Novel Covalent Probe Selectively Targeting Glutathione Peroxidase 4 In Vivo: Potential Applications in Pancreatic Cancer Therapy.

Glutathione peroxidase 4 (GPX4) emerges as a promising target for the treatment of therapy-resistant cancer through ferroptosis. Thus, there is a broad interest in the development of GPX4 inhibitors. However, a majority of reported GPX4 inhibitors utilize chloroacetamide as a reactive electrophilic warhead, and the selectivity and pharmacokinetic properties still need to be improved.

Rapid In Situ Deposition of Iron-Chelated Polydopamine Coating on the Polyacrylamide Hydrogel Dressings for Combined Photothermal and Chemodynamic Therapy of Skin Wound Infection.

Pathogenic bacterial infections of skin wounds have caused a significant threat to clinical treatment and human life safety. Here, we develop a bactericidal hydrogel dressing consisting of a polyacrylamide (PAM) hydrogel framework with in situ surface-deposition of iron-dopped polydopamine (FePDA). The prepared hydrogel dressing (FePDA-PAM) has a compact surface, good tensile strength, and excellent elastic recovery ability.

An Ultrasmall Fe O -Decorated Polydopamine Hybrid Nanozyme Enables Continuous Conversion of Oxygen into Toxic Hydroxyl Radical via GSH-Depleted Cascade Redox Reactions for Intensive Wound Disinfection.

Nanozyme-based chemodynamic therapy (CDT) for fighting bacterial infections faces several major obstacles including low hydrogen peroxide (H O ) level, over-expressed glutathione (GSH) in infected sites, and inevitable damage to healthy tissue with abundant nonlocalized nanozymes. Herein, a smart ultrasmall Fe O -decorated polydopamine (PDA/Fe O ) hybrid nanozyme is demonstrated that continuously converts oxygen into highly toxic hydroxyl radical (•OH) via GSH-depleted cascade redox reactions for CDT-mediated bacterial elimination and intensive wound disinfection. In this system, photonic hyperthermia of PDA/Fe O nanozymes can not only directly damage bacteria, but also improve the horseradish peroxidase-like activity of Fe O decorated for CDT.

Mosaic Mutant Analysis Identifies PDGFRα/PDGFRβ as Negative Regulators of Adipogenesis.

Adipocyte progenitors (APs) express platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Elevated PDGFRα signaling inhibits adipogenesis and promotes fibrosis; however, the function of PDGFRs in APs remains unclear. We combined lineage tracing and functional analyses in a sequential dual-recombinase approach that creates mosaic Pdgfr mutant cells by Cre/lox recombination with a linked Flp/frt reporter to track individual cell fates.