Inhibitor selectivity between aldo–keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111)

AbstractThe antineoplastic target aldo–keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an “AKR1B1-like” active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation

CsI:Tl^+,Yb^(2+): ultra-high light yield scintillator with reduced afterglow

The afterglow problem has been preventing CsI:Tl single crystal scintillators from being used for applications in the field of computer tomography and high-speed imaging. We show that Yb^(2+) codoping in CsI:Tl can reduce it at least by one order of magnitude after 50 ms from X-ray cut-off compared to ordinary CsI:Tl. After optimization of the Yb^(2+) and Tl^+ concentrations, the doubly doped CsI:Tl,Yb crystal exhibits an ultra-high light yield of 90 000 ± 6000 photons MeV^(−1), energy resolution 7.9%@511 keV and low afterglow level of about 0.035% at 80 ms. Simultaneous improvement in afterglow, light yield and energy resolution in CsI:Tl-based scintillators paves the way to its application in computer tomography and high-speed imaging. The physical mechanism and role of ytterbium ions in afterglow suppression are proposed

Research on Overhead Line Cost Prediction Based on Index Construction

In order to meet the growing demand of the society for electric power, the construction of electric power infrastructure is constantly carried out. However, investment in construction and cost control are particularly important. Because of its own characteristics, overhead line project cost control management is difficult to carry out. According to the characteristics of overhead line engineering, this paper constructs an overhead line engineering cost index system composed of 24 indexes including voltage grade from three aspects: technical conditions, engineering quantity attribute and cost attribute. Combining with the actual data of the completed project, the BP neural network algorithm is used to predict the static investment of the project. The accuracy of the prediction model reaches 99.9%. This verifies the rationality and comprehensiveness of the overhead line project cost index system constructed in this paper, and provides reliable guidance for the overhead line project cost management

Theoretical Prediction and Experimental Validation of the Glass-Forming Ability and Magnetic Properties of Fe-Si-B Metallic Glasses from Atomic Structures

Developing new soft magnetic amorphous alloys with a low cost and high saturation magnetization (Bs) in a simple alloy system has attracted substantial attention for industrialization and commercialization. Herein, the glass-forming ability (GFA), thermodynamic properties, soft magnetic properties, and atomic structures of Fe80+xSi5−xB15 (x = 0–4) amorphous soft magnetic alloys were investigated by ab initio molecular dynamics (AIMD) simulations and experiments. The pair distribution function (PDF), Voronoi polyhedron (VP), coordination number (CN), and chemical short- range order (CSRO) were analyzed based on the AIMD simulations for elucidating the correlations between the atomic structures with the glass-forming ability and magnetic properties. For the studied compositions, the Fe82Si3B15 amorphous alloy was found to exhibit the strongest solute–solute avoidance effect, the longest Fe-Fe bond, a relatively high partial CN for the Fe-Fe pair, and the most pronounced tendency to form more stable clusters. The simulation results indicated that Fe82Si3B15 was the optimum composition balancing the saturation magnetization and the GFA. This prediction was confirmed by experimental observations. The presented work provides a reference for synthesizing new Fe-Si-B magnetic amorphous alloys

Effect of Allicin against Ischemia/Hypoxia-Induced H9c2 Myoblast Apoptosis via eNOS/NO Pathway-Mediated Antioxidant Activity

Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) is the main biologically active ingredient in garlic. The present study investigated the protective effect of allicin against cardiomyocyte apoptosis that was induced by ischemia in vitro and the potential molecular mechanisms that were involved in this antiapoptotic effect. The results indicated that allicin increased H9c2 cell activity and attenuated the rate of apoptosis that was induced by ischemia/hypoxia. Intracellular calcium concentrations significantly decreased in the allicin-treated groups. Bax expression significantly decreased, and Bcl-2 expression increased in allicin-treated rats. Nitric oxide blockade significantly inhibited these effects. Allicin also increased the activity of SOD and NO release and decreased MDA levels. Allicin significantly increased the expression of eNOS, Nrf2, and HO-1 proteins. Collectively, these findings demonstrate that allicin protects H9c2 cells against apoptosis, and this protective effect appears to occur via eNOS/NO pathway-mediated antioxidant activity