Multi-Component Lithiophilic Alloy Film Modified Cu Current Collector for Long-Life Lithium Metal Batteries by a Novel FCVA Co-Deposition System.

Surface modification of Cu current collectors (CCs) is proven to be an effective method for protecting lithium metal anodes. However, few studies have focused on the quality and efficiency of modification layers. Herein, a novel home-made filtered cathode vacuum arc (FCVA) co-deposition system with high modification efficiency, good repeatability and environmental friendliness is proposed to realize the wide range regulation of film composition, structure and performance. Through this system, ZnMgTiAl quaternary alloy films, which have good affinity with Li are successfully constructed on Cu CCs, and the fully enhanced electrochemical performances are achieved. Symmetrical cells constructed with modified CCs maintained a fairly low voltage hysteresis of only 13 mV after 2100 h at a current density of 1 mA cm-2. In addition, the capacity retention rate is as high as 75.0% after 100 cycles in the full cells. The influence of alloy films on the dynamic evolution process of constructing stable artificial solid electrolyte interphase (SEI) layer is revealed by in situ infrared (IR) spectroscopy. This work provides a promising route for designing various feasible modification films for LMBs, and it displays better industrial application prospects than the traditional chemical methods owing to the remarkable controllability and scale-up capacity.

Altered mitochondrial expression genes in patients receiving right ventricular apical pacing.

Left ventricular mechanical dyssynchrony from right ventricular apical (RVA) pacing may lead to heart failure. Mitochondrial dysfunction has been observed in the failing heart; however, whether RVA pacing may alter the underlying mitochondrial dynamics at an early stage in patients with preserved ejection fraction is not well understood. RNA was isolated from peripheral whole blood samples of 13 patients. The differentially expressed mRNA profiles from 58 samples (13 experimental subjects; 35 control subjects) were performed using Affymetrix array. Finally, a five-gene signature was identified. DAVID was performed to explore the biological functions of target genes with altered gene expression between two groups. The gene signature (OPA1, CTSA, NDUFA1, STK10 and PRDX1) was able to identify patients post-implant with an area under receiver operating characteristic curve of 0.90 in this study. Our test showed that the gene signature had a sensitivity of 91% with a specificity of 86% in discrimination between post-implant group and healthy controls. In the cellular component category, four genes of the five-gene signature except STK10 were related to mitochondrion. The five-gene signature was associated with oxidative phosphorylation, mitochondrial ATP synthesis and apoptosis in biological process analysis. Pathway analysis indicated that a significant enrichment of candidate genes involved in the calcium signaling and glycosphingolipid biosynthesis pathways. The expression changes observed in this study reflect a profound effect of ventricular mechanical dyssynchrony caused by RVA pacing on the transcriptome at an early stage. RVA pacing alters cellular energy metabolism may have association with mitochondrial dynamics.

Increased mortality and aggravation of heart failure in liver X receptor-α knockout mice after myocardial infarction.

Liver X receptors, LXRα (NR1H3) and LXRß (NR1H2), are best known as nuclear oxysterol receptors and physiological master regulators of lipid and cholesterol metabolism. LXRα play a protective role in acute myocardial ischemia/reperfusion (MI/R) injury, but its role in myocardial infarction (MI) is unknown. The present study was undertaken to determine the effect of LXRα knockout on survival and development of chronic heart failure after MI. Wild-type (WT) and LXRα(-/-) mice were subjected to MI followed by serial echocardiographic and histological assessments. Greater myocyte apoptosis and inflammation within the infarcted zones were found in LXRα(-/-) group at 3 days after MI. At 4 weeks post-MI, LXRα(-/-) MI murine hearts demonstrated significantly increased infarct size, reduced ejection fraction (LXRα(-/-) 29.4 % versus WT 34.4 %), aggravated left ventricular (LV) chamber dilation, enhanced fibrosis and reduced angiogenesis. In addition, LXRα(-/-) mice had increased mortality compared with WT mice. LXRα deficiency increases mortality, aggravates pathological injury and LV remodeling induced by MI. Drugs specifically targeting LXRα may be promising in the treatment of MI.

Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction.

In the present study, we investigated whether mesenchymal stem cells (MSCs) overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs (ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri-infarct myocardium 7 days after ligation of the left anterior descending coronary artery. ILK expression was confirmed by immunofluorescence, real-time PCR, Western blot analysis, and flow cytometry. In vitro assays indicated increased proliferation and reduced apoptosis of MSCs due to overexpression of ILK. Echocardiographic, single-photon emission computed tomography and positron emission tomography analyses demonstrated preserved cardiac function and myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation, and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling and cardiac function in pigs after MI. It is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of post-infarct remodeling and subsequent heart failure.

Vitamin D3 alleviates inflammation in ulcerative colitis by activating the VDR-NLRP6 signaling pathway.

