The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

用CPLD实现SRAM工艺FPGA的安全应用

提出了一种利用CPLD产生的伪随机码来加密SRAM工艺FPGA的方法,并详细介绍了具体的电路和VHDL代码。     

醇镁还原法一步制取对氯苯胺的研究

醇镁还原法一步制取对氯苯胺是一种新的方法 ,研究发现最佳反应温度为 80℃～ 85℃ ,反应时间为4h ,对氯硝基苯与镁粉的用量 (物质的量比 )为 1∶3,产率为 80 %。     

Biochemical mechanisms conferring cross-resistance to fumigant toxicities of essential oils in a chlorpyrifos-methyl resistant strain of Oryzaephilus surinamensis L. (Coleoptera: Silvanidae)

The fumigant toxicities of lavender and ylang-ylang essential oils were tested against a chlorpyrifos-methyl resistant strain (QVOS102) and an insecticide-susceptible reference strain (VOS48) of the saw-toothed grain beetle, Oryzaephilus surinamensis L. (Coleoptera: Silvanidae). The resistant strain showed 1.3- and 1.6-fold higher tolerance against lavender and ylang-ylang fumigation toxicity, respectively, relative to the susceptible strain. LT₅₀ values calculated as the time to attain 50% mortality of tested insects during fumigation were determined at two different concentrations. At 15 μl/l of air, QVOS102 had 2.9- and 1.4-fold higher LT₅₀ values for lavender and ylang-ylang fumigation toxicity, respectively, than VOS48. At 200 μl/l air, QVOS102 had 6.4- and 2.9-fold higher LT₅₀ values for lavender and ylang-ylang fumigation toxicity, respectively, than VOS48. Piperonyl butoxide, a potential inhibitor of cytochrome P450-dependent monooxygenase, increased fumigant toxicities of the two essential oils against QVOS102. The enhanced tolerance for the essential oil may have resulted from the enhancement of detoxifying enzymes associated with insecticide resistance.     

大颗粒尿素造粒工艺简介

介绍了大颗粒尿素造粒工艺，着重介绍了荷兰NSM公司的流化床造粒技术和法国K－T公司的流化床转鼓造粒（FDG）技术。     

直接氯化法合成对硝基氯化苄

介绍了以对硝基甲苯和氯气为原料 ,在催化剂存在下合成对硝基氯化苄的方法 ,考察了催化剂种类、反应温度、溶剂配比等因素对反应的影响 ,优化的反应条件为 :对硝基甲苯用量 1 3 7g,对硝基甲苯 /邻二氯苯 (摩尔比 ) =1∶ 0 .6,w (偶氮二异丁腈 ) =0 .6% ,反应时间 3 h,反应温度 1 60℃ ,产物单程收率大于 65 % ;将反应混合物中未反应的原料分离后 ,以无水乙醇为溶剂结晶纯化 ,物料 /溶剂 (摩尔比 ) =1∶ 1 .5时晶体含量在 99.0 %以上 ,结晶收率达 67     

A p‐version,first order shear deformation,finite element for geometrically non‐linear vibration of curved beams

A p‐version, hierarchical finite element for curved, moderately thick, elastic and isotropic beams is introduced. The convergence properties of the element are analysed and some results are compared with results published elsewhere or calculated using a commercial finite element package. It is verified that, with the proposed element, shear locking does not affect the computation of the natural frequencies and that low dimensional, accurate models are obtainable. Geometrically non‐linear vibrations due to finite deformations, which occur for harmonic excitations with frequencies close to the first three natural frequencies of vibration, are investigated using Newmark's method. The influence of the thickness, longitudinal inertia and curvature radius on the dynamic behaviour of curved beams are studied. Copyright © 2004 John Wiley & Sons, Ltd.