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Current status and challenges in drug discovery against the globally important zoonotic cryptosporidiosis

Animal Diseases 2021年第1期1卷 48-57页

作者： Guan Zhu jigang yin Gregory D.Cuny Key Laboratory of Zoonosis Research Ministry of Education/Institute of Zoonosis/and College of Veterinary MedicineJilin UniversityChangchunChina Department of Pharmacological&Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTXUSA.

The zoonotic cryptosporidiosis is globally distributed,one of the major diarrheal diseases in humans and *** oocysts are also one of the major environmental concerns,making it a pathogen that fits well into the One Health *** its importance,fully effective drugs are not yet ***-cryptosporidial drug discovery has historically faced many unusual challenges attributed to unique parasite biology and technical *** significant progresses have been made recently,anti-cryptosporidial drug discovery still faces a major obstacle:identification of systemic drugs that can be absorbed by patients experiencing watery diarrhea and effectively pass through electron-dense(ED)band at the parasite-host cell interface to act on the epicellular *** may be a need to develop an in vitro assay to effectively screen hits/leads for their capability to cross ED *** the meantime,non-systemic drugs with strong mucoadhesive properties for extended gastrointestinal exposure may represent another direction in developing anti-cryptosporidial *** developing both systemic and non-systemic drugs,a non-ruminant animal model exhibiting diarrheal symptoms suitable for routine evaluation of drug absorption and anti-cryptosporidial efficacy may be very helpful.

关键词： Cryptosporidium Cryptosporidiosis Drug discovery Watery diarrhea Electron-dense band Drug delivery

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HES-C-axis large diameter(6" and 8") sapphire technology for LED Applications

HES-C-axis large diameter(6" and 8") sapphire technology for...

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第十六届全国晶体生长与材料学术会议

作者： jigang yin Rick Schwerdtfeger Advanced Renewable Energy Company LLC(ARC Energy)

Manufacturing of high‐brightness LEDs(HB‐LED) requires c‐plane sapphire *** a‐axis sapphire growth processes grow boules on a‐axis and inefficiently extract c‐axis cores perpendicular to the growth direction of the *** limits sapphire material utilization for LED manufacturing to less than 35%.ARC Energy’s CHES(Controlled Heat Extraction System) crystal growth process grows high quality sapphire on c‐axis,increasing material utilization to as much as 80% and significantly reducing the cost of large diameter sapphire wafers for HB‐LED *** free sapphire boules have been grown and the CHES furnaces are automated to meet high quality standards with reproducibility and consistency in manufacturing *** Manufacturing Data will also be presented which showcase that LEDs produced on CHES PSS wafers have higher light output than LEDs produced from traditional a‐axis *** industry’s intent to utilize 150‐mm diameter wafers are addressed by growing 170‐mm diameter,c‐axis,near‐net shape sapphire *** same furnace can be used to grow 220‐mm diameter boules for 200‐mm diameter *** to meet the demand for semiconductor scale large diameter 150‐mm and 200‐mm diameter sapphire wafers with CHES will be discussed.

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Unique Tubulin-Based Structures in the Zoonotic Apicomplexan Parasite Cryptosporidium parvum

Unique Tubulin-Based Structures in the Zoonotic Apicomplexan...

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2021中国畜牧兽医学会兽医寄生虫学分会第二届青年科学家学术论坛

作者： Chenchen Wang jigang yin Guan Zhu Key Laboratory for Zoonoses Research of the Ministry of Education Institute of Zoonosis College of Veterinary Medicine Jilin University

Cryptosporidium parasites are known to be highly divergent from other apicomplexan species at evolutionary and biological *** we provide evidence showing that the zoonotic Cryptosporidium parvum also differs from other apicomplexans,such as Toxoplasma gondii,by possessing only two tubulin-based filamentous structures,rather than an array of subpellicular *** an affinity-purified polyclonal antibody against *** β-tubulin(CpTubB),we observed a long and a short microtubule that are rigid and stable in the sporozoites and restructured during the intracellular parasite *** asexual development(merogony),the two restructuring microtubules are present in pairs(one pair per nucleus or merozoites).In sexual developmental stages,tubulin-based structures are detectable only in microgametes,but undetectable in *** observations indicate that *** parasites use unique microtubule structures that differ from other apicomplexans as part of their cytoskeletal elements.

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Cryptosporidium parvum thrombospondin type 1 domain-containing protein 4(CpTSP4):Discovery and determination of a heparin-binding site(HBS) and contribution of HBS to the adhesion of sporozoites onto host cells

Cryptosporidium parvum thrombospondin type 1 domain-containi...

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2021中国畜牧兽医学会兽医寄生虫学分会第16次学术研讨会

作者： Guan Zhu Dongqian Wang jigang yin Meng Li Institute of Zoonosis Jilin University

The zoonotic apicomplexan Cryptosporidium parvum contains a number of adhesive proteins including at least 12 thrombospondin type 1(TSP1) domain-containing proteins(CpTSPs).In addition to TSP1 domain,TSPs may contain other structural domains such as Apple,Notch/Lin,Kringer,and/or EGF-like domains assumedly for interacting with various *** are implicated as important molecules for parasite motility and adhesion onto host cell surfaces,but never been experimentally *** the present study,we focused on CpTSP4,one of the *** TSPs that contains two Apple and two TSP1-like domains and is expressed as a surface protein in *** have discovered that CpTSP4 possesses heparin-binding activity and biochemically determined the motif responsible for interacting heparin that differs from classic motifs and is located within one of the Apple *** also determined the CpTSP4-heparin binding kinetics,and confirmed the involvement of CpTSP4 in the adhesion of sporozoites and heparin and/or heparin sulfate as a ligand for CpTSP4 and *** data has not only revealed a new heparin-binding motif and expanded the heparin-binding protein family to include TSP proteins,but also open a new direction to investigate the roles of the CpTSPs and various domains in the parasite adhesion onto and invasion into host cells.

