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Spike protein homology between the SARS-associated virus and murine hepatitis virus implies existence of a putative receptor-binding region

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Chinese Science Bulletin 2003年第11期48卷 1115-1117页

作者： LU Yun chen yinghua Laboratory of Immunology Department of BiologyProtein Science Laboratory of Ministry of Education Tsinghua University Beijing 100084 China

Coronavirus has been determined to be the cause of the recent outbreak of severe acute respiratory syndrome (SARS). Human coronavirus 229E had been studied well and its receptor-binding domain was restricted to aa417—547 of S protein. However, this region has no homology with the newly separated SARS-associated virus (Hong Kong isolate CUHK-W1). Then we analyzed the phylogenesis of S1 subunit of the coronavirus spike protein (SARS-associated virus, Hong Kong isolate CUHK-W1). Interestingly, the highest homology between murine hepatitis virus (MHV) and SARS-associated coronavirus was found. And the important sites (aa62—65 and aa214—216) on the spike protein of MHV with receptor-binding capacity were highly conservative in comparison with the newly separated SARS-asso- ciated virus (the corresponding sites are aa51—54 and aa195—197). These results from bioinformatics analysis might help us to study the receptor-binding sites of SARS-associ- ated virus and the mechanism of the virus entry into the target cell, and design antiviral drugs and potent vaccines.

关键词：非典型性肺炎冠状病毒鼠类肝炎病毒 SARS 蛋白质抗过滤性病源体药物疫苗异体同形

Research on characteristics of water motion and influencing factors for the flexible air chamber jig body

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International Journal of Mining Science and Technology 2015年第3期25卷 389-394页

作者： chen yinghua Kuang Yali Li Haisheng Key Laboratory of Coal Processing and Efficient Utilization of Ministry of Education China University of Mining and Technology

The air bag deformation data were obtained by high-speed dynamic videos experiments. Based on gas–liquid flow VOF model, dynamic mesh technique and deformation data, numerical simulations for different structure models were achieved, and the law of water motion and influencing factors were *** results show that the flow in the length direction of the jig is smooth, and second pulsation appears in the separation time and forms the secondary separation. The installation position of screen and the number of air bags have a great influence on the uniformity of flow and velocity. The screen height cannot be too low to avoid forming the unstable flow. At the same time, the screen height cannot be too high, otherwise water velocity will be too small and was unable to provide enough power. At the height of 1.4m,velocity unevenness is minimum and the best uniform flow can be obtained. Compared with double air bags, there are the following features of single air bag: water flow is not smooth, the time achieving the maximum velocity is too long, maximum velocity is smaller, and overall effect is worse than double air bags.

关键词： Flexible air chamber jig Water motion Numerical simulation Screen location Number of air bags

Molecular epidemiology and evolution of worldwide enterovirus 71 strains isolated from 1970 to 2004

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Chinese Science Bulletin 2007年第11期52卷 1484-1490页

作者： DONG XiaoNan YING Jian chen yinghua Protein Science Laboratory of Ministry of Education/Laboratory of Immunology Department of Biology Tsinghua University Beijing100084 China

Human enterovirus 71 (EV71) is one of the major etiological agents of the hand-foot-and-mouth disease (HFMD) that often causes severe neurological complications. Recently,its outbreaks mainly take place in the torrid zone of the Asia-Pacific region. To study the evolution and genetic variability,we collected 532 EV71 strains with almost complete or complete VP1 sequences (891 nt) isolated worldwide from 1970 to 2004. The pairwise homologies and genetic distances were analyzed. Most strains belong to previously identified genotype B and C. However,a unique strain R13223-IND-01 appears not to fall into current three genotypes (A,B and C),and probably represents a new genotype D. Some orphan strains were observed in the genotypes B and C,and their significance in the EV71 evolution was discussed. Moreover,there is a significant co-variance of 6 discrete positions on VP1 (amino acid 43,58,164,184,240 and 249). This high co-variability is tightly related with the subgenotypes.

关键词：肠道病毒71 流行病学可变性钴

Strategy against micrometastasis of epithelial cancer: Detection and elimination

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Chinese Science Bulletin 2002年第17期47卷 1415-1421页

作者： QIN Li XIAO Yi chen yinghua Laboratory of Immunology Research Centre for Medical Science and Department of BiologyTsinghua UniversityProtein Science Laboratory of MOEBeijing 100084China

Tumor metastasis is generally agreed to be the major cause of cancer death. Over the last few years, studies of new diagnosis techniques and tumor immunotherapy have made great progress. Recent clinical studies on the occult metastases of breast, lung and colorectal cancer all suggested that the detection of micrometastases in bone marrow is prognostically important and provides substantial evidence of tumor dissemination. On the other hand, two kinds of the mAb-based immunotherapy have been approved for the treatment against epithelial cancer. Monoclonal antibody (mAb) 17-1A for colorectal carcinomas and mAb herceptin for breast cancer both have produced good curative effects. Potential therapeutics based on some antibodies with prominent antitumor activity also has shown obvious clinical effect. These studies indicate that detection of micrometasta-sis in circulatory system and immunotherapy by eliminating metastatic malignant cells suggested a new strategy against the metastatic cancer.

