Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca^(2+) entry in glomerular mesangial cells

Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca^(2+) entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high-glucose-increased Smad1 protein content. Treatment of human MCs with ANG II at 1 µM for 15 min, high glucose for 3 days, or TGF-β1 at 5 ng/ml for 30 min increased the level of phosphorylated Smad1. However, the phosphorylation of Smad1 by those stimuli was significantly attenuated by activation of SOCE. Knocking down Smad1 reduced, but expressing Smad1 increased, the amount of Col IV protein. Furthermore, activation of SOCE significantly attenuated high-glucose-induced Col IV protein production, and blockade of SOCE substantially increased the abundance of Col IV. To further verify those in vitro findings, we downregulated SOCE specifically in MCs in mice using small-interfering RNA (siRNA) against Orai1 (the channel protein mediating SOCE) delivered by the targeted nanoparticle delivery system. Immunohistochemical examinations showed that expression of both Smad1 and Col IV proteins was significantly greater in the glomeruli with positively transfected Orai1 siRNA compared with the glomeruli from the mice without Orai1 siRNA treatment. Taken together, our results indicate that SOCE negatively regulates the Smad1 signaling pathway and inhibits Col IV protein production in MCs

Single Image Super-Resolution Using Multi-Scale Deep Encoder-Decoder with Phase Congruency Edge Map Guidance

This paper presents an end-to-end multi-scale deep encoder (convolution) and decoder (deconvolution) network for single image super-resolution (SISR) guided by phase congruency (PC) edge map. Our system starts by a single scale symmetrical encoder-decoder structure for SISR, which is extended to a multi-scale model by integrating wavelet multi-resolution analysis into our network. The new multi-scale deep learning system allows the low resolution (LR) input and its PC edge map to be combined so as to precisely predict the multi-scale super-resolved edge details with the guidance of the high-resolution (HR) PC edge map. In this way, the proposed deep model takes both the reconstruction of image pixels’ intensities and the recovery of multi-scale edge details into consideration under the same framework. We evaluate the proposed model on benchmark datasets of different data scenarios, such as Set14 and BSD100 - natural images, Middlebury and New Tsukuba - depth images. The evaluations based on both PSNR and visual perception reveal that the proposed model is superior to the state-of-the-art methods

Low-Carbon and Nanosheathed ZnCo2O4 Spheroids with Porous Architecture for Boosted Lithium Storage Properties

Multielectronic reaction electrode materials for high energy density lithium-ion batteries (LIBs) are severely hindered by their inherent sluggish kinetics and large volume variations, leading to rapid capacity fade. Here, a simple method is developed to construct low-carbon and nanosheathed ZnCo2O4 porous spheroids (ZCO@C-5). In this micro/nanostructure, an ultrathin amorphous carbon layer (~2 nm in thickness) is distributed all over the primary nanosized ZCO particles (~20 nm in diameter), which finally self-assembles into porous core (ZCO)-shell(carbon) micron spheroids. The nanoencapsulation and macro/mesoporous architecture can not only provide facile electrolyte penetration and rapid ion/electron transfer but also better alleviate volumetric expansion effect to avoid pulverization of ZCO@C-5 spheroids during repeat charge/discharge processes. As expected, the three-dimensional porous ZCO@C-5 composites exhibit high reversible capacity of 1240 mAh g−1 cycle at 500 mA g−1, as well as excellent long-term cycling stability and rate capability. The low-carbon and nanoencapsulation strategy in this study is simple and effective, exhibiting great potential for high-performance LIBs

A Novel Gel Polymer Electrolyte by Thiol-Ene Click Reaction Derived from CO2-Based Polycarbonate for Lithium-Ion Batteries

Here, we describe the synthesis of a CO2-based polycarbonate with pendent alkene groups and its functionalization by grafting methoxypolyethylene glycol in view of its application possibility in gel polymer electrolyte lithium-ion batteries. The gel polymer electrolyte is prepared by an in-situ thiol-ene click reaction between polycarbonate with pendent alkene groups and thiolated methoxypolyethylene glycol in liquid lithium hexafluorophosphate electrolyte and exhibits conductivity as remarkably high as 2.0×10−2 S cm−1 at ambient temperature. To the best of our knowledge, this gel polymer electrolyte possesses the highest conductivity in all relevant literatures. A free-standing composite gel polymer electrolyte membrane is obtained by incorporating the gel polymer electrolyte with electrospun polyvinylidene fluoride as a skeleton. The as-prepared composite membrane is used to assemble a prototype lithium iron phosphate cell and evaluated accordingly. The battery delivers a good reversible charge-discharge capacity close to 140 mAh g-1 at 1 C rate and 25°C with only 0.022% per cycle decay after 200 cycles. This work provides an interesting molecular design for polycarbonate application in gel electrolyte lithium-ion batteries

Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation

Background/Aims: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. Methods: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. Results: The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR) expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of “stemness” genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD) significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS) levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK) signaling pathway. Conclusions: LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored