Involvement of CHRNA6 in the Immune Response in Lung Squamous Cell Carcinoma and its Potential as a Drug Target for the Disease.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer with a poor prognosis and limited treatment options. Previous studies show that some components of the cholinergic pathway may play important roles in the tumorigenesis of lung cancer, including LUSC. OBJECTIVE: The purpose of this study is to investigate the involvement of cholinergic genes in immune infiltration in LUSC, and identify the key genes in the pathway and analyze their potential as targets for LUSC treatment and novel drugs. METHODS: We first screened the cholinergic genes associated with immune infiltration in LUSC based on transcriptomic samples and explored the correlation between the key genes and immune infiltrating cells and immune pathways. Then, we assessed the effect of immunotherapeutic response in the high and low-expression groups of key genes in vitro. And finally, we screened potential drugs for the treatment of LUSC. RESULTS: We found that the expression of CHRNA6, the gene encoding the α6 subunit of nicotinic acetylcholine receptors (nAChR), was significantly correlated with the proportion of immune infiltrating cells in LUSC, and the high expression level of the gene was associated with poor prognosis of the disease. Also, the proportion of Tregs, M1 macrophages, and resting mast cells was correlated with the expression of CHRNA6. In addition, LUSC patients with higher CHRNA6 expression levels had better immunotherapy responses. Furthermore, we found that the drugs, i.e., adavosertib, varbulin and pyrazoloacridine, had a strong affinity with CHRNA6, with adavosertib binding most stably with the protein. CONCLUSION: CHRNA6 may be associated with immune infiltration in LUSC and affects patient prognosis and immunotherapeutic response by regulating immune cells and immune pathways. In addition, adavosertib may be a potential drug for the treatment of LUSC.

Computational assessment of herbal medicine-derived compounds as potential inhibitors of SARS-CoV-2 main protease.

Since the main protease (Mpro) is crucial for the COVID-19 virus replication and transcription, searching for Mpro inhibitors is one possible treatment option. In our study, 258 small molecules were collected from lung-related herbal medicines, and their structures were optimized with the B3LYP-D3/6-31G* method. After the molecular docking with Mpro, we selected the top 20 compounds for the further geometry optimization with the larger basis sets. After the further molecular docking, the top eight compounds were screened out. Then we performed molecular dynamics simulations and binding free energy calculations to determine stability of the complexes. Our results show that mulberrofuran G, Xambioona, and kuwanon D can bind Mpro well. In quantum chemistry studies, such as ESP and CDFT analyses, the compounds properties are predicted. Additionally, the drug-likeness analyses and ADME studies on these three candidate compounds verified that all of them conform to Libinski's rule and may be drug-like compounds.

Photocatalytic-induced bubble-propelled isotropic g-C3N4-coated carbon microsphere micromotors for dynamic removal of organic pollutants.

An isotropic bubble-propelled graphitic carbon nitride coated carbon microsphere (g-C3N4@CMS) micromotor that displays efficient self-propulsion powered by visible light irradiation and offers effective dynamic removal of organic pollutants for environmental applications is described. Its morphology, structure, and composition were systematically characterized, confirming the successful coating of g-C3N4 on the CMS surface and a core-shell structure. The photocatalytic-induced bubble propulsion of g-C3N4@CMS micromotors essentially stems from the asymmetrical photocatalytic redox reactions of g-C3N4 on the symmetrical surface of micromotors under visible light illumination. The stacking effect of g-C3N4 on the CMS surface results in a microporous structure that provides a highly reactive photocatalytic layer, which also leads to effective bubble evolution and propulsion at remarkable speeds of over 167.97 µm s-1 under 250 mW cm-2 visible light in the presence of 30% H2O2 fuel. The velocity can be easily and effectively adjusted by H2O2 fuel and the intensity of visible light. Furthermore, the motion state can be reversibly and wirelessly controlled by "switching on/off" light. Such coupling of the high photocatalytic activity of the porous g-C3N4 shell with the rapid movement of these light-driven micromotors, along with the corresponding fluid dynamics and mixing, result in greatly accelerated organic pollutant degradation. The adsorption kinetics have also been investigated and shown to follow pseudo-second-order kinetics. The strategy proposed here would inspire the designing of light-driven symmetrical micromotors because of the low cost, single component, and simple structure as well as facile and large-scale fabrication, which make them suitable for practical applications.

Exploration of plant-derived natural polyphenols toward COVID-19 main protease inhibitors: DFT, molecular docking approach, and molecular dynamics simulations.

Recent outbreaks of coronavirus have brought serious challenges to public health around the world, and it is essential to find effective treatments. In this study, the 3C-like proteinase (3CLpro) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been considered as an important drug target because of its role in viral replication. We initially optimized 251 compounds at the PM7 level of theory for docking with 3CLpro, and then we selected the top 12 compounds for further optimization with the B3LYP-D3/6-311G** method and obtained the top four compounds by further molecular docking. Quantum chemistry calculations were performed to predict molecular properties, such as the electrostatic potential and some CDFT descriptors. We also performed molecular dynamics simulations and free energy calculations to determine the relative stability of the selected four potential compounds. We have identified key residues controlling the 3CLpro/ligand binding from per-residue based decomposition of the binding free energy. Convincingly, the comprehensive results support the conclusion that the compounds have the potential to become a candidate for anti-coronavirus treatment.