To develop biocompatible composite microspheres for novel hemostatic use, we designed and prepared a novel biomaterial, composite microspheres consisting of carboxymethyl chitosan, sodium alginate, and collagen (CSCM). The ultra-structure of CSCM was investigated by scanning electron microscopy assay. In hemostatic function experiment, it was found that CSCM could facilitate platelet adherence, platelet aggregation, and platelet activation in vitro. Besides, the maximum swelling of CSCM submerged in PBS for 50 min was over 300% of that exhibited by commercial hemostatic compound microporous polysaccharide haemostatic powder (CMPHP). In addition, CSCM exhibited good biodegradability and non-cytotoxicity. These results demonstrated that CSCM may be useful in platelet plug formation, and this study would provide important information for further research on hemostasis experiment in vivo.

Due to the rise in bacterial resistance, the antibacterial extractions from Chinese herbs have been used more frequently for wound care. In this work, baicalin, an extraction from the Chinese herb Scutellaria baicalensis, was utilized as the antibacterial component in the poly(ε-caprolactone)/MXene (PCL/Ti₃C₂T_X) hybrid nanofibrous membranes for wound dressing. The results revealed that the presence of Ti₃C₂T_X aided in the diameter reduction of the electrospun nanofibers. The PCL hybrid membrane containing 3 wt% Ti₃C₂T_X nanoflakes and 5 wt% baicalin exhibited the smallest mean diameter of 210 nm. Meanwhile, the antibacterial tests demonstrated that the PCL ternary hybrid nanofibers containing Ti₃C₂T_X and baicalin exhibited adequate antibacterial activity against the Gram-positive bacterial S. aureus due to the good synergistic effects of Ti₃C₂T_X naoflakes and baicalin. The addition of Ti₃C₂T_X nanoflakes and baicalin could significantly improve the hydrophilicity of the membranes, resulting in the release of baicalin from the nanofibers. In addition, the cytotoxicity of the nanofibers on rat skeletal myoblast L6 cells confirmed their good compatibility with these PCL-based nanofibrous membrances. This work offers a feasible way to prepare antibacterial nanofibrous membranes using Chinese herb extraction for wound dressing applications.

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia. However, development of uncoupler-based therapy remains challenging due to its potentially lethal adverse effects. Here, we identify pyruvate dehydrogenase (PDH) as a key modifier of the toxicity profile of 2, 4-dinitrophenol (DNP), a prototypical mitochondrial uncoupler. PDH activation by dichloroacetic acid (DCA) protects mice from DNP-induced hyperlactacidemia, hyperthermia, and death while preserving the ability of DNP to promote fuel oxidation and improve insulin sensitivity in mice. Mechanistically, PDH activation switches on mitochondrial glucose oxidation to accommodate increased glycolytic flux, leading to reduced lactate secretion during uncoupler treatments. We devised a chemical screening strategy and discovered compound 6j as a dual-action compound that simultaneously activates PDH and uncouples mitochondrial respiration. Compound 6j exhibits an excellent efficacy and safety profile in restoring glucose homeostasis in diabetic mice. This work establishes a new principle to safely harness the power of chemical uncouplers for the treatment of metabolic disease.