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Design,synthesis,and screen of cathepsin K inhibitors

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Chinese Chemical Letters 2013年第8期24卷 715-718页

作者： Ying-Ying Yu Wei Sun Lei dong hai-dong liu Dan Jiang Jun-hai Xiao Xiao-Hong Yang Song Li School of Pharmaceutical Sciences Jilin University Laboratory of Computer-Aided Drug Design and Discovery Beijing Institute of Pharmacology and Toxicology First Affiliated Hospital of Jilin University

We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e,9d,9p,9j and 9k （IC_（50）≤0.005μmol/L） were equal to or greater than that of the lead compound *** hydrophobic compounds showed weaker potency,which can be explained by the hydrophobic nature of the cathepsin K binding pockets.

关键词： Epoxysuccinic acid derivatives Synthesis Inhibitors Cathepsin K

Common SNPs of APM1 Gene Are Not Associated With Hypertension or Obesity in Chinese Population

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Biomedical and Environmental Sciences 2006年第3期19卷 179-184页

作者： WEI-LI YAN SHU-FENG CHEN JIAN-FENG HUANG YAN SHENA BO-QIN QIANG dong-hai liu dong-FENG GU Division of Population Genetics and Prevention Cardiovascular Institute and Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College 167 Beilishi Road Beijing 100037 China National Human Genome Center North Yongchang Rd 3-707 Beijing 100176 China

Objective To investigate whether the common variants 45T/G and 276G/T in APM1 gene were associated with hypertension combined with obesity （HO） and related clinical features in Chinese Han population. Methods A case-control study design was applied. Common polymorphisms of 45T/G and 276G/T were genotyped by PCR product sequencing in 484 cases with HO and 502 controls with normal blood presure and BMI 〈 25. Results The genotype and allele frequencies of 45T/G, 276G/T, and haplotype defined by the two variants in cases did not differ from those in controls. The means of blood pressure, BMI and waist-hip ratio did not differ among genotypes of the two polymorphisms and haplotypes. Among lipid profiles, only serum high-density lipoprotein cholesterol （HDL-C） levels were significantly lower in T allele carders than that in non-T carriers after adjusting possible confounding factors （1.21 vs 1.32 mmol/L, P=0.0001）. Condusion Polymorphisms of 45T/G and 276G/T in APM1 gene are not associated with hypertension or obesity, or their clinical features in Chinese Han population. Common polymorphism of 45T/G might be associated with serum HDL-C levels in Chinese.

关键词： Adiponectin HDL-C Hypertension Obesity

Strength and ductility optimization of HPDC AlSi8MgCuZn2 alloys by modifying pre-aging treatment

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China Foundry 2024年第4期21卷 343-351页

作者： Yuan-hang Jiang Hui-ting Zheng Fei liu hai-dong Zhao National Engineering Research Center of Near-net Shape Forming for Metallic Materials South China University of TechnologyGuangzhou 510641China

Considering the components produced by high pressure die casting(HPDC)process usually with ultra-large sizes and complex morphologies,high temperature solid solution treatment is not a suitable method to further improve their mechanical *** this study,two-stage aging treatment with different pre-aging times was designed and employed to further improve the mechanical properties of HPDC Al8SiMgCuZn *** characteristics of precipitates were evaluated by a transmission electron microscope(TEM),and the precipitation strengthening mechanism was *** results reveal that the strengthening is mainly contributed by the precipitation ofβ″phase after two-stage aging,and the number density and size of the precipitates are significantly depended on the pre-aging *** number density of precipitates is increased with the pre-aging time prolonged from 0 h to 4 h,and then decreases with the further increase of pre-aging time from 4 h to 6 *** precipitates with the highest density and smallest size are observed after pre-aging for 4 *** pre-aged at 100℃for 4 h and then artificial aged at 200℃for 30 min,the yield strength of 207 MPa,ultimate tensile strength of 325 MPa and elongation of 7.6%are achieved.

