Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Synthesis of ZnO nanospheres with uniform nanopores by a hydrothermal process

ZnO nanospheres were successfully synthesized by a hydrothermal process (S1 sample) and a wet-chemical method (S2 sample). Following synthesis, calcination treatment at 450 °C was performed for the sample prepared by the wet-chemical method (S3 sample). All of the samples possessed a regular spherical shape. A polycrystalline wurtzite structure was confirmed in the S1 and S3 samples by X-ray diffraction and selected area electron diffraction, whereas a mixture of ZnO nanoparticles and amorphous materials was observed in the sample S2. The surface area and pore structure of the samples were investigated by nitrogen adsorption–desorption measurements. Uniform nanopores with a diameter of 4.07 nm were present in the S1 sample while a broad pore size distribution was obtained for the S2 and S3 samples. The highest surface area was obtained for the S1 sample and a possible formation mechanism was studied.     

Formation of p-type ZnO film on InP substrate by phosphor doping

ZnO thin film was initially deposited on InP substrate by radio frequency (rf) magnetron sputtering and the diffusion process was performed using the closed ampoule technique where Zn₃P₂ was used as the dopant source. To verify the junction formation of ZnO thin films, the electrical properties were measured, and the effects of Zn₃P₂ diffusion on ZnO thin films were investigated. It is observed that the electrical property of the film is changed from n-type to p-type by dopant diffusion effect. Based on the results, it is confirmed that ZnO thin films can be a potential candidate for ultraviolet (UV) optical devices.     

Preparation of Ga-doped ZnO films by pulsed dc magnetron sputtering with cylindrical rotating target for thin film solar cell applications

Applicability of Ga-doped ZnO (GZO) films for thin film solar cells (TFSCs) was investigated by preparing GZO films via pulsed dc magnetron sputtering (PDMS) with rotating target. The GZO films showed improved crystallinity and increasing degree of Ga doping with increasing thickness to a limit of 1000 nm. The films also fulfilled requirements for the transparent electrodes of TFSCs in terms of electrical and optical properties. Moreover, the films exhibited good texturing potential based on etching studies with diluted HCl, which yielded an improved light trapping capability without significant degradation in electrical propreties. It is therefore suggested that the surface-textured GZO films prepared via PDMS and etching are promising candidates for indium-free transparent electrodes for TFSCs.     

Sidewall-insert compound based on ZnO-treated aramid pulp fibers for run-flat tires

Abstract

To improve the endurance performance of run-flat tires by preventing the sidewall from folding at zero air pressure, a master batch of natural rubber and ZnO-treated aramid pulp (AP) is applied to the rubber sidewall-insert-layer compound. The mechanical, viscoelastic, and fatigue properties of the compounds are investigated by varying the AP content, and the endurance performance of actual run-flat tires is assessed. The results indicate that the mechanical properties are improved and the hysteresis is reduced as the AP content increased. The overall trend of the endurance times of the run-flat tires is consistent with the results of the DeMattia tests, constant-strain fatigue tests, and high-temperature tensile tests. The run-flat endurance time of the tire containing one part per hundred rubber (phr) of AP is superior to that of the tire containing 3 phr of AP because of the enhanced dispersion of the AP fibers.     

Different ocular dominance map formation influenced by orientation preference columns in visual cortices

In animal experiments, the observed orientation preference and ocular dominance columns in the visual cortex of the brain show various pattern types. Here, we show that the different visual map formations in various species are due to the crossover behavior in anisotropic systems composed of orientational and scalar components such as easy-plane Heisenberg models. We predict the transition boundary between different pattern types with the anisotropy as a main bifurcation parameter, which is consistent with experimental observations.     

Hydrophobic Shielding of Outer Surface: Enhancing the Chemical Stability of Metal–Organic Polyhedra

Metal–organic polyhedra (MOP) are a promising class of crystalline porous materials with multifarious potential applications. Although MOPs and metal–organic frameworks (MOFs) have similar potential in terms of their intrinsic porosities and physicochemical properties, the exploitation of carboxylate MOPs is still rudimentary because of the lack of systematic development addressing their chemical stability. Herein we describe the fabrication of chemically robust carboxylate MOPs via outer‐surface functionalization as an a priori methodology, to stabilize those MOPs system where metal–ligand bond is not so strong. Fine‐tuning of hydrophobic shielding is key to attaining chemical inertness with retention of the framework integrity over a wide range of pH values, in strong acidic conditions, and in oxidizing and reducing media. These results are further corroborated by molecular modelling studies. Owing to the unprecedented transition from instability to a chemically ultra‐stable regime using a rapid ambient‐temperature gram‐scale synthesis (within seconds), a prototype strategy towards chemically stable MOPs is reported.     

Observable Structures of Small Neutral and Anionic Gold Clusters

Since gold clusters have mostly been studied theoretically by using DFT calculations, more accurate studies are of importance. Thus, small neutral and anionic gold clusters (Au_n and Au_n^?, n=4–7) were investigated by means of coupled cluster with singles, doubles, and perturbative triple excitations [CCSD(T)] calculations with large basis sets, and some differences between DFT and CCSD(T) results are discussed. Interesting isomeric structures that have dangling atoms were obtained. Structures having dangling atoms appear to be stable up to n=4 for neutral gold clusters and up to n=7 for anionic clusters. The relative stabilities and electronic properties of some isomers and major structures are discussed on the basis of the CCSD(T) calculations. This accurate structure prediction of small gold clusters corresponding to experimental photoelectron spectral peaks is valuable in the field of atom‐scale materials science including nanocatalysts.     

Effect of Penetration Enhancers on Toenail Delivery of Efinaconazole from Hydroalcoholic Preparations

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.