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| 1 | Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China显示文摘To control the spread of the 2019 novel coronavirus(COVID-19),China imposed nationwide restrictions on the movement of its population(lockdown)after the Chinese New Year of 2020,leading to large reductions in economic activities and associated emissions.Despite such large decreases in primary pollution,there were nonetheless several periods of heavy haze pollution in eastern China,raising questions about the well-established relationship between human activities and air quality.Here,using comprehensive measurements and modeling,we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution.In particular,large decreases in NOx emissions from transportation increased ozone and nighttime NO_(3)radical formation,and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter.Our results,afforded by the tragic natural experiment of the COVID-19 pandemic,indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants. | Xin Huang Aijun Ding Jian Gao Bo Zheng Derong Zhou Ximeng Qi Rong Tang Jiaping Wang Chuanhua Ren Wei Nie Xuguang Chi Zheng Xu Liangduo Chen Yuanyuan Li Fei Che Nini Pang Haikun Wang Dan Tong Wei Qin Wei Cheng Weijing Liu Qingyan Fu Baoxian Liu Fahe Chai Steven JDavis Qiang Zhang Kebin He | 2021 | National Science Review2021,8,2: | 47 |
| 2 | Analysis and Numerical Simulation of Rolling Contact between Sphere and Cone显示文摘In non-conforming rolling contact, the contact stress is highly concentrated in the contact area. However, there are some limitations of the special contact model and stress model used for the theoretical study of the phenomenon, and this has prevented in-depth analysis of the associated friction, wear, and failure. This paper is particularly aimed at investigating the area of rolling contact between a sphere and a cone, for which purpose the boundary is determined by the Hertz theory and the geometries of the non-conforming surfaces. The phenomenon of stick-slip contact is observed to occur in the contact area under the condition of no-full-slip(Q < μ·P). Using the two-dimensional rolling contact theory developed by CARTER, the relative positions of the stick and slip regions and the distribution of the tangential force over the contact area are analyzed. Furthermore, each stress component is calculated based on the Mc Ewen theory and the idea of narrow band. The stress equations for the three-dimensional rolling contact between the sphere and the cone are obtained by the principle of superposition, and are used to perform some numerical simulations. The results show that the stress components have a large gradient along the boundary between the stick and slip regions, and that the maximum stress is inversely proportional to the contact coefficient and proportional to the friction coefficient. A new method for investigating the stress during non-classical three-dimensional rolling contact is proposed as a theoretical foundation for the analysis of the associated friction, wear, and failure. | ZHAO Yanling XIA Chengtao WANG Hongbo XUAN Jiaping XIANG Jingzhong LIU Xianli SU Xiangguo | 2015 | Chinese Journal of Mechanical Engineering2015,28,3: | 18 |
