Cu2-xS homojunction coatings empower titanium implants with near-infrared-triggered antibacterial and antifouling properties.

For decades, implant-associated infections (IAIs) caused by pathogenic bacteria have been associated with high failure and mortality rates in implantation surgeries, posing a serious threat to global public health. Therefore, developing a functionalized biomaterial coating with anti-fouling and anti-bacterial functions is crucial for alleviating implant infections. Herein, a near-infrared-responsive anti-bacterial and anti-adhesive coating (Ti-PEG-Cu2-xS) constructed on the surface of titanium (Ti) implants is reported. This coating is composed of nano-Cu2-xS with anti-bacterial activity and super-hydrophilic polyethylene glycol (PEG). Under near-infrared irradiation, the nano-catalyst Cu2-xS on the surface of Ti-PEG-Cu2-xS induces bacterial death by catalyzing the production of singlet oxygen (1O2). The Ti-PEG-Cu2-xS coating can effectively prevent bacterial adhesion and biofilm formation. This coating combines the antibacterial mechanisms of "active attack" and "passive defense", which can kill bacteria and inhibit biofilm formation. The results of in vitro and in vivo experiments have shown that Ti-PEG-Cu2-xS exhibits excellent anti-bacterial properties under near-infrared irradiation and can effectively prevent implant-related infections caused by Escherichia coli (E. coli) ATCC 8739 and Staphylococcus aureus (S. aureus). The antibacterial efficiency of Ti-PEG-Cu2-xS coatings against E. coli was 99.96% ± 0.058% and that of S. aureus was 99.66% ± 0.26%, respectively. In addition, the Ti-PEG-Cu2-xS coating has good blood compatibility and excellent bactericidal ability. Therefore, this multifunctional coating combines a non-adhesive surface strategy and a near-infrared phototherapy sterilization method, effectively blocking the initial attachment and proliferation of bacteria on implants via photothermal/photodynamic effects and providing a promising method for preventing bacterium-induced IAIs.

Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic ß-cell survival and function.

Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), at the C-terminus of the secretory granule-enriched zinc transporter, ZnT8. Although this protein-coding variant was previously thought to be the sole driver of T2D risk at this locus, recent studies have provided evidence for lowered expression of SLC30A8 mRNA in protective allele carriers. In the present study, we examined multiple variants that influence SLC30A8 allele-specific expression. Epigenomic mapping has previously identified an islet-selective enhancer cluster at the SLC30A8 locus, hosting multiple T2D risk and cASE associations, which is spatially associated with the SLC30A8 promoter and additional neighboring genes. Here, we show that deletion of variant-bearing enhancer regions using CRISPR-Cas9 in human-derived EndoC-ßH3 cells lowers the expression of SLC30A8 and several neighboring genes and improves glucose-stimulated insulin secretion. While downregulation of SLC30A8 had no effect on beta cell survival, loss of UTP23, RAD21, or MED30 markedly reduced cell viability. Although eQTL or cASE analyses in human islets did not support the association between these additional genes and diabetes risk, the transcriptional regulator JQ1 lowered the expression of multiple genes at the SLC30A8 locus and enhanced stimulated insulin secretion.

Self-healing hydrogel based on poly (vinyl alcohol)-poly (lysine)-gum arabic accelerates diabetic wound healing under photothermal sterilization.

Diabetic wounds are a significant clinical challenge. Developing effective antibacterial dressings is crucial for preventing wound ulcers caused by bacterial infections. In this study, a self-healing antibacterial hydrogel (polyvinyl alcohol (PVA)-polylysine-gum arabic, PLG hydrogels) with near-infrared photothermal response was prepared by linking PVA and a novel polysaccharide-amino acid compound (PG) through borate bonding combined with freeze-thaw cycling. Subsequently, the hydrogel was modified by incorporating inorganic nanoparticles (modified graphene oxide (GM)). The experimental results showed that the PLGM3 hydrogels (PLG@GM hydrogels, 3.0 wt%) could effectively kill bacteria and promote diabetic wound tissue healing under 808-nm near-infrared laser irradiation. Therefore, this hydrogel system provides a new idea for developing novel dressings for treating diabetic wounds.

Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic ß-cell survival and function.

Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), at the C-terminus of the secretory granule-enriched zinc transporter, ZnT8. Although this protein-coding variant was previously thought to be the sole driver of T2D risk at this locus, recent studies have provided evidence for lowered expression of SLC30A8 mRNA in protective allele carriers. In the present study, combined allele-specific expression (cASE) analysis in human islets revealed multiple variants that influence SLC30A8 expression. Epigenomic mapping identified an islet-selective enhancer cluster at the SLC30A8 locus, hosting multiple T2D risk and cASE associations, which is spatially associated with the SLC30A8 promoter and additional neighbouring genes. Deletions of variant-bearing enhancer regions using CRISPR-Cas9 in human-derived EndoC-ßH3 cells lowered the expression of SLC30A8 and several neighbouring genes, and improved insulin secretion. Whilst down-regulation of SLC30A8 had no effect on beta cell survival, loss of UTP23, RAD21 or MED30 markedly reduced cell viability. Although eQTL or cASE analyses in human islets did not support the association between these additional genes and diabetes risk, the transcriptional regulator JQ1 lowered the expression of multiple genes at the SLC30A8 locus and enhanced stimulated insulin secretion.

Relative mRNA expression of the lactate dehydrogenase A and B subunits as determined by simultaneous amplification and single strand conformation polymorphism. Relation with subunit enzyme activity.

To explore if it is correlated in human tumor cells that the expression of LDH homologous gene and LDH isoenzymes, we used RT-PCR-SSCP technique to measure the relative expression of genes with homologous sequences. The combination of PCR using common primers designed in the highly conserved regions and single-strand conformation polymorphism analysis of the products is used for quantitative determination of the proportions of LDH-A mRNA in human cancer cell lines. The proportion is compared with that of the activities of isoenzymes. The results indicated that the enzyme activity of LDH-A was consistent with mRNA levels in the human tumor cell. The present procedure using a single pair of primers for two fragments can overcome disadvantages in quantitative analysis using multiplex PCR. Template concentrations and PCR cycles did not affect the proportions of LDH-A and LDH-B in the product.