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Discovery of new microneme proteins in Cryptosporidium parvum and implication of the involvement of a rhomboid membrane protein(CpROM1)in the parasite invasion and proteostasis of parasitophorous vacuole membrane and feeder organelle

Discovery of new microneme proteins in Cryptosporidium parvu...

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2021中国畜牧兽医学会兽医寄生虫学分会第二届青年科学家学术论坛

作者： Xin Gao Dongqiang Wang jigang yin Guan Zhu Key Laboratory of Zoonosis Research of the Ministry of Education the Institute of Zoonosis and the College of Veterinary Medicine Jilin University

Apicomplexan parasites possesses several unique secretory organelles including rhoptries,micronemes and dense granules that play critical roles in the invasion of host *** contents of these organelles and their biological roles are better studied in Toxoplasma and Plasmodium,but underappreciated in Cryptosporidium that contains many medically and veterinarily important *** micronemes,only four proteins were previously identified or proposed to be located in this organelle,and one of them(GP900) was confirmed by immunogold electron microscopy(IEM) for its presence in the micronemes of intracellular *** we report the discovery of four new microneme proteins(MICs) in the sporozoites of the zoonotic species *** evidenced by immunofluorescence assay(IFA),including proteins encoded by cgd380,cgd1550,cgd1680 and cgd2590 *** them,the presence of cgd380 product in the micronemes of sporozoites was further confirmed by ***380 encodes one of the three rhomboid peptidases(ROMs) encoded by the *** genome,thus designated as *** IEM also confirmed the presence of CpROMl in the micronemes of intracellular merozoites,parasitophorous vacuole membranes(PVM) and feeder organelle(FO).CpROMl was enriched to the pellicles and concentrated at the host cell-parasite interface during the invasion of sporozoites and its transformation to *** transcript levels of CpROM1 gene were also much higher in oocysts and excysted *** observations were indicative that CpROMl as an intramembrane peptidase known for membrane proteolytic activity was involved in the parasite invasion and proteostasis of parasitophorous vacuole membrane and feeder organelle.

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Detection of antibody responses in mice infected with Cryptosporidium parvum using four kinds of antigens

Detection of antibody responses in mice infected with Crypto...

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中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会

作者： Jing Liu Tianyu Zhang Kejie Wang Qingyan Shao Huijun lu Ning Jiang Qijun Chen jigang yin Key Laboratory of Zoonosis Ministry of Education Jilin University Key Laboratory of Zoonosis Shenyang Agricultural University

Background:Cryptosporidium parvum is a protozoan parasite that causes diarrheal illness in a wide range of mammalian hosts,including *** in serologic assays for Cryptosporidium parvum have made serology an attractive surveillance *** this end,developement highly sensitive and costly effective antigens are urgently needed.

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microRNA profiling in the parasite Neospora caninum using a high-throughput approach

microRNA profiling in the parasite Neospora caninum using a ...

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中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会

作者： Gang Liu lijun Jia Shoufa Zhang Kejie Wang Qingyan Shao Tianyu Zhang Huijun lu Ning Jiang Qijun Chen jigang yin Key Laboratory of Zoonosis Ministry of Education Jilin University Department of Veterinary Medicine Agriculture College of Yanbian University Key Laboratory of Zoonosis Shenyang Agricultural University

Background:Neospora caninum is an important veterinary pathogen that causes spontaneous abortion in *** the intermidiate hosts,the parasite can undergo rapid development or remain inactive in the *** mechanism that regulates parasite proliferation has not been fully *** noncoding RNAs(snc RNA)such as micro RNAs(miR NAs)are endogenous

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原油掺混脱硫剂过程中的热危险性

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石油学报（石油加工） 2013年第4期29卷 706-711页

作者：郭耸殷继刚彭敏君万伟余罕元陈晨南京理工大学化工学院安全工程系江苏南京210094 中国五洲工程设计有限公司北京100053

采用C80微量量热仪研究了原油以及2种典型脱硫剂TS02和JH02与原油掺混物的热分解特性,在此基础上分别计算了活化能、指前因子等反应动力学参数,对比分析了2种脱硫剂对原油热分解过程的影响规律。结果表明,原油在掺混脱硫的过程中,起始... 详细信息

采用C80微量量热仪研究了原油以及2种典型脱硫剂TS02和JH02与原油掺混物的热分解特性,在此基础上分别计算了活化能、指前因子等反应动力学参数,对比分析了2种脱硫剂对原油热分解过程的影响规律。结果表明,原油在掺混脱硫的过程中,起始分解温度和反应活化能均有所降低,反应放热量增大,自加速分解温度(SADT)变低,原油和脱硫剂掺混物的热危险性远大于纯原油,并且JH02脱硫剂对原油脱硫过程的影响大于TS02脱硫剂。

关键词：原油脱硫剂热危险性热解动力学自加速分解温度(SADT)

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