| 3 | Evaluation Method and Mitigation Strategies for Shrinkage Cracking of Modern Concrete显示文摘The complex compositions and large shrinkage of concrete,as well as the strong constraints of the structures,often lead to prominent shrinkage cracking problems in modem concrete structures.This paper first introduces a multi-field(hydro-thermo-hygro-constraint)coupling model with the hydration degree of cementitious materials as the basic state parameter to estimate the shrinkage cracking risk of hardening concrete under coupling effects.Second,three new key technologies are illustrated:temperature rise inhibition,full-stage shrinkage compensation,and shrinkage reduction technologies.These technologies can efficiently reduce the thermal,autogenous,and drying shrinkages of concrete.There after,a design process based on the theoretical model and key technologies is proposed to control thecracking risk index below the threshold value.Finally,two engineering application examples are provided that demonstrate that concrete shrinkage cracking can be significantly mitigated by adopting the proposed methods and technologies. | Jiaping Liu Qian Tian Yujiang Wang Hua Li Wen Xu | 2021 | Engineering2021,7,3: | 15 |
| 4 | Chinese kangs and building energy consumption显示文摘Chinese kangs are an integrated system for cooking, sleeping and heating in rural Northern China with more than 2000 years history. In 2004 there were 67 million Chinese kangs used by 44 million rural families or 174 million people. Chinese kangs store surplus heat from stove during cooking and re-leases it later for both home heating and localized bed heating. Such a widely used heating system has been rarely studied. Understanding kangs is important for developing new effective home heating systems for better energy efficiency and improving indoor air quality in Northern China. In this paper, we review and present some preliminary results from our field measurement and mathematical mod-eling, and discuss the development of Chinese kangs as related to future energy consumption in rural homes, and building energy consumption in China in general. We suggest that transition and new technologies for rural home heating in Northern China, i.e. the future of Chinese kangs, should be considered as the top priority in managing future building energy consumption in China. | LI YuGuo ZHUANG Zhi LIU JiaPing | 2009 | Chinese Science Bulletin2009,54,6: | 11 |
| 5 | Comparison of survival outcomes between transthoracic and transabdominal surgical approaches in patients with Siewert-Ⅱ/Ⅲesophagogastric junction adenocarcinoma:a single-institution retrospective cohort study显示文摘Objective: To compare the survival outcomes of transabdominal(TA) and transthoracic(TT) surgical approaches in patients with Siewert-Ⅱ/Ⅲ esophagogastric junction adenocarcinoma.Methods: This retrospective study was conducted in patients with Siewert-Ⅱ/Ⅲ esophagogastric junction adenocarcinoma who underwent either TT or TA operations in the West China Hospital between January 2006 and December 2009.Results: A total of 308 patients(109 in the TT and 199 in the TA groups) were included in this study with a follow-up rate of 87.3%. The median(P25, P75) number of harvested perigastric lymph nodes was 8(5, 10) in the TT group and 23(16, 34) in the TA group(P<0.001), and the number of positive perigastric lymph nodes was 2(0, 5) in the TT group and 3(1, 8) in the TA group(P<0.004). The 5-year overall survival(OS) rate was 36% in the TT group and 51% in the TA group(P=0.005). Subgroup analysis by Siewert classification showed that 5-year OS rates for patients with Siewert Ⅱ tumors were 38% and 48% in TT and TA groups, respectively(P=0.134), whereas the 5-year OS rate for patients with Siewert Ⅲ tumors was significantly lower in the TT group than that in the TA group(33% vs. 53%; P=0.010). Multivariate analysis indicated that N2 and N3 stages, R1/R2 resection and a TT surgical approach were prognostic factors for poor OS.Conclusions: Improved perigastric lymph node dissection may be the main reason for better survival outcomes observed with a TA gastrectomy approach than with TT gastrectomy for Siewert Ⅲ tumor patients. | Weihan Zhang Xinzu Chen Kai Liu Kun Yang Xiaolong Chen Ying Zhao Yongfan Zhao Jiaping Chen Longqi Chen Jiankun Hu | 2016 | Chinese Journal of Cancer Research2016,28,4: | 10 |
