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71.
Shen M Zhang L Lee KM Vermeulen R Hosgood HD Li G Yin S Rothman N Chanock S Smith MT Lan Q 《Experimental & molecular medicine》2011,43(6):374-378
Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P<0.05) and SNP analyses (FDR<0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary. 相似文献
72.
Kim BJ Kim SY Cho YS Kim BJ Han BG Park EK Lee SH Kim HY Kim GS Lee JY Koh JM 《Experimental & molecular medicine》2011,43(2):71-81
There is increasing evidence of a biochemical link between lipid oxidation and bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density lipoprotein (LDL) and metabolizes biologically active phospholipids in oxidized LDLs. Here, we performed association analyses of genetic variation in PON1 to ascertain its contribution to osteoporotic fractures (OFs) and bone mineral density (BMD). We directly sequenced the PON1 gene in 24 Korean individuals and identified 26 sequence variants. A large population of Korean postmenopausal women (n=1,329) was then genotyped for eight selected PON1 polymorphisms. BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment, and the occurrence of non-vertebral fractures (i.e., wrist, hip, forearm, humerus, rib, and pelvis) was examined using self-reported data. Multivariate analyses showed that none of the polymorphisms was associated with BMD at either site. However, +5989A>G and +26080T>C polymorphisms were significantly associated with non-vertebral and vertebral fractures, respectively, after adjustment for covariates. Specifically, the minor allele of +5989A>G exerted a highly protective effect against non-vertebral fractures (OR=0.59, P=0.036), whereas the minor allele of +26080T>C was associated with increased susceptibility to vertebral fractures (OR=1.73, P=0.020). When the risk for any OFs (i.e., vertebral or non-vertebral) was considered, the statistical significance of both polymorphisms persisted (P=0.002-0.010). These results suggest that PON1 polymorphisms could be one of useful genetic markers for OF risk in postmenopausal women. 相似文献
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This paper exemplifies discrete analogs obtained by transformation of the continuum equations governing porous media flow to a system of algebraic equations. To give insight in the underlying physics, the numerical examples are worked out algebraically. The volume-centered approximation turns out to be a reasonable simplification of the algebraically exact face-centered method. 相似文献
76.
The crystal structure of deoxyguanosine (5′) phosphate, disodium salt, (5′-dGMP Na2 4H2O) has been determined from three dimensional single crystal x-ray data collected by multiple film, equi-inclination, Weissenberg method using CuKa radiation. The crystal belongs to the monoclinic space groupP21 witha=16.002±0.003 Å,b=10.730±0.003 Å,c=5.575±0.005 Å andβ=101.9°. The structure was solved by symbolic addition method using the program Multan, the reliability index being 0.090. The guanine base is in the usualanti conformation about the C (1′)-N (9) bond withx CN=52.3°. The structure shows two unique conformational features not observed in any nucleotide structure reported so far. The deoxyribose moiety shows O (1′)endo puckering with respect to the best four atom plane defined by C(1′)-C(2′)-C(3′)-C(4′). The conformation about the C(4′)-C(5′) bond isgauche-trans with ø00=62.5° and øoc=174.8°. This is the first nucleotide structure where agt conformer similar to that found in the Watson-Crick double helical DNA model has been experimentally observed. These two conformational features have also direct relevance to the concept of ‘a conformationally rigid nucleotide unit’ developed by Sundaralingam. The nine membered guanine ring is essentially planar. Bases of molecules related by a ‘c’ cell translation tend to overlap, the shortest distance being 3.51 Å between the atoms N (3) and C(8). One of the sodium atoms Na(1) has an octahedral coordination with four water oxygens and O(6) and O(3′) atoms occupying the corners at distances ranging from 2.35 Å to 2.55 Å. 相似文献
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A variety of novel 2-alkylthiopyrimidines were synthesized through simple condensation of arylidenemalononitriles with different 2-alkylthiouronium halide derivatives catalyzed by anhydrous potassium carbonate (K2CO3). The reactions have been carried out under mild conditions in i-PrOH, and the products were obtained in moderate to good yields with a simple work-up method. Subsequently, some examples of these compounds have been converted into Tacrine analogs by applying the Friedländer reaction. 相似文献
80.
Dr. Qiuhua Liu Wanjie Ren Siwei Zhang Dr. Yang Huang Dilong Chen Dr. Wennan Zeng Prof. Dr. Zaichun Zhou Prof. Dr. Lin He Prof. Dr. Wenping Guo Prof. Dr. Jianfeng Li 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(8):e202103892
Both geometric architecture and electronic configurations of heme proteins contribute to its activity. In this work we designed and synthesized a series of four copper(II) porphyrin complexes ( 4 -, 3 -, 2 - and 1 -Cu) where the molecular conformations are modulated by a pair of stepwise shortened straps on the same porphyrin side (cis-ortho) to give double bow-shaped skeletons. Single crystal structures demonstrate that the straps gradually increase the saddle deformation and the deviation of the metal centers, which is in accordance with two, unusual d-orbital reconstructions of two different ground states, as revealed by 4 K EPR and DFT calculations. In the study of the electrocatalytic hydrogen evolution reaction (HER), 1 -Cu, with the shortest straps, showed the most apparent improvement of activity. Second coordination sphere (SCS) effects created by the double bow-shaped architecture and the strong saddle porphyrin core in 1 -Cu are found to play key roles in proton trapping during the catalytic process. The work contributes a novel strategy to improve the catalytic performance of heme analogs through ligand geometric modulation. 相似文献