Local Delivery of Glabridin by Biomolecular Microneedle to Accelerate Infected Wound Healing.

Applying antibacterial polymers and pro-regenerative small molecules are two individual strategies for accelerating wound healing. However, integrating those two unique approaches into one therapeutic platform that meets clinical requirements is still a challenge. Herein, a series of antibacterial gelatin methacrylate (GelMA)/ε-polylysine (ε-PL) composite hydrogels (termed as GP-n HGs, n = 0, 10, 20, and 30, respectively) are innovatively fabricated by ultraviolet light (UV) crosslinking. The GP-n HGs are proved to be broad-spectrum antibacterial and biocompatible. Among those GP-n HGs, the GP-20 HG is selectively processed into microneedle following a mold-casting method. Then, the glabridin is loaded into those needles to produce composite microneedle termed GP-20@Gla MN. An S. aureus-infected full-thickness defect model in rats is created to evaluate the wound-healing effect of GP-20@Gla MN. Furthermore, an RNA sequencing assay is performed to explore the possible molecular mechanisms of glabridin in promoting tissue regeneration, and many positive routes are summarized. This work is of significant novelty in fulfilling complex clinical needs by simultaneously optimizing the advanced microneedles' chemical compositions and physical structures. This work will provide a promising therapeutic platform for treating infected and chronic wounds.

Fluid Flow in Continuous Casting Mold for Ultra-Wide Slab.

Ultra-wide slabs have a good application market and prospect, but there is still a lack of research on the flow field. To explore the characteristics of its flow field, this study built a 0.5-scale physical model of mold using Perspex. The effect of casting speed on flow field and surface flow speed was investigated by using an ink tracer experiment and contact measurement. There were various flow patterns in the ultra-wide slab mold, and they continue to transform each other. The jet momentum from the nozzle ports was diffused by colliding with the wide face, which lowered its kinetic energy and affected its subsequent diffusion. Compared with the conventional mold, the upper flow intensity of the ultra-wide slab mold was weaker, which made its liquid surface inactive and caused it to produce a flux rim or slag strip. At different casting speeds, the average flow speed distribution of the ultra-wide slab was C-shaped. When it increased from 0.9 to 1.4 m/s, the corresponding maximum average flow speed increased from 0.08 to 0.2 m/s. At the same time, the proportion of the low-flow speed zone at the most active part of the surface also gradually decreased from more than 90% to about 49%.

Effects of vagotomy, splanchnic nerve lesion, and fluorocitrate on the transmission of acute hyperosmotic stress signals to the supraoptic nucleus.

The response to hyperosmotic stresses in the abdominal cavity is regulated, in part, by vasopressin (VP)-secreting neurons in the supraoptic nucleus (SON). How osmotic stress signals are transmitted to the brain is incompletely understood, and whether the transmission routes for osmotic stress signals differ between acute and chronic stresses is unknown. Here we investigated the role of the vagus, splanchnic nerves, and astrocytes in the SON in transducing acute hyperosmotic-stress signals from the abdominal cavity. We found that acute administration of hyperosmotic saline triggered the activation of neurons as well as astrocytes in the SON and the adjoining ventral glia limitans (SON-VGL). Severing the subdiaphragmatic vagal nerve (SDV) prevented the normal response of cells in the SON to HS treatment and attenuated the release of VP into the bloodstream. Lesioning the splanchnic nerves (SNL) diminished HS-induced release of VP, but to a much lesser extent than SDV. Furthermore, SNL did not significantly affect the up-regulation of Fos in SON neurons or the up-regulation of Fos and GFAP in SON and SON-VGL astrocytes that normally occurred in response to HS and did not affect HS-induced expansion of the SON-VGL. Inhibiting astrocytes with fluorocitrate (FCA) prevented the response of the SON to HS and attenuated the release of VP, similarly to SDV surgery. These results suggest that the vagus is the principle route for the transmission of hyperosmotic signals to the brain and that astrocytes in the SON region are necessary for the activation of SON neurons and the release of VP into the bloodstream.