| 6 | Advances in ultra-high temperature ceramics,composites,and coatings显示文摘Ultra-high temperature ceramics(UHTCs)are generally referred to the carbides,nitrides,and borides of the transition metals,with the Group IVB compounds(Zr&Hf)and TaC as the main focus.The UHTCs are endowed with ultra-high melting points,excellent mechanical properties,and ablation resistance at elevated temperatures.These unique combinations of properties make them promising materials for extremely environmental structural applications in rocket and hypersonic vehicles,particularly nozzles,leading edges,and engine components,etc.In addition to bulk UHTCs,UHTC coatings and fiber reinforced UHTC composites are extensively developed and applied to avoid the intrinsic brittleness and poor thermal shock resistance of bulk ceramics.Recently,high-entropy UHTCs are developed rapidly and attract a lot of attention as an emerging direction for ultra-high temperature materials.This review presents the state of the art of processing approaches,microstructure design and properties of UHTCs from bulk materials to composites and coatings,as well as the future directions. | Dewei NI Yuan CHENG Jiaping ZHANG Ji-Xuan LIU Ji ZOU Bowen CHEN Haoyang WU Hejun LI Shaoming DONG Jiecai HAN Xinghong ZHANG Qiangang FU Guo-Jun ZHANG | 2022 | Journal of Advanced Ceramics2022,11,1: | 9 |
| 7 | Precautionary Saving and Health Insurance: A Portfolio Choice Perspective显示文摘这份报纸在家庭公事包选择上分析健康保险的影响。用消费者金融和健康退休调查数据库的美国调查,它发现保证家庭对自己的股票更可能并且比未保过险的家庭有货投资金融财产的一个更大的比例。结果甚至在为家庭特征和反向的诱发性控制以后仍然保持强壮。进一步,结果越过不同调查年和数据来源是柔韧的。它建议那一预防动机在家庭公事包选择决定是强壮的。 | Jiaping Qiu | 2016 | Frontiers of Economics in China-Selected Publications from Chinese Universities2016,11,2: | 9 |
| 8 | Genetic Polymorphisms in the Precursor MicroRNA Flanking Region and Non-Small Cell Lung Cancer Survival显示文摘 | Hu, Zhibin Shu, Yongqian Chen, Yijiang Chen, Jiaping Dong, Jing Liu, Yao Pan, Shiyang Xu, Lin Xu, Jing Wang, Yi Dai , Juncheng Ma, Hongxia Jin, Guangfu Shen,Hongbing | 2011 | 南京医科大学学报(自然科学版)2011,31,6: | 8 |
| 9 | Genetic variants in RAN, DICER and HIWI of microRNA biogenesis genes and risk of cervical carcinoma in a Chinese population显示文摘Objective:Recent evidence indicates that dysregulation of microRNA(miRNA)biogenesis is implicated in cancer development and progression.Based on the important role of miRNA biogenesis genes in carcinogenesis,we hypothesized that genetic variations of the miRNA biogenesis genes may modulate susceptibility to cervical cancer.Methods:We identified three single nucleotide polymorphisms(SNPs)located in the 3'-untranslated regions(3'-UTR)of of miRNA biogenesis key genes(rs1057035 in DICER,rs3803012 in RAN and rs10773771 in HIWI)and genotyped these SNPs in a case-control study of 1,486 cervical cancer cases and1,549 cancer-free controls in Chinese women.Results:Logistic regression analyses showed that no significant associations were observed between the three SNPs and cervical cancer risk[rs3803012 in RAN AG/GG vs.AA adjusted OR=1.104,95%confidence interval(CI):0.859-1.419;rs1057035 in DICER CT/CC vs.TT adjusted OR=0.962,95%CI:0.805-1.149;rs10773771 in HIWI CT/CC vs.TT adjusted OR=0.963,95%CI:0.826-1.122].Conclusions:The findings did not suggest that genetic variants in the 3'-UTR of RAN,DICER and HIWI of miRNA biogenesis genes were associated with the risk of cervical cancer in this Chinese population. | Jiaping Chen Zhenzhen Qin Shandong Pan Jie Jiang Li Liu Jibin Liu Xiaojun Chen Zhibin Hu Hongbing Shen | 2013 | Chinese Journal of Cancer Research2013,25,5: | 8 |
