The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

Effects of non-thermal plasma treating wheat kernel on the physicochemical properties of wheat flour and the quality of fresh wet noodles

The effects of non-thermal plasma (NTP) on the physicochemical properties of wheat flour and the quality of fresh wet noodles ( FWN) were investigated. The results showed that NTP effectively decreased the total plate count (TPC), yeast and mould count (YMC) and Bacillus spp. in wheat flour. Wet gluten contents and the stability time reached the maximum when treated for 20 s. The viscosity of starch increased significantly after treatment due to the increased of damaged starch. The contents of secondary structure were altered to some extent, which was because that the ordered network structure of gluten protein broken. Furthermore, compared with the control, texture properties of FWN were enhanced significantly at 20 s, and the darkening rate of FWN was greatly inhibited due to the low polyphenol oxidase (PPO) activity. Consequently, the most suitable treatment was 500 W for 20 s, providing a basis for the application of NTP in flour products.     

一起发电机定子接地故障的分析与处理

文章介绍了海外某大型火力发电厂发生的一起发电机定子接地故障的分析和处理过程,对发电厂类似故障的处理和海外发电厂的运行和维护提供了参考。     

Ir(III) and Ru(II) Complexes in Photoredox Catalysis and Photodynamic Therapy: A New Paradigm towards Anticancer Applications

Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment.     

Statistical Piezotronic Effect in Nanocrystal Bulk by Anisotropic Geometry Control

Utilizing inner-crystal piezoelectric polarization charges to control carrier transport across a metal-semiconductor or semiconductor–semiconductor interface, piezotronic effect has great potential applications in smart micro/nano-electromechanical system (MEMS/NEMS), human-machine interfacing, and nanorobotics. However, current research on piezotronics has mainly focused on systems with only one or rather limited interfaces. Here, the statistical piezotronic effect is reported in ZnO bulk composited of nanoplatelets, of which the strain/stress-induced piezo-potential at the crystals’ interfaces can effectively gate the electrical transport of ZnO bulk. It is a statistical phenomenon of piezotronic modification of large numbers of interfaces, and the crystal orientation of inner ZnO nanoplatelets strongly influence the transport property of ZnO bulk. With optimum preferred orientation of ZnO nanoplatelets, the bulk exhibits an increased conductivity with decreasing stress at a high pressure range of 200–400 MPa, which has not been observed previously in bulk. A maximum sensitivity of 1.149 µS m⁻¹ MPa⁻¹ and a corresponding gauge factor of 467–589 have been achieved. As a statistical phenomenon of many piezotronic interfaces modulation, the proposed statistical piezotronic effect extends the connotation of piezotronics and promotes its practical applications in intelligent sensing.     

Surface treatment of titanium dioxide nanopowder using rotary electrode dielectric barrier discharge reactor

Titanium dioxide (TiO2) nanopowder (P-25;Degussa AG) was treated using dielectric barrier discharge (DBD) in a rotary electrode DBD (RE-DBD) reactor.Its electrical and optical characteristics were investigated during RE-DBD generation.The treated TiO2 nanopowder properties and structures were analyzed using x-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR).After RE-DBD treatment,XRD measurements indicated that the anatase peak theta positions shifted from 25.3° to 25.1°,which can be attributed to the substitution of new functional groups in the TiO2 lattice.The FTIR results show that hydroxyl groups (OH) at 3400 cm-1 increased considerably.The mechanism used to modify the TiO2 nanopowder surface by air DBD treatment was confirmed from optical emission spectrum measurements.Reactive species,such as OH radical,ozone and atomic oxygen can play key roles in hydroxyl formation on the TiO2 nanopowder surface.