关键词： tumor micrometastasis detection elimination immu-notherapy mAb.

Inhibition of ciliary neurotrophic factor in a rat model of transected spinal cord

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Neural Regeneration Research 2011年第2期6卷 112-117页

作者： Hua Jin Yanhua Li yinghua chen Junhong Li Binghua chen Tinghua Wang Department of Anesthesiology Kunhua Hospital Kunming Medical College Kunming 650032 Yunnan Province China Institute of Neuroscience Kunmincl Medical College Kunming 650031 Yunnan Province China Laboratory of Neurological Disease Sichuan University Chengdu 610041 Sichuan Province China

Ciliary neurotrophic factor （CNTF） dramatically increases following spinal cord injury and participates in the repair process, although some studies have shown that CNTF plays a role in promoting glial scar formation following spinal cord injury. The antibody closure model can be used to inhibit CNTF expression following spinal cord injury, thereby furthering the understanding of the role of CNTF in spinal cord injury repair. In the present experiment, spinal catheters were placed in the vertebral canal of spinal cord transected rats, and CNTF antibodies were injected following fixation of the paraspinal muscle catheter. At 24 hours after a single CNTF antibody injection, CNTF expression decreased in the thoracic and lumbar spinal cord and recovered to normal levels by 48 72 hours. CNTF antibody treatment can effectively block endogenous CNTF expression in the thoracic and lumbar spinal cord during an interval of less than 24 hours in transected rats.

关键词： ciliary neurotrophic factor antibody intrathecal injection spinal cord transection rats

Induction of multi-epitope-specific antibodies against HIV-1 by multi-epitope-vaccines

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Chinese Science Bulletin 2001年第22期46卷 1859-1864页

作者： DING Jian HE Fei LU Yun XIAO Yi chen yinghua Laboratory of Immunology Research Center for Medical Science and Department of BiologyTsinghua UniversityProtein Science Laboratory of Ministry of Education of ChinaBeijing 100084China

Some neutralizing antibodies against HIV-1 envelope proteins were highly effective to inhibit the infection of different strains in vitro, and existed in the infected individuals with very low levels. We suggested multi-epi-tope-vaccine as a new strategy to increase levels of neutralizing antibodies and the abilities against HIV mutation in vivo. Two candidate multi-epitope-vaccines induced antibodies with predefined multi-epitope-specificity in rhesus macaque. These antibodies recognized corresponding neutralizing epitopes on epitope-peptides, gp41 peptides, V3 loop peptide, rsgp41 and rgp120. Besides, three candidate epi-tope-vaccines in combination (another kind of multi-epitope-vaccines) showed similar potency to induce predefined multiple immune responses in rabbits. These results suggest thatmulti-epitope-vaccines may be a new strategy to induce multi-antiviral activities against HIV-1 infection and mutations.

关键词： HIV-1 multi-epitope-vaccine neutralizing epitope.

Multiple metal sources in polymetallic W-Sn ore deposits revealed by mercury stable isotopes

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Science China Earth Sciences 2024年第11期67卷 3465-3475页

作者： Zhendong TIAN Bernd LEHMANN Changzhou DENG Xingchun ZHANG Anbo LUO yinghua chen Runsheng YIN State Key Laboratory of Ore Deposit Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China Mineral Resources Technical University of ClausthalClausthal-Zellerfeld 38678Germany Faculty of Land Resource Engineering Kunming University of Science and TechnologyKunming 650093China

