We report that K5.Smad7 mice, which express Smad7 transgene by a keratin-5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to NF-κB activation known to contribute to oral mucositis, we found activated TGF-β signaling in oral mucositis. Smad7 dampened both pathways to attenuate inflammation, growth inhibition and apoptosis. Additionally, Smad7 promoted oral epithelial migration to close the wound. Further analyses revealed that TGF-β signaling Smads and their co-repressor CtBP1 transcriptionally repressed Rac1, and Smad7 abrogated this repression. Knocking down Rac1 in mouse keratinocytes abrogated Smad7-induced migration. Topically applying Smad7 protein with a cell permeable Tat-tag (Tat-Smad7) to oral mucosa showed preventive and therapeutic effects on radiation-induced oral mucositis in mice. Thus, we have identified novel molecular mechanisms involved in oral mucositis pathogenesis and our data suggest an alternative therapeutic strategy to block multiple pathological processes of oral mucositis.

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To overcome the inherent high hysteresis loss of ferroelectric polymer-based nanocomposites, non-ferroelectric linear dielectric poly(methyl methacrylate) (PMMA) is adopted as the polymer matrix for high discharge efficiency. At the same time, slender ferroelectric BaTiO 3 nanowires (BT NWs) with a high dielectric constant are selected as the nanofiller for high energy density. To avoid the agglomeration of BT NWs and enhance the strength of interfaces, dopamine is used as organic coatings to tailor the interface. The BT@dopa NWs/PMMA nanocomposites exhibit excellent interface compatibility between the BT NWs and PMMA matrix and a very good microstructure uniformity. Based on this, hierarchically structured BT@SiO 2 @dopa NWs are designed and prepared to overcome the uneven electric field distribution at the interface, resulting from the dielectric constant mismatch. The discharged energy density (U e ) can be largely enhanced from 3.76 J/cm 3 for pure PMMA films to 11.78 J/cm 3 for PMMA-based nanocomposites by incorporating 5.0 wt % BT@SiO 2 @dopa NWs. In addition, a high discharging efficiency (η) of 91% is obtained simultaneously in the nanocomposites. Both experimental and theoretical simulations demonstrate that the double core−shell structure nanowire fillers can effectively alleviate the local field distortion, inhibit leakage current, and suppress remnant electric displacement, leading to the high U e and η. These findings are significant in facilitating the development of high-performance film dielectric capacitor materials using PMMA-based nanocomposites toward high energy storage density.

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The flow behavior of the fluid has a significant effect on the particle distribution in the solid-liquid mixing vessel. The stir casting process is generally conducted in a closed crucible, in which the flow pattern is invisible. Therefore, numerical simulation is a forceful tool to guide the experimental research. In the present study, the fluid flow in the stirred crucible during stir casting has been simulated using finite element method. The effects of some important stirring process parameters, such as the blade angle, rotating speed, the diameter of the impeller, and the stirrer geometry, on the flowing characteristics of the molten matrix have been investigated in order to achieve the effective flow pattern to uniformly disperse the ceramic particles in the molten matrix. The simulation results show that the process parameters have significant effects on the flow behavior of the fluid in the stirred crucible. The various combinations of these parameters are beneficial to generate a suitable condition for the composite casting. Further experimental investigation reveals that the present work can provide a guide for the industrial preparation of aluminum matrix composite with a uniform particle reinforcement distribution by stir casting process.