Search

High‐throughput drug discovery is highly dependent on the targets available to accelerate the process of candidate screening. Unbiased drug target identification is of crucial importance to reveal the mechanisms of protein–drug interactions. In recent years, energetics‐based protein conformation methods have become an alternative strategy for protein target discovery of bioactive drugs. In this study, we present a novel tannin protein precipitation method (TAP) for identifying target proteins of small molecules using the effect on protein solubility of tannin. The feasibility of this method was validated using a drug model of methotrexate. It was found that the known target DHFR yields a significant solubility shift. This method was further investigated with Annexin A2, the target protein of protopanaxadiol (PPD)‐S by western blot, and by screening potential target proteins of PPD‐S in K562 cells by quantitative proteomics. Finally, the TAP method was employed to differentiate the target proteins of pair chiral molecules PPD‐S and PPD‐R, which can bring up novel insights into the mechanism of drug–protein interactions. This study not only provides an effective tool for drug research and development but also offers new ideas for understanding the mechanism of action of natural chiral bioactive compounds. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and a major cause of cancer-related mortality worldwide. Small extracellular vesicles (sEVs) are heterogeneous populations of membrane-structured vesicles that can be found in many biological fluids and are currently considered as a potential source of disease-associated biomarkers for diagnosis. The purpose of this study was to define the proteomic and phosphoproteomic landscape of urinary sEVs in patients with HCC. Mass spectrometry-based methods were used to detect the global proteome and phosphoproteome profiles of sEVs isolated by differential ultracentrifugation. Label-free quantitation analysis showed that 348 differentially expressed proteins (DEPs) and 548 differentially expressed phosphoproteins (DEPPs) were identified in the HCC group. Among them, multiple phosphoproteins related to HCC, including HSP90AA1, IQGAP1, MTOR, and PRKCA, were shown to be upregulated in the HCC group. Pathway enrichment analysis indicated that the upregulated DEPPs participate in the regulation of autophagy, proteoglycans in cancer, and the MAPK/mTOR/Rap1 signaling pathway. Furthermore, kinase–substrate enrichment analysis revealed activation of MTOR, AKT1, MAP2Ks, and MAPKs family kinases in HCC-derived sEVs, indicating that dysregulation of the MAPK and mTOR signaling pathways may be the primary sEV-mediated molecular mechanisms involved in the development and progression of HCC. This study demonstrated that urinary sEVs are enriched in proteomic and phosphoproteomic signatures that could be further explored for their potential use in early HCC diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

A series of bimetallic NixCuy catalysts with different metal molar ratios, supported on nitric acid modified rice husk-based porous carbon (RHPC), were prepared using a simple impregnation method for the liquid-phase hydrogenation of furfural (FFA) to tetrahydrofurfuryl alcohol (THFA). The Ni2Cu1/RHPC catalyst, with an average metal particle size of 9.3 nm, exhibits excellent catalytic performance for the selective hydrogenation of FFA to THFA. The 100% conversion of FFA and the 99% selectivity to THFA were obtained under mild reaction conditions (50 °C, 1 MPa, 1 h), using water as a green reaction solvent. The synergistic effect of NiCu alloy ensures the high catalytic activity. The acid sites and oxygen-containing functional groups on the surface of the modified RHPC can enhance the selectivity of THFA. The Ni2Cu1/RHPC catalyst offers good cyclability and regenerability. The current work proposes a simple method for preparing an NiCu bimetallic catalyst. The catalyst exhibits excellent performance in the catalytic hydrogenation of furfural to tetrahydrofurfuryl alcohol, which broadens the application of non-noble metal bimetallic nanocatalysts in the catalytic hydrogenation of furfural. [ABSTRACT FROM AUTHOR]

Objectives. It is a high risk for adolescents with first-episode major depressive disorder (MDD) to commit suicide. However, few studies reported the effect of modified electroconvulsive therapy (MECT) in first-episode antipsychotic-naive MDD adolescents. Methods. The study explores the alternations of regional homogeneity of modified electroconvulsive therapy to treat the first-episode antipsychotic-naive major depressive disorder. 72 first-episode MDD patients were recruited from Tianyou Hospital Affiliated to Wuhan University of Science and Technology from October 2017 to May 2020, and 65 of 72 completed the trial. Results. Before MECT treatment, ReHo values of the bilateral cerebellum and left cuneus were higher, and ReHo value of left postcentral and supramarginal gyrus was lower in MDD patients compared to healthy subjects (HS). After treatment, the MDD patients have higher ReHo values of the right insula and postcentral gyrus, while left fusiform gyrus were lower than the pretreatment. Compared to the HS, the ReHo values of left lingual gyrus, right calcarine cortex, and right mid occipital thalamus were higher in the posttreatment. In the posttreatment, left calcarine cortex and right cerebrum were lower than in healthy subjects. Conclusions. The study confirmed that MECT improves psychotic symptoms in patients with first-episode antipsychotic-naive MDD. These results further contributed to a more tailored treatment approach to MDD from the pathophysiological and neuroimaging views. [ABSTRACT FROM AUTHOR]