujian Liang Mingya Liu Yiwei Yan Linlin Bao | 2023 | Animal Models and Experimental Medicine2023，6，1： | 0 |
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