Five glycosylation-related gene signatures predict the prognostic risks of lung adenocarcinoma.

This study aimed to identify glycosylation-related genes associated with lung adenocarcinoma (LUAD) prognosis through comprehensive bioinformatic analysis. Glycosylation-related genes were identified from the Human Gene Nomenclature Committee, and LUAD prognostic genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)-GSE68465 datasets. Glycosylation risk score (GLRS) was calculated to predict LUAD prognostic risk. Samples were grouped into GLRS-high and GLRS-low and compared. The Tumor Immune Dysfunction and Exclusion (TIDE) score was computed to assess the antitumor immune escape possibility after immunotherapy. From 213 glycosylation-related genes, five gene signatures served as prognostic LUAD predictors using univariate and stepwise Cox regression analyses. GLRS-based models were constructed using TCGA and GSE68465 samples; their sensitivity and specificity in predicting LUAD prognosis were confirmed. GLRS was an independent LUAD prognostic factor and contributed to the nomogram to predict patient survival. High GLRS was associated with advanced tumor stage and higher mutation frequencies, estimate scores, and TIDE scores. GLRS-high and GLRS-low patients differed in immune cell infiltration and epithelial-mesenchymal transition (EMT)-related gene expression. Thus, we propose five glycosylation-related gene signatures to predict overall survival and prognostic risks of LUAD. Their regulatory roles may be related to immune invasion, immunotherapy response, mutation, and EMT.

Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.

The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51-94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) and 5-(9H-carbazol-2-yl) benzene-1,2,3-triol (6m) showed the most potent inhibitory activities against methicillin-resistant Staphylococcus aureus and multidrug-resistant Enterococcus faecalis with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 µg/mL, respectively. Compounds 3',5'-dimethyl-[1,1'-biphenyl]-3,4,4',5-tetraol (6e), 4'-fluoro-[1,1'-biphenyl]-3,4,5-triol (6g), and 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant Acinetobacter baumannii. Study of the structure-activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, N-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.