Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation

Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(−/−)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction

Error Modelling and Experimental Validation of a Planar 3-PPR Parallel Manipulator with Joint Clearances

International audienceThis paper deals with the error modelling and analysis of a 3-\underline{P}PR planar parallel manipulator with joint clearances. The kinematics and the Cartesian workspace of the manipulator are analyzed. An error model is established with considerations of both configuration errors and joint clearances. Using this model, the upper bounds and distributions of the pose errors for this manipulator are established. The results are compared with experimental measurements and show the effectiveness of the error prediction model

How do chemical patterns affect equilibrium droplet shapes?

By utilizing a proposed analytical model in combination with the phase-field method, we present a comprehensive study on the effect of chemical patterns on equilibrium droplet morphologies. Here, three influencing factors, the droplet sizes, contact angles, and the ratios of the hydrophilic area to the hydrophobic area, are contemplated. In the analytical model, chemical heterogeneities are described by different non-linear functions. By tuning these functions and the related parameters, the analytical model is capable of calculating the energy landscapes of the system. The chemically patterned surfaces display complex energy landscapes with chemical-heterogeneity-induced local minima, which correspond to the equilibrium morphologies of the droplets. Phase-field (PF) simulations are accordingly conducted and compared with the predicted equilibrium morphologies. In addition, we propose a modified Cassie–Baxter (CB) model to delineate the equilibrium droplet shapes. In contrast to the classic CB model, our extension is not only restricted to the shape with a spherical cap. Both the energy landscape method and the modified CB model are demonstrated to have a good agreement with the PF simulations

Fluoxetine Protects against Big Endothelin-1 Induced Anti-Apoptosis by Rescuing Kv1.5 Channels in Human Pulmonary Arterial Smooth Muscle Cells

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Intrinsic Lithiophilicity of Li–Garnet Electrolytes Enabling High‐Rate Lithium Cycling

Solid‐state lithium batteries are widely considered as next‐generation lithium‐ion battery technology due to the potential advantages in safety and performance. Among the various solid electrolyte materials, Li–garnet electrolytes are promising due to their high ionic conductivity and good chemical and electrochemical stabilities. However, the high electrode/electrolyte interfacial impedance is one of the major challenges. Moreover, short circuiting caused by lithium dendrite formation is reported when using Li–garnet electrolytes. Here, it is demonstrated that Li–garnet electrolytes wet well with lithium metal by removing the intrinsic impurity layer on the surface of the lithium metal. The Li/garnet interfacial impedance is determined to be 6.95 Ω cm2 at room temperature. Lithium symmetric cells based on the Li–garnet electrolytes are cycled at room temperature for 950 h and current density as high as 13.3 mA cm−2 without showing signs of short circuiting. Experimental and computational results reveal that it is the surface oxide layer on the lithium metal together with the garnet surface that majorly determines the Li/garnet interfacial property. These findings suggest that removing the superficial impurity layer on the lithium metal can enhance the wettability, which may impact the manufacturing process of future high energy density garnet‐based solid‐state lithium batteries.By removing the impurity layer on the surface of the lithium metal, Li–garnet electrolytes are demonstrated to well wet the lithium metal, rendering a Li/garnet interfacial impedance of 6.95 Ω cm2, stable galvanostatic cycling for 950 h, and a current density as high as 13.3 mA cm−2 without showing any sign of short circuiting at room temperature.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154451/1/adfm201906189-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154451/2/adfm201906189.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154451/3/adfm201906189_am.pd

Chronic Effects of a Salmonella Type III Secretion Effector Protein AvrA In Vivo

Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. AvrA is a Salmonella bacterial type III secretion effector protein. Increasing evidence demonstrates that AvrA is a multi-functional enzyme with critical roles in inhibiting inflammation, regulating apoptosis, and enhancing proliferation. However, the chronic effects of Salmonella and effector AvrA in vivo are still unknown. Moreover, alive, mutated, non-invasive Salmonella is used as a vector to specifically target cancer cells. However, studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host.We infected mice with Salmonella Typhimurium for 27 weeks and investigated the physiological effects as well as the role of AvrA in intestinal inflammation. We found altered body weight, intestinal pathology, and bacterial translocation in spleen, liver, and gallbladder in chronically Salmonella-infected mice. Moreover, AvrA suppressed intestinal inflammation and inhibited the secretion of cytokines IL-12, IFN-gamma, and TNF-alpha. AvrA expression in Salmonella enhanced its invasion ability. Liver abscess and Salmonella translocation in the gallbladder were observed and may be associated with AvrA expression in Salmonella.We created a mouse model with persistent Salmonella infection in vivo. Our study further emphasizes the importance of the Salmonella effector protein AvrA in intestinal inflammation, bacterial translocation, and chronic infection in vivo

Vitamin D receptor protects against dysbiosis and tumorigenesis via the JAK/STAT pathway in intestine

BACKGROUND & AIMS: Vitamin D exerts regulatory roles via vitamin D receptor (VDR) in mucosal immunity, host defense, and inflammation involving host factors and microbiome. Human Vdr gene variation shapes the microbiome and VDR deletion leads to dysbiosis. Low VDR expression and diminished vitamin D/VDR signaling are observed in colon cancer. Nevertheless, how intestinal epithelial VDR is involved in tumorigenesis through gut microbiota remains unknown. We hypothesized that intestinal VDR protects mice against dysbiosis via modulating the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in tumorigenesis. METHODS: To test our hypothesis, we used an azoxymethane/dextran sulfate sodium-induced cancer model in intestinal VDR conditional knockout (VDR RESULTS: VDR CONCLUSIONS: We provide insights into the mechanism of VDR dysfunction leading to dysbiosis and tumorigenesis. It indicates a new target: microbiome and VDR for the prevention of cancer