关键词： high pressure die cast aluminum alloy microstructural heterogeneity mechanical properties precipitation strengthening two-stage aging

Investigating the Absorption and Desorption Behavior of Methylene Chloride in the Poly(aryl ether ketone) Film with Different Crystallinities

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Chinese Journal of Polymer Science 2024年第2期42卷 239-246,I0009页

作者： Hong-Ru Yang Jin-dong Zhang dong-Ting Gao Gang liu Chun-hai Chen Jia-Nan Yao Center for Advanced Low-Dimension Materials State Key Laboratory for Modification of Chemical Fibers and Polymer MaterialsCollege of Materials Science and EngineeringDonghua UniversityShanghai201620China

Poly(aryl ether keton e)(PAEK) films with different crystallinities were obtained by controlling the cooling rate,which were subjected to the absorption and desorption of methylene chloride(CH_(2)Cl_(2)).We employed attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopy analyses to investigate the diffusion behavior of CH_(2)Cl_(2) in PAEK films with different *** to the Fickian diffusion model,the calculated diffu sion coefficients of CH_(2)Cl_(2) in PAEK films were observed to decrease with increasing *** effect of CH_(2)Cl_(2)absorption and desorption on the mechanical properties of PAEK films with different crystallinity was further analyzed using tensile *** tensile tests exhibited that CH_(2)Cl_(2) has two concurrent effects:plasticization and solvent-induced *** scanning calorimetry(DSC) and wide-angle X-ray diffraction(WXRD) techniques further confirmed solvent-induced crystallization *** results would be beneficial to understand the solvent resistance of PAEK materials and consequently provide the practical application conditions of PAEK with a theoretical basis.

关键词： Poly(aryl ether ketone) Diffusion behavior Infrared spectra Solvent-induced crystallization Mechanical properties

Characteristics and distribution of microstructures in high pressure die cast alloys with X-ray microtomography:A review

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China Foundry 2024年第5期21卷 427-444页

作者： hai-dong Zhao Xue-ling Wang Qian Wan Wen-hui Bai Fei liu School of Mechanical and Automotive Engineering South China University of TechnologyGuangzhou 510640China

Al and Mg alloy high pressure die castings(HPDC)are increasingly used in automotive *** microstructures in the castings have decisive effect on the casting mechanical properties,in which the microstructure characteristics are fundamental for the investigation of the microstructure-property *** the past decade,the microstructure characteristics of HPDC Al and Mg alloys,especially micro-pores andα-Fe,have been investigated from two-dimensional(2D)to threedimensional with X-ray micro-computed tomography(μ-CT).This paper provides an overview of the current understanding regarding the 3D characteristics and formation mechanisms of microstructures in HPDC alloys,their spatial distributions,and the impact on mechanical ***,it outlines future research directions for the formation and control of heterogeneous microstructures in HPDC alloys.

关键词： high pressure die casting microstructure three-dimensional characteristics distribution Al and Mg alloys

Coordination-driven self-assembly of a molecular 818knot and molecular borromean rings

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Science China Chemistry 2024年第11期67卷 3652-3656页

作者： Xiang Gao dong liu hai-Ning Zhang Guo-Xin Jin Department of Chemistry Fudan University

We report the facile construction of a molecular 818knot and a molecular Borromean rings assembly through self-assembly directed by Cp*Rh corner units. Two curved ligands of similar size and shape were used in this study. The slight steric differences between the two ligands induce the formation of distinctly different topologies of the assembled products. The structures were confirmed by single-crystal X-ray analysis and nuclear magnetic resonance spectroscopy.

关键词： coordination-driven Cp*Rh 818 knot Borromean rings

Comprehensive study on the spatial distribution of heavy metals and their environmental risks in high-sulfur coal gangue dumps in China

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Journal of Environmental Sciences 2024年第2期136卷 486-497页

作者： Yingbo dong Huan Lu hai Lin School of Energy and Environmental Engineering University of Science and Technology BeijingBeijing 100083China Beijing Key Laboratory on Resource-oriented Treatment of Industrial Pollutants Beijing 100083China

