Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via PLCγ, PKC, and PI3K/Akt pathways during colitis

Background Spinal central sensitization is an important process in the generation and maintenance of visceral hypersensitivity. The release of brain-derived neurotrophic factor (BDNF) from the primary afferent neurons to the spinal cord contributes to spinal neuronal plasticity and increases neuronal activity and synaptic efficacy. The N-Methyl-D-aspartic acid (NMDA) receptor possesses ion channel properties, and its activity is modulated by phosphorylation of its subunits including the NMDA receptor 1 (NR1). Methods Colonic inflammation was induced by a single dose of intracolonic instillation of tri-nitrobenzene sulfonic acid (TNBS). NR1 phosphorylation by BDNF in vivo and in culture was examined by western blot and immunohistochemistry. Signal transduction was studied by direct examination and use of specific inhibitors. Results During colitis, the level of NR1 phospho-Ser896 was increased in the dorsal horn region of the L1 and S1 spinal cord; this increase was attenuated by injection of BDNF neutralizing antibody to colitic animals (36 μg/kg, intravenous (i.v.)) and was also reduced in BDNF+/− rat treated with TNBS. Signal transduction examination showed that the extracellular signal-regulated kinase (ERK) activation was not involved in BDNF-induced NR1 phosphorylation. In contrast, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediated BDNF-induced NR1 phosphorylation in vivo and in culture; this is an additional pathway to the phospholipase C-gamma (PLCγ) and the protein kinase C (PKC) that was widely considered to phosphorylate NR1 at Ser896. In spinal cord culture, the inhibitors to PLC (U73122), PKC (bisindolylmaleimide I), and PI3K (LY294002), but not MEK (PD98059) blocked BDNF-induced NR1 phosphorylation. In animals with colitis, treatment with LY294002 (50 μg/kg, i.v.) blocked the Akt activity as well as NR1 phosphorylation at Ser896 in the spinal cord. Conclusion BDNF participates in colitis-induced spinal central sensitization by up-regulating NR1 phosphorylation at Ser896. The PI3K/Akt pathway, in addition to PLCγ and PKC, mediates BDNF action in the spinal cord during colitis

BMP4 inhibits myogenic differentiation of bone marrow–derived mesenchymal stromal cells in mdx mice

AbstractBackground aimsBone marrow–derived mesenchymal stromal cells (BMSCs) are a promising therapeutic option for treating Duchenne muscular dystrophy (DMD). Myogenic differentiation occurs in the skeletal muscle of the mdx mouse (a mouse model of DMD) after BMSC transplantation. The transcription factor bone morphogenic protein 4 (BMP4) plays a crucial role in growth regulation, differentiation and survival of many cell types, including BMSCs. We treated BMSCs with BMP4 or the BMP antagonist noggin to examine the effects of BMP signaling on the myogenic potential of BMSCs in mdx mice.MethodsWe added BMP4 or noggin to cultured BMSCs under myogenic differentiation conditions. We then injected BMP4- or noggin-treated BMSCs into the muscles of mdx mice to determine their myogenic potential.ResultsWe found that the expression levels of desmin and myosin heavy chain decreased after treating BMSCs with BMP4, whereas the expression levels of phosphorylated Smad, a downstream target of BMP4, were higher in these BMSCs than in the controls. Mdx mouse muscles injected with BMSCs pretreated with BMP4 showed decreased dystrophin expression and increased phosphorylated Smad levels compared with muscles injected with non-treated BMSCs. The opposite effects were seen after pretreatment with noggin, as expected.ConclusionsOur results identified BMP/Smad signaling as an essential negative regulator of promyogenic BMSC activity; inhibition of this pathway improved the efficiency of BMSC myogenic differentiation, which suggests that this pathway might serve as a target to regulate BMSC function for better myogenic differentiation during treatment of DMD and degenerative skeletal muscle diseases

Experimental Study on Flow Boiling Characteristics in Continuous and Segmented Microchannels with Vapor Venting Membrane

Flow boiling in microchannels is one of the promising techniques for heat dissipation occurred in micro devices. However, the rapid bubble growth must be suppressed, which leads to serious boiling instabilities, high pressure drop, and low heat transfer coefficient. The addition of porous hydrophobic membrane has proven an effective method to remove the vapor in-site in the literature. However, the effects of heat sink’s topological structures on the vapor venting are still a research gap. The present study experimentally investigates the influence of Polytetrafluoroethylene (PTFE) membrane on fluid flow pattern, pressure drop, vapor venting performance, and heat transfer characteristics of flow boiling in the continuous and segmented heat sinks. Results show that the vapor venting membrane can reduce the pressure drop and increase the heat transfer coefficient effectively by decreasing the exit vapor quality, especially in combination with the segmented structures. The interconnection area as a space for bubble growth and coalescence is beneficial for vapor venting due to increased vapor pressure and quantity. Following the enhanced vapor discharge, the fluctuation of pressure drop is further weakened, which is conducive for the safe operation of heat sink

