A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir

oseltamivir 的使用，广泛地是的 stockpiled 为在可能的鸟的流行性感冒的使用的药之一流行，被报导了与 neuropsychiatricdisorders 和严重皮肤反应被联系，首先在日本。这里，我们在 dbSNP 数据库识别了非同义的 SNP (单个核苷酸多型性) ， R41Q 在 humancytosolic sialidase 的酶的活跃地点附近，是 oseltamivir 的目标的病毒 neuraminidase 的一个相当或相同事物。在欧洲、非洲的美国人口的 9.29% 亚洲人口和没有的这 SNPoccurred。Ourstructural 分析和 Ki 大小使用试管内 sialidase 试金显示这 SNPcould 增加人的 sialidase 的非计划中的有约束力的亲密关系到 oseltamivir 羧化物， oseltamivir 的活跃形式，因此减少 sialidase 活动。另外，这 SNP 自己与一项内在地更低的 sialidase 活动导致酶，由它的增加的 Km 证明 Vmax 珍视并且减少。理论上，到有这 SNP 的人的 oseltamivir 的管理可能进一步减少他们的 sialidase 活动。我们注意 oseltamivir 的 reportedneuropsychiatric 副酌和人的 sialidase-relateddisorders 的已知的症状的类似。我们建议这个充实亚洲人的 sialidase 变化由 SNP 引起了，在同型结合的形式可能，可以与对 oseltamivir 的某些严重不利反应被联系。

Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion(I/R) injury.METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzymelinked immunosorbent assay(ELISA). The serum levels of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase d UTP nick end labeling assay. The production of malondialdehyde(MDA) and superoxide dismutase(SOD) and villous injury scores were also measured.RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines,including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase(AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1(HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway.

Effects of laser shock processing,solid solution and aging,and cryogenic treatments on microstructure and thermal fatigue performance of ZCuAl_(10)Fe_(3)Mn_(2)alloy

The materials used in variable temperature conditions are required to have excellent thermal fatigue performance.The effects of laser shock processing(LSP),solid solution and aging treatment(T6),and cryogenic treatment(CT)on both microstructure and thermal fatigue performance of ZCuAl_(10)Fe_(3)Mn_(2) alloys were studied.Microstructure and crack morphology were then examined by scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDS).The result showed that,after being subjected to the combination treatment of T6+CT+LSP,the optimal mechanical properties and thermal fatigue performance were obtained for the ZCuAl_(10)Fe_(3)Mn_(2) alloy with the tensile strength,hardness,and elongation of 720 MPa,300.16 HB,and 16%,respectively,and the thermal fatigue life could reach 7,100 cycles when the crack length was 0.1 mm.Moreover,the ZCuAl_(10)Fe_(3)Mn_(2) after combination treatment shows high resistance to oxidation,good adhesion between the matrix and grain boundaries,and dramatically reduced growth rate of crack.During thermal fatigue testing,under the combined action of thermal and alternating stresses,the microstructure around the sample notch oxidized and became loose and porous,which then converted to micro-cracks.Fatigue crack expanded along the grain boundary in the early stage.In the later stage,under the cyclic stress accumulation,the oxidized microstructure separated from the matrix,and the fatigue crack expanded in both intergranular and transgranular ways.The main crack was thick,and the path was meandering.

Development of a triple channel detection probe for hydrogen peroxide

The rapid and reliable measurement of hydrogen peroxide（H_2O_2） is imperative for many areas of technology, including pharmaceutical, clinical, food industry and environmental applications. In this work, a novel multifunctional complex, [Ru（bpy）_2（luminol-bpy）]（PF_6）_2（bpy： 2,20-bipyridine）, was designed and synthesized by incorporating a Ru（II） complex with a luminal group. In the presence of horseradish peroxidase（HRP）, reaction of [Ru（bpy）_2（luminol-bpy）]_2＋with H_2O_2 can be monitored by three sensing channels including photoluminescence（PL）, chemiluminiscence（CL） and eletrochemiluminiscence（ECL）. The quantitative assays for H_2O_2 in aqueous solutions using [Ru（bpy）_2（Luminalbpy）]（PF_6）_2as a probe were established with PL, ECL and CL signal output modes, respectively.