The accumulation of coal gangue(CG)from coal mining is an important source of heavy metals(HMs)in *** spatial distribution and environment risk assessment are extremely important for the management and remediation of *** soil samples were collected from the high-sulfur CG site in northern China and analyzed for six *** results showed that the soil was heavily contaminated by Mn,Cr and Ni based on the Nemerow index,and posed seriously ecological risk depended on the geo-accumulation index,potential ecological risk index and risk assessment *** semi-variogram model and ordinary kriging interpolation accurately portrayed the spatial distribution of ***,Mn,and Cr were distributed by band diffusion,Ni was distributed by core,the distribution of Cu had obvious patchiness and Zn was more *** spatial autocorrelation indicated that all HMs had strong spatial *** BCR sequential extraction was employed to qualify the geochemical fractions of *** data indicated that Fe and Cr were dominated by residual fraction;Cu,Ni and Zn were dominated by reducible and oxidizable fractions;Mn was dominated by reducible and acid-extractable(25.38%-44.67%)*** correlation analysis showed that pH was the main control factor affecting the non-residue fractions of ***,acid production from high sulfur CG reduced soil pH by 2-3,which indirectly promoted the activity of ***,the conceptual model of HMs contamination at the CG site was proposed,which can be useful for the development of ecological remediation strategies.

关键词： High-sulfur coal gangue Soil contamination Heavy metals Spatial distribution Geochemical fractions Risk assessment

Beam and image experiment of beam deflection electron gun for distributed X-ray sources

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Nuclear Science and Techniques 2019年第3期30卷 127-138页

作者： Cheng-Jun Tan Chuan-Xiang Tang Wen-Hui Huang Qing-Xiu Jin Ying-Chao Du Qun Luo Pei-dong Wu dong-hai liu Lu-Ming Zhang Cong Xu Accelerator Laboratory Department of Engineering PhysicsTsinghua University Key Laboratory of Particle and Radiation Imaging Ministry of Education Tsinghua University Nuctech Company Limited

Distributed X-ray sources comprise a single vacuum chamber containing multiple X-ray sources that are triggered and emit X-rays at a specific time and location. This process facilitates an application for innovative system concepts in X-ray and computer tomography. This paper proposes a novel electron beam focusing, shaping,and deflection electron gun for distributed X-ray *** electron gun uses a dispenser cathode as an electron emitter, a mesh grid to control emission current, and two electrostatic lenses for beam shaping, focusing, and deflection. Novel focusing and deflecting electrodes were designed to increase the number of focal spots in the distributed source. Two identical half-rectangle opening electrodes are controlled by adjusting the potential of the two electrodes to control the electron beam trajectory, and then, multifocal spots are obtained on the anode target. The electron gun can increase the spatial density of the distributed X-ray sources, thereby improving the image quality. The beam experimental results show that the focal spot sizes of the deflected(deflected amplitude 10.5 mm)and non-deflected electron beams at full width at half maximum are 0.80 mm 90.50 mm and 0.55 mm 90.40 mm, respectively(anode voltage 160 kV; beam current 30 mA). The imaging experimental results demonstrate the excellent spatial resolution and time resolution of an imaging system built with the sources, which has an excellent imaging effect on a field-programmable gate array chip and a rotating metal disk.

关键词： Beam deflection electron gun X-ray imaging Distributed X-ray sources Stationary CT

Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells

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Asian Journal of Andrology 2024年第2期26卷 165-174页

作者： hai-Wei Feng Yu Zhao Yan-Ling Gao dong-Teng liu Li-Jun Huo Key Laboratory of Agricultural Animal Genetics Breeding and ReproductionEducation Ministry of ChinaCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Shenzhen Key Laboratory of Fertility Regulation Reproductive Medicine CenterThe University of Hong Kong-Shenzhen HospitalShenzhen 518053China Maternal-Fetal Medicine Institute Department of Obstetrics and GynaecologyShenzhen Baoan Women's and Children's HospitalJinan UniversityShenzhen 518100China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various *** mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial *** has been implicated in meiosis regulation,but its precise role is currently *** this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in *** found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the ***,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition *** loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB *** dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron ***,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) *** together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关键词： ClpX homologous chromosome meiosis mitochondrial recombination synapsis