| 10 | Dynamic response of concrete pavement structure with asphalt isolating layer under moving loads显示文摘A three-dimensional finite element model(3D FEM) is built using ABAQUS to analyze the dynamic response of a concrete pavement structure with an asphalt isolating layer under moving loads.The 3D model is prepared and validated in the state of no asphalt isolating layer.Stress and deflection at the critical load position are calculated by changing thickness,modulus of isolating layer and the combination between the isolating layer and concrete slab.Analysis result shows that the stress and deflection of the concrete slab increase with the increase of thickness.The stress and deflection of the concrete slab decrease with the increase of combination between the isolating layer and concrete slab.The influence of changing the isolating layer modulus to the stress and deflection of the concrete slab is not significant.From the results,asphalt isolating layer design is suggested in concrete pavement. | Jianmin Wu Jiaping Liang Sanjeev Adhikari | 2014 | Journal of Traffic and Transportation Engineering(English Edition)2014,1,6: | 7 |
| 11 | Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors显示文摘Programmed cell death protein-1(PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T(CAR-T)cells in solid tumors.We generated PD-1 and T cell receptor(TCR)deficient mesothelin-specific CAR-T(MPTK-CAR-T)cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study.A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion.No dose-limiting toxicity or unexpected adverse events were observed in any of the 15 patients.The best overall response was stable disease(2/15 patients).Circulating MPTK-CAR-T cells peaked at days 7–14 and became undetectable beyond 1 month.TCR-positive CAR-T cells rather than TCR-negative CAR-T cells were predominantly detected in effusion or peripheral blood from three patients after infusion.We further confirmed the reduced persistence of TCR-deficient CAR-T cells in animal models.Our results establish the preliminary feasibility and safety of CRISPR-engineered CAR-T cells with PD-1 disruption and suggest that the natural TCR plays an important role in the persistence of CAR-T cells when treating solid tumors. | Zhenguang Wang Na Li Kaichao Feng Meixia Chen Yan Zhang Yang Liu Qingming Yang Jing Nie Na Tang Xingying Zhang Chen Cheng Lianjun Shen Jiaping He Xun Ye Wei Cao Haoyi Wang Weidong Han | 2021 | Cellular & Molecular Immunology2021,18,9: | 7 |
| 12 | Micro/nano multiscale reinforcing strategies toward extreme high-temperature applications:Take carbon/carbon composites and their coatings as the examples显示文摘Carbon fiber reinforced carbon composites(C/Cs),are the most promising high-temperature materials and could be widely applied in aerospace and nucleation fields,owing to their superior performances.However,C/Cs are very susceptible to destructive oxidation and thus fail at elevated temperatures.Though matrix modification and coating technologies with Si-based and ultra-high temperature ceramics(UHTCs)are valid to enhance the oxidation/ablation resistance of C/Cs,it’s not sufficient to satisfy the increasing practical applications,due to the inherent brittleness of ceramics,mismatch issues between coatings and C/C substrates,and the fact that carbonaceous matrices are easily prone to high-temperature oxidation.To effectively solve the aforementioned problems,micro/nano multiscale reinforcing strategies have been developed for C/Cs and/or the coatings over the past two decades,to fabricate C/Cs with high strength and excellent high-temperature stability.This review is to systematically summarize the most recent major and important advancements in some micro/nano multiscale strategies,including nanoparticles,nanowires,carbon nanotubes/fibers,whiskers,graphene,ceramic fibers and hybrid micro/nano structures,for C/Cs and/or the coatings,to achieve high-temperature oxidation/ablation-resistant