VI-116, A Novel Potent Inhibitor of VRAC with Minimal Effect on ANO1

Volume-regulated anion channel (VRAC) is ubiquitously expressed and plays a pivotal role in vertebrate cell volume regulation. A heterologous complex of leucine-rich repeat containing 8A (LRRC8A) and LRRC8B-E constitutes the VRAC, which is involved in various processes such as cell proliferation, migration, differentiation, intercellular communication, and apoptosis. However, the lack of a potent and selective inhibitor of VRAC limits VRAC-related physiological and pathophysiological studies, and most previous VRAC inhibitors strongly blocked the calcium-activated chloride channel, anoctamin 1 (ANO1). In the present study, we performed a cell-based screening for the identification of potent and selective VRAC inhibitors. Screening of 55,000 drug-like small-molecules and subsequent chemical modification revealed 3,3′-((2-hydroxy-3-methoxyphenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) (VI-116), a novel potent inhibitor of VRAC. VI-116 fully inhibited VRAC-mediated I⁻ quenching with an IC₅₀ of 1.27 ± 0.18 μM in LN215 cells and potently blocked endogenous VRAC activity in PC3, HT29 and HeLa cells in a dose-dependent manner. Notably, VI-116 had no effect on intracellular calcium signaling up to 10 μM, which completely inhibited VRAC, and showed high selectivity for VRAC compared to ANO1 and ANO2. However, DCPIB, a VRAC inhibitor, significantly affected ATP-induced increases in intracellular calcium levels and Eact-induced ANO1 activation. In addition, VI-116 showed minimal effect on hERG K⁺ channel activity up to 10 μM. These results indicate that VI-116 is a potent and selective VRAC inhibitor and a useful research tool for pharmacological dissection of VRAC.     

Two additional cases of metformin‐associated encephalopathy in patients with end‐stage renal disease undergoing hemodialysis

We report on two additional cases of metformin‐associated encephalopathy in patients with end‐stage renal disease (ESRD) undergoing hemodialysis. Two patients were seen at our hospital with abnormal neurological signs and symptoms. Magnetic resonance imaging (MRI) revealed the same pattern of high signal intensity in both basal ganglia in T2‐weighted images in the two patients. The two patients had started taking metformin 5 and 6 weeks earlier at the same dose of 1000 mg per day. Metformin was immediately stopped, and regular hemodialysis was conducted. Their signs and symptoms resolved completely after these measures. The high signal intensity in both ganglia in T2‐weighted MRI also disappeared. We should suspect metformin‐induced encephalopathy and withdraw the drug when presented with diabetic patients with chronic kidney disease and neurological signs and symptoms of unknown cause.     

Effective suppression of deactivation by utilizing Ni-doped ordered mesoporous alumina-supported catalysts for the production of hydrogen and CO gas mixture from methane

Several different kinds of ordered mesoporous alumina (OMA)-supported and Ni-doped OMA-supported Ni catalysts have been prepared for catalytic partial oxidation of methane (CPOM) to produce hydrogen and CO gas mixture. The Ni metal was incorporated in various ways of the impregnation, the doping, and the partial doping followed by impregnation. The prepared OMA-supported catalysts showed a wormhole-like, pseudo-hexagonal structure. By incorporating Ni in the OMA matrix during synthesis of supports, the resulting catalysts showed better-distributed and less-sintered nanocrystals even after CPOM at elevated temperature for over 100 h. By employing the partial doping of Ni followed by impregnation of Ni, the prepared CPOM catalyst was found more productive due to the well-distributed and well-anchored Ni nanocrystals inside the OMA matrix and the confined ordered mesopores as well. Through the test under non-stoichiometric feed ratio, the catalyst prepared only by impregnation was found vulnerable to carbon deposition and deactivated more rapidly. Even worse, the formation rate of carbon deposition was so fast that the test could not be conducted due to the increased pressure difference. In contrast, the highly distributed Ni nanocrystals partially or fully utilizing doping were found to have stronger resistance to carbon deposition.     

