SKAP2

Surface-active peptides (SAPs) typically mimic conventional surfactants by featuring long non-polar (hydrophobic) peptide tails and short polar (hydrophilic) heads consisting of a single amino acid or short peptide. However, reverse-structure SAPs-with a long hydrophilic tail and short hydrophobic head-remain largely unexplored. If developed, such SAPs could form micelles with a larger hydrophilic area and a smaller hydrophobic core, leading to novel self-assembled structures. We hypothesize that combining the self-assembly potential of an aromatic moiety as a short hydrophobic head with the linear hydrophilic properties of collagen-like peptides containing Glycine-Proline-Hydroxyproline (GPO) repeats can lead to the development of these unique reverse SAPs. These SAPs are expected to form unique self-assembled structures with a larger hydrophilic area and a smaller hydrophobic core, contributing to advancements in colloidal and interface science. To validate this hypothesis, π-system-functionalized collagen-like peptides were designed using (GPO)_n (n = 1-5) as extended hydrophilic tails and a fluorenyl aromatic π-system as the hydrophobic head. Biophysical studies evaluated their self-assembly, critical micellar concentration, and surface activity, focusing on stabilization mechanisms driven by aromatic π-π interactions and hydrogen bonding. The SAPs exhibited surface activity and formed micelles at sub-millimolar concentrations. Longer hydrophilic tails resulted in lower CMC values, indicating enhanced self-assembly. The micelles were stabilized by π-π stacking and hydrogen bonding, creating unique self-assembled structures with a larger hydrophilic region and a smaller hydrophobic core. These findings provide new insights into colloids and interface science and open avenues for applying reverse-structure SAPs in drug delivery.

Vancomycin is frequently monitored, but target levels for continuous infusion of vancomycin (CIV) are based on expert opinion. Rarely have vancomycin concentrations been correlated with therapeutic efficacy or safety of CIV.

Associations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined.

A retrospective, single-centre cohort study was conducted of consecutive critically ill surgical patients receiving CIV between 2010 and 2022. After detecting associations between vancomycin levels, renal function and health status, four subgroups were defined based on estimated glomerular filtration rate (36). Failure and toxicity of vancomycin serum concentrations were assessed using primary (mortality, acute kidney injury (AKI)) and secondary (clinical and microbiological failure) endpoints. Predictors of outcome parameters were identified using logistic and Cox regression. Concentrations were compared by bivariate comparisons, post-hoc tests following analysis of variance for the regression models and desirability of outcome ranking. Concentration cut-offs were determined by receiver-operating characteristic and classification and regression tree analyses.

922 patients were included. Higher vancomycin concentrations (first 72 h average, specifically >25 mg/L) were associated with higher mortality, AKI and clinical failure, but less microbiological failure. For SAPS>36, concentrations <20 mg/L (i.e. 15-20 mg/L or <17 mg/L) correlated with the best treatment outcome, for SAPS≤36 concentrations >19 mg/L (i.e. 20-25 mg/L or 19-28 mg/L).

Retrospective analyses of vancomycin serum concentrations during CIV suggest that ICU patients' disease severity should be considered when selecting a target concentration. The target concentration might be sought inversely related to SAPS, which should be confirmed in future prospective controlled trials.

The alarming prevalence of environmental microplastics has raised global concerns about fertility. However, the detriment of polytetrafluoroethylene (PTFE, Teflon), a widely used microplastic in non‐stick cookware, to sperm quality remains unclear. Here, a high detection rate (46.62%) and bioaccumulation of PTFE in the male urogenital system are reported and the mechanisms of PTFE exposure on male fertility are investigated in both humans and mice and potential therapeutic strategies are explored. These findings reveal that PTFE exposure delays the development of spermatogonia and spermatocytes, disrupts chromosomal synapsis and the DNA damage response, and promotes the apoptosis of spermatocytes. Interestingly, PTFE exposure specifically targets SKAP2 in the haploid spermatid, leading to disruption of the sperm cytoskeleton, abnormal sperm morphology, and decreased sperm motility. Strikingly, therapy targeting SKAP2 remodels sperm cytoskeleton and morphology and restores sperm motility and male fertility in humans and mice. Collectively, these works illustrate the mechanisms of PTFE exposure impairing spermatogenesis and highlight SKAP2 targeting as a promising therapeutic strategy for treating asthenoteratozoospermia in humans.