C/Cs.Finally,this review is concluded with an outlook of major unsolved problems,challenges to be met and future research advice for C/Cs with excellent comprehensive mechanical-thermal performance.It’s hoped that a better understanding of this review will be of high scientific and industrial interest,since it provides unusual and feasible new ideas to develop potential and practical C/Cs with improved high-temperature mechanical and oxidation/ablation-resistant properties. | Qiangang Fu Pei Zhang Lei Zhuang Lei Zhou Jiaping Zhang Jie Wang Xianghui Hou Ralf Riedel Hejun Li | 2022 | Journal of Materials Science & Technology2022,,1: | 7 |
| 13 | Prognostic assessment of apoptotic gene polymorphisms in non-small cell lung cancer in Chinese显示文摘Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypothesis, we selected 38 potentially functional single nucleotide polymorphisms (SNPs) from 12 genes (BAX, BCL2, BID, CASP3, CASP6, CASP7, CASP8, CASP9, CASP10, FAS, FASLG and MCL1) involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer (NSCLC) patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival (P<0.05). After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC (BID rs8190315: P=0.003; CASP9 rs4645981: P=0.007 and FAS rs1800682: P=0.016). A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG (adjusted HR=0.65, 95% CI: 0.49-0.88), CASP9 rs4645981 AA (HR=0.22, 95% CI: 0.07-0.69) and FAS rs1800682 GG (adjusted HR=0.67, 95% CI: 0.46-0.97). Time-dependent receptor operation curve (ROC) analysis revealed that the area under curve (AUC) at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not significantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population. | Songyu Cao Cheng Wang Xinen Huang Juncheng Dai Lingmin Hu Yao Liu Jiaping Chen Hongxia Ma Guangfu Jin Zhibin Hu Lin Xu Hongbing Shen | 2013 | The Journal of Biomedical Research2013,27,3: | 6 |
| 14 | Effect of Jiawei Shenfu decoction on tumor necrosis factor-alpha and nuclear factor-kappa B in patients who have chronic heart failure with syndromes of deficiency of heart Yang显示文摘OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response. | Yu Mei Guo Hangyuan Ye Lingling Bian Jiaping Ma Lijuan Zheng Chunli | 2019 | Journal of Traditional Chinese Medicine2019,39,3: | 6 |
| 15 | Applications of carbon nanotubes in high performance lithium ion batteries显示文摘锂离子电池(解放) 的开发与更高的能力,更高的率能力,和更长的周期生活在电极材料的性能依靠改进。在这篇评论文章,在碳 nanotube (CNT ) 的最近的进展阳极,基于 CNT 的合成电极,和为高效解放的 CNT 当前的收集者被担心。CNT 为 LIB 应用作为候选人材料收到了可观的注意。除了为阳极的一种可能的选择, CNT 在改进最先进的电极材料的表演作为一个答案被认出了。基于 CNT 的合成电极能被机械或化学的途径制作。由于大方面比率和高电的传导性,在很低的装载的 CNT 能导致一个有效传导性的网络。优秀机械力量处于良好的竟技状态结构脚手架建议大潜力提供缩放 nano 的电极材料。因此, CNT 的加入将提高合成电极的电导率,减轻凝块问题,减少不活跃的文件夹上的依赖,并且显著地改进阳极和阴极材料的电气化学的性质。独立 CNT 网络能被用作小当前的收集者增加解放的全面精力密度。最后,为在高效的解放利用 CNT 的研究观点被讨论。 | Yang Wu Jiaping Wang Kaili Jiang Shoushan Fant | 2014 | Frontiers of physics2014,9,3: | 6 |
| 16 | Influence of shrinkage-reducing admixture on drying shrinkage and mechanical properties of high-performance concrete显示文摘High-performance concrete (HPC) has specific performance advantages over conventional concrete in strength and durability. HPC mixtures are usually produced with water/binder mass ratios (mW/mB) in the range of 0.2-0.4, so volume changes of concrete as a result of drying, chemical reactions, and temperature change cannot be avoided. For these reasons, shrinkage and cracking are frequent phenomena. It is necessary to add some types of admixture for reduction of shrinkage and cracking of HPC. This study used a shrinkage-reducing admixture (SRA) for that purpose. Concrete was prepared with two different mW/mB (0.22 and 0.40) and four different mass fractions of SRA to binder (w(SRA) = 0%, 1%, 2%, and 4%). The mineral admixtures used for concrete mixes were: 25% fly