Polyzwitterionic micelles with antimicrobial-conjugation for eradication of drug-resistant bacterial biofilms.

The presence of bacterial biofilms has presented a significant challenge to human health. This study presents the development of biofilm microenvironment-responsive polymeric micelles as a novel approach to address the challenges posed by bacterial biofilms. These micelles are composed of two key components: a zwitterionic component, inspired by protein isoelectric points, containing balanced quantities of primary amines and carboxylic groups that undergo a positive charge transformation in acidic microenvironments, and a hydrophobic triclosan conjugate capable of releasing triclosan in the presence of bacterial lipases. Through the synergistic combination of pH-responsiveness and lipase-responsiveness, we have significantly improved drug penetration into biofilms and enhanced its efficacy in killing bacteria. With their remarkable drug-loading capacity and the ability to specifically target and eliminate bacteria within biofilms, these zwitterionic polymeric micelles hold great promise as an effective alternative for treating biofilm-associated infections. Their unique properties enable efficient drug delivery and heightened effectiveness against biofilm-related infections.

Genomic DNA methylation in HLA-Cw*0602 carriers and non-carriers of psoriasis.

BACKGROUND: HLA-Cw*0602 has long been established as one of the most important genetic biomarkers in psoriasis. However, the epigenetic and gene expression differences between HLA-Cw*0602 carriers and non-carriers has not yet been investigated. OBJECTIVE: We aim to explore the whole-genome methylation and gene expression differences between HLA-Cw*0602 carriers and non-carriers. METHODS: HLA imputation was performed to get landscape of variants in this region. Genome-wide DNA methylation was compared between positive and negative HLA-Cw*0602 groups. Eleven methylation loci were selected for further validation in additional 43 cases. For differentially methylated genes, GO and KEGG were used to annotate gene functions. RESULTS: We imputed 29,948 variants based on the constructed HLA reference panels, and obtained 42 HLA-Cw*0602 carriers and 72 non-carriers. Significant methylation differences were detected at 4321 sites (811 hypo- and 3510 hypermethylated). The cg02607779 (KLF7, P = 0.001), cg06936779 (PIP5K1A, P = 0.002), cg03860400 (BTBD10, P = 0.017) and cg26112390 (GOLGA2P5, P = 0.019) were identified and validated to be the significant CpGs contributed to different HLA-C*0602 groups. Among the hypo- and hypermethylated sites, the top CpGs were in gene body and CpG island. CONCLUSION: We performed the first whole-genome study on methylation differences between psoriatic individuals with or without HLA-Cw*0602, and found the key methylation sites which may contribute to the carrying status of HLA-Cw*0602. Methylation loci located in gene body and CpG island are more likely to affect the methylation levels in HLA-Cw*0602 carriers. This integrated analysis shed light on novel insights into the pathogenic mechanisms of genomic methylation in different HLA genotypes of psoriasis.