Anisotropic flows without global terms and dual Orlicz Christoffel-Minkowski type problem

In this paper, we study the long-time existence and asymptotic behavior for a class of anisotropic non-homogeneous flows without global terms. By the stationary solutions of anisotropic flows if they exist, we obtain a class of results for the dual Orlicz Christoffel-Minkowski type problem with $c=1$, which is equivalent to solve the PDE $G(x,u_K,\bar\nabla u_K)F(D^2u_K+u_KI)=c$ on $\mathbb S^n$ for a convex body $K$. Here $D$ and $\bar\nabla$ are the covariant derivative with respect to the standard metric on $\mathbb S^n$ and Euclidean space respectively, $I$ is the unit matrix of order $n$, and $\bar\nabla u_K(x):=Du_K(x)+u_K(x)x$ is the point on $\partial K$ whose outer unit normal vector is $x\in\mathbb S^n$. In the dual Orlicz-Minkowski problem and Orlicz Christoffel-Minkowski problem, the constant $c$ can't be set to $1$ in general. The highlight of our arguments is that we use anisotropic flows without global terms to set $c=1$. This result covers many previous known solutions to $L^p$ dual Minkowski problem, $L^p$-Christoffel-Minkowski problem, etc.. In particular, we give a convergence result of anisotropic flows with general curvature function and arbitrarily initial strictly convex hypersurface if $G(x,u_K,\bar\nabla u_K)=\psi(x)u^{\alpha-1}\vert\bar\nabla u\vert^\delta=\psi(x)u^{\alpha-1}\rho^\delta$, where $\rho$ is the radial function. To the best of our knowledge, there is no other convergence result about anisotropic flows with general curvature function and arbitrarily initial strictly convex hypersurface. Finally we give two uniqueness results in some particular cases.Comment: arXiv admin note: text overlap with arXiv:2203.0216

Steady-state modeling of axial heterogeneity in CFB risers based on one-dimensional EMMS model

Axial heterogeneity in circulating fluidized bed (CFB) risers is very important to the design of fluidized bed reactors, which is, however, still unable to be described in theory. Based on a successful description of local hydrodynamics in gas solid flow, the Energy-Minimization Multi-Scale (EMMS) theory further relates axial hydrodynamics with local and global stability conditions in the system, providing a theoretical way to account for the axial heterogeneity in CFB risers. This research reveals that the interaction between particle clusters and the dilute phase as well as the surrounding dense phase has a significant effect on their dynamical evolution. Similar to cluster diameter in the EMMS theory, number density of particle clusters serving as a comprehensive indicator to the heterogeneity in gas solid flow is constrained by both local and global stability conditions in the system. With the above cognition, a one-dimensional EMMS model is developed to perform steady-state modeling of the axial heterogeneity in CFB risers. The model successfully reproduces a complete transition zone and the parametric effects on it at the choking condition. The S-shaped axial voidage profile calculated by the one-dimensional EMMS model is in good agreement with the experimental results in gas solid fast fluidization. This research is not only the first step toward implementing the three-scale computation in virtual process engineering (VPE), but also of referential significance to industrial chemical process development. (C) 2013 Elsevier Ltd. All rights reserved

Preparation of Activated Carbon from Pyrolyzed Rice Husk by Leaching out Ash Content after CO2 Activation

To prepare activated carbons with a high porosity and low ash content from pyrolyzed rice husk, the method of KOH or K2CO3 solution leaching after CO2 activation was investigated. The effects of KOH or K2CO3 concentration and leaching time on the yield, ash content, and textural properties of the activated carbon were studied, and the activated carbon prepared under the best conditions was characterized. The results showed that the best leaching time was 1 h for KOH and K2CO3, and the best concentrations were 1.0 and 4.0 M, respectively. The leaching process was greatly beneficial to the development of the pore structure. The specific surface area of the activated carbon prepared under the most favorable conditions was approximately 1100 m2/g, and the iodine values were greater than 1100 mg/g. As a result of the leaching process, the ash content of the sample was notably decreased from 63% to approximately 5%, and the porosity development was attributed to the reaction of the leaching reagents with silica