ash (FA) and 25% slag by mass of binder for the mixture with mW/mB = 0.40, and 15% silica fume (SF) and 25% FA for the mixture with mW/mB = 0.22. Tests were conducted on 24 prismatic specimens, and shrinkage strains were measured through 120 days of drying. Compressive strength, splitting strength, and static modulus of elasticity were also determined. The results show that the SRA effectively reduces some mechanical properties of HPC. The reductions in compressive strength, splitting tensile strength, and elastic modulus of the concrete were 7%-24%, 9%-19%, and 5%-12%, respectively, after 90 days, compared to concrete mixtures without SRA. SRA can also help reduce drying shrinkage of concrete. The shrinkage strains of HPC with SRA were only as high as 41% of the average free shrinkage of concrete without SRA after 120 days of drying. | Nguyen Quangphu Jiang Linhua Liu Jiaping Tian Qian Do Tienquan | 2008 | Water Science and Engineering2008,1,4: | 5 |
| 17 | Heating graphene to incandescence and the measurement of its work function by the thermionic emission method显示文摘 | Feng Zhu | 2014 | Nano Research2014,7,4: | 5 |
| 18 | Corporate precautionary cash holdings显示文摘 | Seungjin Han Jiaping Qiu | 2006 | Journal of Corporate Finance2006,,1: | 5 |
| 19 | U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population显示文摘在由维持 chromosomal 正直并且阻止染色体的生物变老的一个关键角色结束的 Telomeres 玩熔化。流行病学的研究建议了 telomere 长度的内部个人的差别能影响倾向到多重癌症,但是关于食道的有鳞的房间癌(ESCC ) 的证据仍然是不明确的。几 telomere 在白种人的长度相关的单个核苷酸多型性(TLSNP ) 在染色体宽的协会研究被报导了。然而,在 ESCC 开发的 telomere 长度和 TL-SNPs 的效果是不清楚的。因此,我们进行了盒子控制研究(1045 个 ESCC 案例和 1433 控制) 在中国人口评估在 telomere 长度, TL-SNPs,和 ESCC 风险之间的协会。作为结果, ESCC 案例显示出全面更短的相对 telomere 长度(RTL )( 中部:1.34 ) 比控制(中部:1.50, P < 0.001 ) 。更有趣地,一个明显的非线性的U字形的协会在 RTL 和 ESCC 风险之间被观察( P < 0.001 )与比率(95%信心间隔)等于到 2.40 的机会( 1.843.14 ), 1.36 ( 1.031.79 ), 1.01 ( 0.761.35 ),并且 1.37 ( 1.031.82 )为个人在第一(最短),第二,第三,并且 第5 (最长) quintile 分别地,在是的 第4 quintile 与那些相比引用组。没有重要协会在八报导 TL-SNPs 和 ESCC 危险性之间被观察。这些调查结果建议短或极其长的 telomeres 可以是为在中国人口的 ESCC 的风险因素。 | Jiangbo Du Wenjie Xue Yong Ji Xun Zhu Yayun Gu Meng Zhu Cheng Wang Yong Gao Juncheng Dai Hongxia Ma Yue Jiang Jiaping Chen Zhibin Hu Guangfu Jin Hongbing Shen | 2015 | Frontiers of Medicine2015,9,4: | 4 |
| 20 | A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2显示文摘Mutations and transient conformational movements of the receptor binding domain(RBD)that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).To mitigate viral escape,we developed a cocktail of neutralizing antibodies(NAbs)targeting epitopes located on different domains of spike(S)protein.Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs,targeting the N-terminal domain(NTD)and RBD domain of S,effective at n M concentrations.Remarkably,a combination of RBD-targeting NAbs and NTD-binding NAbs,FC05,enhanced the neutralization potency in cell-based assays and an animal model.Results of competitive surface plasmon resonance assays and cryo-electron microscopy(cryo-EM)structures of antigen-binding fragments bound to S unveil determinants of immunogenicity.Combinations of immunogens,identified in the NTD and RBD of S,when immunized in rabbits and macaques,elicited potent protective immune responses against SARS-CoV-2.More importantly,two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge,without observable antibody-dependent enhancement of infection.These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD. | Li Zhang Lei Cao Xing-Su Gao Bin-Yang Zheng Yong-Qiang Deng Jing-Xin Li Rui Feng Qian Bian Xi-Ling Guo Nan Wang Hong-Ying Qiu Lei Wang Zhen Cui Qing Ye Geng Chen Kui-Kui Lu Yin Chen Yu-Tao Chen Hong-Xing Pan Jiaping Yu Wenrong Yao Bao-Li Zhu Jianping Chen Yong Liu Cheng-Feng Qin Xiangxi Wang Feng-Cai Zhu | 2021 | National Science Review2021,8,8: | 4 |