Granite-related W-Sn ore systems are commonly associated with coeval Pb-Zn mineralization. It remains unclear whether these metals are derived from the same sources or not. Mercury(Hg) is a common minor component in such systems. Hg isotopes undergo unique mass-independent fractionation(expressed as Δ^(199)Hg values), which is mainly generated during Hg photochemical reactions on Earth's surface and not affected by magmatic-hydrothermal processes, offering an excellent opportunity to trace metal sources in hydrothermal systems. We observed near-zero Δ^(199)Hg values in wolframite(-0.10‰ to0.08‰, n=11), and in skarn-(-0.17‰ to 0.12‰, n=48) and greisen-type(-0.12‰ to 0.10‰, n=11) bulk tin-tungsten ore from eight major ore deposits in South China. These values are identical to those of coeval highly evolved granites(-0.13‰ to 0.12‰,n=49), supporting that Hg in W-Sn ores were sourced from granite. However, sulfides(e.g., pyrite, chalcopyrite, arsenopyrite,galena, and sphalerite) in these deposits exhibit negative to near-zero Δ^(199)Hg values(-0.42‰ to 0.09‰, n=124), which indicates a contribution of Hg and by inference other metals from both Precambrian basement rocks(Δ^(199)Hg<0) and ore-related *** study demonstrates that multiple sources of metals were involved in the formation of the polymetallic W-Sn deposits, and further highlights that extraction of metals from basement rocks may be a critical control on the formation of economically important mineralization of base metal sulfides(e.g., Pb, Zn) in granite-related magmatic-hydrothermal systems.

关键词： Tin-tungsten deposit Mercury isotope Metal source Metal zonation South China

10E8-like neutralizing antibodies against HIV-1 induced using a precisely designed conformational peptide as a vaccine prime

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Science China(Life Sciences) 2014年第1期57卷 117-127页

作者： YU Yang TONG Pei LI Yu LU ZhiFeng chen yinghua Laboratory of Immunology School of Life Sciences Tsinghua University Beijing Key Laboratory for Protein Therapeutics MOE Key Laboratory for Protein Sciences

Recent studies have demonstrated that the membrane-proximal external region （MPER） of human immunodeficiency virus 1 （HIV-1） glycoprotein 41 contains a series of epitopes for human monoclonal antibodies, including 2F5, Zl3el, 4El0, and 10E8, which were isolated from HIV-l-infected individuals and show broad neutralizing activities. This suggests that MPER is a good target for the development of effective HIV-1 vaccines. However, many studies have shown that it is difficult to induce antibodies with similar broad neutralizing activities using MPER-based peptide antigens. Here, we report that 10E8-1ike neu- tralizing antibodies with effective anti-HIV-1 activity were readily induced using a precisely designed conformational immu- nogenic peptide containing the 10E8-specific epitope. This immunogenic peptide （designated T10HE） contains a 15-mer MPER-derived 10E8-specific epitope fused to T-helper-cell epitopes from tetanus toxin （tt）, which showed a significantly sta- bilized a-helix structure after a series of modifications, including substitution with an （S）-c^-（2＇-pentenyl） alanine containing an olefin-bearing tether and ruthenium-catalyzed olefin metathesis, compared with the unmodified T10E peptide. The stabilized （x-helix structure of T10HE did not affect its capacity to bind the 10E8 antibody, as evaluated with an enzyme linked immuno- sorbent assay （ELISA） and surface plasmon resonance binding assay （SPR assay）. The efficacies of the T10HE and T10E epitope vaccines were evaluated after a standard vaccination procedure in which the experimental mice were primed with ei- ther the T10HE or T10E immunogen and boosted with HIV-1 JRFL pseudoviruses. Higher titers of 10E8-1ike antibodies were induced by T10HE than that by T10E. More importantly, the antibodies induced by T10HE showed enhanced antiviral potency against HIV-1 strains with both X4 and R5 tropism and a greater degree of broad neutralizing activity than the antibodies in- duced by T10E. These results indic

关键词： MPER peptide immunogen vaccine prime neutralizing antibody

Diagenesis and Porosity of the Cambrian-Ordovician Carbonate Shoal Fades at Yangjiaping, Shimen, Hunan

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Acta Geologica Sinica(English Edition) 2000年第1期74卷 29-45,116-117页

作者： ZHANG Xiulian, WANG yinghua and chen Xiaolong Department of Geology, Peking University, Beijing 100871 Peking Univ Dept Geol Beijing 100871 Peoples R China

Upper Cambrian-Lower Ordovician shoal-facies carbonate rocks are well developed in the Yangjiap-ing section, Shimen, Hunan, and their types are also highly varied. There are both monomictic shoal-facies rocks (e.g. sparite oolitic limestone and sparite calcarenite) and polymictic shoal-facies rocks (e.g. grainstone, whose grain types include sand- and pebble-sized fragments, bioclasts, oolites, algal mats etc.). What is different is that the Upper Cambrian shoal-facies rocks have been mostly strongly dolomitized into shoal-facies dolomite with various residual textures. This paper presents an in-depth study of various kinds of diagenesis and pore space evolution occurring in this section and suggests that the diagenetic sequences of shoal-facies rocks in the study area is dominantly of retrogressive type.

关键词： rock types dolomitization dissolution diagenetic sequence