Assessment of printability for printed electronics patterns by measuring geometric dimensions and defining assessment parameters

The printability of patterns for printed electronic devices determines the performance, yield rate, and reliability of the devices; therefore, it should be assessed quantitatively. In this paper, parameters for printability assessment of printed patterns for width, pinholes, and edge waviness are suggested. For quantitative printability assessment, printability grades for each parameter are proposed according to the parameter values. As examples of printability assessment, printed line patterns and mesh patterns obtained using roll-to-roll gravure printing are used. Both single-line patterns and mesh patterns show different levels of printability, even in samples obtained using the same printing equipment and conditions. Therefore, for reliable assessment, it is necessary to assess the printability of the patterns by enlarging the sampling area and increasing the number of samples. We can predict the performance of printed electronic devices by assessing the printability of the patterns that constitute them.

     

Die quenching limit of AA2024 aluminum alloy billet on servo press

Die quenching of AA2024 aluminum alloy billets was carried out on a servo press with ram-motion control of WC-20 mass%Co dies directly after solution heat treatment (SHT). To clarify the dependence on billet size for die quenching, two billets with a height of h₀ = 8 mm or 16 mm and with the same diameter of 16 mm were prepared. The cylindrical billets were heated in an electric furnace at 823 K and transferred to the press. Then the billets were uniaxially compressed with a reduction in height (Δh/h₀) of 2% or 5%, and further held between the dies. The sandwiching duration by dies (t_d.q.) was varied from 0 to 8 s. Based a measured temperature change, hardness and TG–DTA analysis, it is found that die quenching is successfully carried out without precipitation hardening only in the case of the billet with a height of 8 mm and t_d.q. > 6 s. The reduction in height is limited less than 5% by intergranular fracture on side surface of billet during the die quenching process.     

Anti-diabetic effects of mulberry (Morus alba L.) branches and oxyresveratrol in streptozotocin-induced diabetic mice

Food Science and Biotechnology - Despite with accumulating evidences on the anti-diabetic effects of mulberry branch (MB), the major active component for the activity has not been known. Oral...     

Numerical simulation of gas-assisted polymer-melt electrospinning: Parametric study of a multinozzle system for mass production

In this study, we developed a multiphysics model for simulation of a gas-assisted melt-electrospinning (GAME) process, focusing on jet formation and propagation behavior. By numerically calculating the stresses acting on the jet during a single-nozzle GAME process, the shear viscous stress was identified as the main factor with respect to jet stretch; thus, the relationship between shear viscous stress and jet thickness was investigated. The jet stretch ratio increased sharply when shear viscous stress reached the level at which jet sharpening occurred, leading to stable jet formation. We defined this stress as the critical shear viscous stress to determine stable spinnability. By imposing an electric field distribution calculated for a multi-nozzle array (number of nozzles, tip-to-tip distance, and applied voltage) on the boundary condition of the single-nozzle GAME simulation model, multinozzle GAME was simulated; this enabled proposal of a spinnability diagram for stable spinning.     

Recent Progress of Fiber Shaped Lighting Devices for Smart Display Applications—A Fibertronic Perspective

Advances in material science and nanotechnology have fostered the miniaturization of devices. Over the past two decades, the form-factor of these devices has evolved from 3D rigid, volumetric devices through 2D film-based flexible electronics, finally to 1D fiber electronics (fibertronics). In this regard, fibertronic strategies toward wearable applications (e.g., electronic textiles (e-textiles)) have attracted considerable attention thanks to their capability to impart various functions into textiles with retaining textiles' intrinsic properties as well as imperceptible irritation by foreign matters. In recent years, extensive research has been carried out to develop various functional devices in the fiber form. Among various features, lighting and display features are the highly desirable functions in wearable electronics. This article discusses the recent progress of materials, architectural designs, and new fabrication technologies of fiber-shaped lighting devices and the current challenges corresponding to each device's operating mechanism. Moreover, opportunities and applications that the revolutionary convergence between the state-of-the-art fibertronic technology and age-long textile industry will bring in the future are also discussed.