Oxidative stress is associated with insulin resistance and secretion, and antioxidant systems are essential for preventing and managing type 2 diabetes (T2DM). This study aimed to explore the polygenic variants linked to oxidative stress and the antioxidant system among those associated with T2DM and the interaction of their polygenic risk scores (PRSs) with lifestyle factors in a large hospital-based cohort (n = 58,701). Genotyping, anthropometric, biochemical, and dietary assessments were conducted for all participants with an average body mass index of 23.9 kg/m². Genetic variants associated with T2DM were searched through genome-wide association studies in participants with T2DM (n = 5383) and without T2DM (n = 53,318). The Gene Ontology database was searched for the antioxidant systems and oxidative stress-related genes among the genetic variants associated with T2DM risk, and the PRS was generated by summing the risk alleles of selected ones. Gene expression according to the genetic variant alleles was determined on the FUMA website. Food components with low binding energy to the GSTA5 protein generated from the wildtype and mutated GSTA5_rs7739421 (missense mutation) genes were selected using in silico analysis. Glutathione metabolism-related genes, including glutathione peroxidase (GPX)1 and GPX3, glutathione disulfide reductase (GSR), peroxiredoxin-6 (PRDX6), glutamate–cysteine ligase catalytic subunit (GCLC), glutathione S-transferase alpha-5 (GSTA5), and gamma-glutamyltransferase-1 (GGT1), were predominantly selected with a relevance score of >7. The PRS related to the antioxidant system was positively associated with T2DM (ORs = 1.423, 95% CI = 1.22–1.66). The active site of the GASTA proteins having valine or leucine at 55 due to the missense mutation (rs7739421) had a low binding energy (<−10 kcal/mol) similarly or differently to some flavonoids and anthocyanins. The PRS interacted with the intake of bioactive components (specifically dietary antioxidants, vitamin C, vitamin D, and coffee) and smoking status (p < 0.05). In conclusion, individuals with a higher PRS related to the antioxidant system may have an increased risk of T2DM, and there is a potential indication that exogenous antioxidant intake may alleviate this risk, providing insights for personalized strategies in T2DM prevention.

Rhizobium leguminosarum biovar trifolii TA-1, a kind of soil bacteria, produces cyclosophoraoses (Cys). Cyclosophoraoses contain various ring sizes with degrees of polymerization ranging from 17 to 23. Atrazine is a hardly-soluble herbicide that contaminates soil and drinking water, and remains in soil for a long time. To remove this insoluble contaminant from aqueous solutions, we have enhanced the solubility of atrazine by complexation with Cys. The complex formation of Cys and atrazine was confirmed using ¹H nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), field emission scanning electron microscopy (FE-SEM), rotating frame nuclear overhauser spectroscopy (ROESY), and molecular modeling studies. The aqueous solubility of atrazine was enhanced 3.69-fold according to the added concentrations (20 mM) of Cys, compared to the 1.78-fold enhancements by β-cyclodextrin (β-CD). Cyclosophoraoses as an excellent solubility enhancer with long glucose chains that can effectively capture insoluble materials showed a potential application of microbial polysaccharides in the removal of hazardous hardly-soluble materials from aqueous solutions in the fields of biological and environmental industry.

In this study, we investigated the inhibitory potential of 60 flavonoids from six distinct subgroups on the programmed cell death ligand 1 (PD-L1) dimer through molecular docking and dynamics simulations. Using AutoDock Vina for docking, the binding poses and affinities were evaluated, revealing an average binding affinity of −8.5 kcal/mol for the flavonoids. Among them, ginkgetin exhibited the highest binding free energy of −46.73 kcal/mol, indicating a strong interaction with PD-L1, while diosmin followed closely, with −44.96 kcal/mol. Molecular dynamics simulations were used to further elucidate the dynamic interactions and stability of the flavonoid–PD-L1 complexes, with the analyses showing minimal root mean square deviation (RMSD) and favorable root mean square fluctuation (RMSF) profiles for several compounds, particularly formononetin, idaein, and neohesperidin. Additionally, contact number and hydrogen bond analyses were performed, which highlighted ginkgetin and diosmin as key flavonoids with significant binding interactions, evidenced by their stable conformations and robust molecular interactions throughout the simulations. Ultimately, a cell-based assay confirmed their ability to inhibit the proliferation of cancer cells. These results, validated through cell-based assays, indicate that the strategy of identifying natural compounds with anticancer activity using computational modeling is highly effective.