Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives.

In vivo MEO2 MA@MEO2 MA-co-OEGMA-CuS-DOX (G-CuS-DOX) nanocapsules increase the temperature of tumors from room temperature to 57 °C due to the photothermal effect under irradiation from a 915-nm laser. When the temperature exceeds 42 °C, photothermal therapy of G-CuS-DOX is switched on. Simultaneously, higher temperatures (>LCST, 42 °C) induce volume shrinkage of G-CuS-DOX in vivo, leading to the controllable release of the anticancer drug DOX. If the NIR laser is switched off, both therapy effects are interrupted immediately.

Background/Aims: Recent studies suggested the involvement of the Akt/mammalian target of rapamycin (mTOR) pathway in the pathogenesis of diabetic nephropathy. The effect of mTOR blockade by rapamycin in diabetic nephropathy was investigated, but in vivo study of rapamycin treatment in the course of early diabetes is still insufficient. This study was designed to determine the therapeutic effects of rapamycin on diabetic nephropathy at an early stage. Methods: Diabetes was induced in Sprague-Dawley rats with streptozotocin, and rapamycin (1 mg/kg) was administered by daily gavage for 4 weeks. Renal structural changes and some factors involved in the early pathogenesis of diabetic nephropathy were tested. The activation level of the Akt/mTOR pathway was also determined. Results: Rapamycin treatment reduced albuminuria, glomerular enlargement, glomerular basement membrane thickening, renal macrophage recruitment, and levels of renal mRNA expression of proliferating cell nuclear antigen, transforming growth factor-β₁, vascular endothelial growth factor, and monocyte chemoattractant protein-1 without change in blood glucose level and blood pressure in experimental diabetic rats. In addition, treatment with rapamycin also down-regulated the enhanced levels of renal p-Akt, phospho-p70S6 kinase, and phospho-ribosomal S6 protein in diabetic rats. Conclusions: Rapamycin treatment can prevent the early renal structural changes of diabetes in experimental rats, and thus halt the early steps of the development of diabetic nephropathy. mTOR blockade might be beneficial for the treatment of diabetic nephropathy.

A Meshless approach based on a Reproducing Kernel Particle Method is developed for metal forming analysis. In this approach, the displacement shape functions are constructed using the reproducing kernel approximation that satis®es consistency conditions. The variational equation of materials with loading-path dependent behavior and contact conditions is formulated with reference to the current con®guration. A Lagrangian kernel function, and its corresponding reproducing kernel shape function, are constructed using material coordinates for the Lagrangian discretization of the variational equation. The spatial derivatives of the Lagrangian reproducing kernel shape functions involved in the stress computation of path-dependent materials are performed by an inverse mapping that requires the inversion of the deformation gradient. A collocation formulation is used in the discretization of the boundary integral of the contact constraint equations formulated by a penalty method. By the use of a transformation method, the contact constraints are imposed directly on the contact nodes, and consequently the contact forces and their associated stiffness matrices are formulated at the nodal coordinate. Numerical examples are given to verify the accuracy of the proposed meshless method for metal forming analysis.