Ultrasound-targeted microbubble destruction enhances AAV mediated gene transfection: human RPE cells in vitro and the rat retina in vivo

The present study was performed to investigate the efficacy and safety of Ultrasound-targeted microbubble destruction (UTMD) mediated rAAV2-EGFP to cultured human retinal pigment epithelium (RPE) cells _in vitro_ and the rat retina _in vivo_. _In vitro_ study, cultured human RPE cells were exposed to US under different conditions with or without microbubbles. Furthermore, the effect of UTMD to rAAV2-EGFP itself and the cells were evaluated. _In vivo_ study, gene transfer was examined by injecting rAAV2-EGFP into the subretinal space of the rats with or without microbubbles and then exposed to US. We investigated EGFP expression _in vivo_ via stereomicroscopy and performed quantitative analysis by Axiovision 3.1 software. HE staining and frozen sections were used to observe tissue damage and location of EGFP gene expression. _In vitro_ study, the transfection efficiency of rAAV2-EGFP increased 74.85% under the optimal UTMD conditions. Furthermore, there was almost no cytotoxicity to the cells and rAAV2-EGFP itself. _In vivo_ study, UTMD could be used safely to enhance and accelerate transgene expression of the retina. Fluorescence expression was mainly located in the layer of retina. UTMD is a promising method for gene delivery to the retina

Temperature-Dependent Generalized Planar Fault Energy and Twinnability of Mg Microalloyed with Er, Ho, Dy, Tb, and Gd: First-Principles Study

The generalized planar fault energies, Rice criterion ductility, and twinnability of pure Mg and Mg-RE (RE = Er, Ho, Dy, Tb, and Gd) alloys at different temperature have been investigated using density functional theory. It is shown that all the fault energies and twinnability in the same materials decrease with increasing temperature. However, the ductility has the opposite change trend. On the other hand, alloying rare earth elements will generally decrease the fault energies and increase the ductility and twinnability of Mg at different temperature. It is interesting to note that alloying larger atomic radius will enhance the ductility of Mg more easily and alloying smaller radius will make twinning tendency of Mg more easily. Finally, the electron structure further reveals the underlying mechanisms for the reduction of fault energies with the addition of rare earth elements