ABSTRACT
Chemoresistance is a key obstacle in the long-term survival of patients with locally and advanced lung adenocarcinoma (LUAD). This study used bioinformatic analysis to reveal the chemoresistance of gene-neutrophil extracellular traps (NETs) associated with LUAD. RNA sequencing data and LUAD expression patterns were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. The GeneCards database was used to identify NETosis-related genes (NRGs). To identify hub genes with significant and consistent expression, differential analysis was performed using the TCGA-LUAD and GEO datasets. LUAD subtypes were determined based on these hub genes, followed by prognostic analysis. Immunological scoring and infiltration analysis were conducted using NETosis scores (N-scores) derived from the TCGA-LUAD dataset. A clinical prognostic model was established and analyzed, and its clinical applications explored. Twenty-two hub genes were identified, and consensus clustering was used to identify two subgroups based on their expression levels. The Kaplan-Meier (KM) curves demonstrated statistically significant differences in prognosis between the two LUAD subtypes. Based on the median score, patients were further divided into high and low N-score groups, and KM curves showed that the N-scores were more precise at predicting the prognosis of patients with LUAD for overall survival (OS). Immunological infiltration analysis revealed significant differences in the abundances of 10 immune cell infiltrates between the high and low N-score groups. Risk scores indicated significant differences in prognosis between the two extreme score groups. The risk scores for the prognostic model also indicated significant differences between the two groups. The results provide new insights into NETosis-related differentially expressed genes (NRDEGs) associated with chemotherapy resistance in patients with LUAD. The established prognostic model is promising and could help with clinical applications to evaluate patient survival and therapeutic efficiency.
ABSTRACT
Mechanism research of nanozymes has always been of great interest since their emergence as outstanding mimics of friable natural enzymes. An important but rarely mentioned issue in mechanism research of nanozymology is the inhibitory effect of nanozymes. And conventional nanozymes with various active sites hinder the mechanism research, while single-atom Fe-N-C nanozymes with similar active sites to natural enzymes exhibit structural advantages. Herein, we synthesized Fe single-atom nanozymes (Fe-SANs) with ultrahigh oxidase-like activity and found that a common analgesic-antipyretic drug 4-acetamidophenol (AMP) had inhibitory effects for the oxidase-like activity of Fe-SANs. We investigated the inhibitory effects in detail and demonstrated that the inhibition type was reversible mixed-inhibition with inhibition constants (K i and ) of 0.431 mM and 0.279 mM, respectively. Furthermore, we put forward a colorimetric method for AMP detection based on nanozyme inhibition. The research on the inhibitory effects of small molecules on nanozymes expands the scope of analysis based on nanozymes and the inhibition mechanism study may offer some insight into investigating the interaction between nanozymes and inhibitors.
