Design, synthesis, and biological evaluation of 3-phenyl substituted pyridine derivatives as potential dual inhibitors of XOR and URAT1.

Xanthine oxidoreductase (XOR) and uric acid transporter 1 (URAT1) are two most widely studied targets involved in production and reabsorption of uric acid, respectively. Marketed drugs almost target XOR or URAT1, but sometimes, single agents might not achieve aim of lowering uric acid to ideal value in clinic. Thus, therapeutic strategies of combining XOR inhibitors with uricosuric drugs were proposed and implemented. Based on our initial work of virtual screening, A and B were potential hits for dual-targeted inhibitors on XOR/URAT1. By docking A/B with XOR/URAT1 respectively, compounds I1-7 were designed to get different degree of inhibition effect on XOR and URAT1, and I7 showed the best inhibitory effect on XOR (IC50 = 0.037 ± 0.001 µM) and URAT1 (IC50 = 546.70 ± 32.60 µM). Further docking research on I7 with XOR/URAT1 led to the design of compounds II with the significantly improved inhibitory activity on XOR and URAT1, such as II11 and II15. Especially, for II15, the IC50 of XOR is 0.006 ± 0.000 µM, superior to that of febuxostat (IC50 = 0.008 ± 0.000 µM), IC50 of URAT1 is 12.90 ± 2.30 µM, superior to that of benzbromarone (IC50 = 27.04 ± 2.55 µM). In acute hyperuricemia mouse model, II15 showed significant uric acid lowering effect. The results suggest that II15 had good inhibitory effect on XOR/URAT1, with the possibility for further investigation in in-vivo models of hyperuricemia.

Porous NiMoO4 Nanosheet Films and a Device with Ultralarge Optical Modulation for Electrochromic Energy-Storage Applications.

Reducing building energy consumption, improving aesthetics, and improving occupant privacy as well as comfort by dynamically adjusting solar radiation are important application areas for electrochromic (EC) smart windows. However, the current transition metal oxides still cannot meet the requirements of neutral coloration and large optical modulation. We report NiMoO4 nanosheet films directly grown on fluorine-doped tin oxide glasses. The as-grown NiMoO4 film not only achieves neutral coloration from transparent to dark brown but also shows an ultralarge optical modulation (86.8% at 480 nm) and excellent cycling stability (99.4% retention of maximum optical modulation after 1500 cycles). Meanwhile, an EC device demonstrating good EC performance was constructed. These results will greatly promote the research and development of binary transition metal oxides for both EC and energy-storage applications, and NiMoO4 films may be an excellent candidate to replace NiO films as ion-storage layers in complementary EC devices with WO3 films as EC layers.

Multifunctional carbon dots for glutathione detection and Golgi imaging.

Glutathione (GSH) is present in almost every cell in the body and plays various integral roles in many biological processes. The Golgi apparatus is a eukaryotic organelle for the biosynthesis, intracellular distribution, and secretion of various macromolecules; however, the mechanism of GSH in the Golgi apparatus has not been fully elucidated. Here, specific and sensitive sulfur-nitrogen co-doped carbon dots (SNCDs) with orange-red fluorescence was synthesized for the detection of GSH in the Golgi apparatus. The SNCDs have a Stokes shift of 147 nm and excellent fluorescence stability, and they exhibited excellent selectivity and high sensitivity to GSH. The linear response of the SNCDs to GSH was in the range of 10-460 µM (LOD = 0.25 µΜ). More importantly, we used SNCDs with excellent optical properties and low cytotoxicity as probes, and successfully realized golgi imaging in HeLa cells and GSH detection at the same time.

Nitrogen-doped carbon dots with high selectivity for hydrosulfide sensing and their living cells imaging.

Hydrosulfuric acid is an aqueous solution of hydrogen sulfide (H2S). At physiological pH, approximately 80% of the total amount of H2S exists in the form of monoanionic HS-. Because HS- is both widely distributed and highly toxic to humans, it is necessary to design an efficient method to detect HS- with high sensitivity and selectivity. So, the nitrogen-doped carbon dots (NCDs) with green fluorescence are synthesized using a one-step hydrothermal method. The as-prepared NCDs show it can be effectively used as an indicator for monitoring HS-. And the NCD fluorescence intensity exhibits a linear relationship with HS- concentration. In addition, NCDs as a probe can be applied for fluorescence imaging in living cells to detect the presence of trace exogenous HS-.

Cd-free InP/ZnSeS quantum dots for ultrahigh-resolution imaging of stimulated emission depletion.

Stimulated emission depletion (STED) nanoscopy is a promising super-resolution imaging technique for microstructure imaging; however, the performance of super-resolution techniques critically depends on the properties of the fluorophores (photostable fluorophores) used. In this study, a suitable probe for improving the resolution of STED nanoscopy was investigated. Quantum dots (QDs) typically exhibit good photobleaching resistance characteristics. In comparison with CdSe@ZnS QDs and CsPbBr3 QDs, Cd-free InP/ZnSeS QDs have a smaller size and exhibit an improved photobleaching resistance. Through imaging using InP/ZnSeS QDs, we achieved an ultrahigh resolution of 26.1 nm. Furthermore, we achieved a 31 nm resolution in cell experiments involving InP/ZnSeS QDs. These results indicate that Cd-free InP/ZnSeS QDs have significant potential for application in fluorescent probes for STED nanoscopy.

Noval Dual-Emission Fluorescence Carbon Dots as a Ratiometric Probe for Cu2+ and ClO- Detection.

The use of carbon dots (CDs) with dual emission based on ratiometric fluorescence has been attracting attention in recent times for more accurate ion detection since they help avoid interference from background noise, probe concentration, and complexity. Herein, novel dual-emission nitrogen-doped CDs (NCDs) were prepared by a simple method for Cu2+ and ClO- detection. The NCDs showed excellent anti-interference ability and selectivity for different emissions. In addition, a good linear relationship was observed between the fluorescence intensity (FI) of the NCD solutions in different emissions with Cu2+ (0-90 µM) and ClO- (0-75 µM). The limits of both Cu2+ detection and ClO- were very low, at 17.7 and 11.6 nM, respectively. The NCDs developed herein also showed a good recovery rate in water for Cu2+ and ClO- detection. Hence, they are expected to have a more extensive application prospect in real samples.

Advantageous Interfacial Effects of AgPd/g-C3 N4 for Photocatalytic Hydrogen Evolution: Electronic Structure and H2 O Dissociation.

Bimetallic AgPd nanoparticles have been synthesized before, but the interfacial electronic effects of AgPd on the photocatalytic performance have been investigated less. In this work, the results of hydrogen evolution suggest that the bimetallic AgPd/g-C3 N4 sample has superior activity to Ag/g-C3 N4 and Pd/g-C3 N4 photocatalysts. The UV/Vis diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, CO adsorption diffuse reflectance FTIR spectroscopy, and FTIR results demonstrate that in the AgPd/g-C3 N4 , the surface electronic structures of Pd and Ag are changed, which is beneficial for faster photogenerated electron transfer and greater H2 O molecule adsorption. In situ ESR spectra suggest that, under visible light irradiation, there is more H2 O dissociation to radical species on the AgPd/g-C3 N4 photocatalyst. Furthermore, DFT calculations confirm the interfacial electronic effects of AgPd/g-C3 N4 , that is, Pdδ- ⋅⋅⋅Agδ+ , and the activation energy of H2 O molecule dissociation on AgPd/g-C3 N4 is the lowest, which is the main contributor to the enhanced photocatalytic H2 evolution.