Inflammation is a key factor in the development of ulcerative colitis (UC). 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, VD3), as the major active ingredient of vitamin D and an anti-inflammatory activator, is closely related to the initiation and development of UC, but its regulatory mechanism remains unclear. In this study, we carried out histological and physiological analyses in UC patients and UC mice. RNA sequencing (RNA-seq), assays for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), chromatin immunoprecipitation (ChIP) assays and protein and mRNA expression were performed to analyze and identify the potential molecular mechanism in UC mice and lipopolysaccharide (LPS)-induced mouse intestinal epithelial cells (MIECs). Moreover, we established nucleotide-binding oligomerization domain (NOD)-like receptor protein nlrp6 -/- mice and siRNA-NLRP6 MIECs to further characterize the role of NLRP6 in anti-inflammation of VD3. Our study revealed that VD3 abolished NOD-like receptor protein 6 (NLRP6) inflammasome activation, suppressing NLRP6, apoptosis-associated speck-like protein (ASC) and Caspase-1 levels via the vitamin D receptor (VDR). ChIP and ATAC-seq showed that VDR transcriptionally repressed NLRP6 by binding to vitamin D response elements (VDREs) in the promoter of NLRP6, impairing UC development. Importantly, VD3 had both preventive and therapeutic effects on the UC mouse model via inhibition of NLRP6 inflammasome activation. Our results demonstrated that VD3 substantially represses inflammation and the development of UC in vivo. These findings reveal a new mechanism by which VD3 affects inflammation in UC by regulating the expression of NLRP6 and show the potential clinical use of VD3 in autoimmune syndromes or other NLRP6 inflammasome-driven inflammatory diseases.

[Corrigendum] Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice.

Following the publication of this article, an interested reader drew to our attention that we had incorrectly reported (in the Materials and methods section, 'Western blot analysis', on p. 674) that the anti-farnesoid X receptor (FXR) antibody of Cell Signalling Technology, Inc., cat. no. #12295, had been used in this study to probe for FXR. In fact, the antibodies used in the above-mentioned study were a gift from the group of Dr Xin-Liang Ma at Thomas Jefferson University (Philadelphia, PA, USA), as referenced in the following article: [Pul J, Yuan A, Shan P, Gao E, Wang X, Wang Y, Lau WB, Koch W, Xin-Ma XL and He B: Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury. Eur Heart J 34: 1834-1845, 2013]. The antibody that was used for the western blotting analysis was raised against the C-terminus of FXR (C-20; cat. no. sc-1204, Santa Cruz Biotechnology, San Diego, CA, USA). We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. The error made in our incorrect referencing of the antibody did not affect the conclusions reported in this study. Furthermore, we regret the inconvenience that this mistake caused. [the original article was published in the Molecular Medicine Reports 16: 673-679, 2017; DOI: 10.3892/mmr.2017.6643].

Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice.

The farnesoid X receptor (FXR) is implicated in cholesterol and bile acid homeostasis; however, its role following myocardial infarction (MI) has yet to be elucidated. The aim of the present study was to investigate the effects of FXR knockout on left ventricular (LV) remodeling following MI. Coronary arteries of wild type (WT) and FXR­/­ mice were permanently occluded to cause MI, and serial echocardiographic and histological tests were conducted. At 4 weeks post­MI, FXR­/­ mice exhibited significantly smaller infarct sizes (34.20±2.58 vs. 44.20±3.19%), improved ejection fraction (47.31±1.08 vs. 37.64±0.75%) and reduced LV chamber dilation compared with WT mice. LV remodeling was significant as early as 7 days post­MI in FXR­/­ compared with WT mice. Histological features associated with enhanced long­term remodeling and improved functionality, such as increased angiogenesis via detection of CD31 and reduced fibrosis, were observed in the FXR­/­ group. Myocyte apoptosis within the infarcted zones appeared significantly reduced by day 7 in FXR­/­ mice. In conclusion, the results of the present study suggested that FXR knockout may participate in the preservation of post­MI cardiac functionality, via reducing fibrosis and chronic apoptosis, and ameliorating ventricular function.

Mesenchymal stem cells overexpressing integrin-linked kinase attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions.

Mesenchymal stem cells (MSCs) transfected by integrin-linked kinase (ILK) transplantation may improve the function and compliance of the post-infarct cardiac ventricle. We investigated the effect of ILK-modified MSC contiditioned medium (ILK-MSC-CM) on the proliferation of cardiac fibroblasts (CFBs) and collagen synthesis in vitro and in vivo. Myocardial infarction (MI)-induced animals received mesenchymal stem cell conditioned medium (MSC-CM), ILK-MSC-CM, or complete medium alone, subepicardially. A group of animals with MI and no other former intervention served as controls. ILK-MSC-CM inhibited CFB proliferation, reduced the gene expression of type I (Col1a1) and type III collagen (Col3a1), tissue inhibitors of metalloproteinase­1 (TIMP-1) and ­2 (TIMP-2), α smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). It also increased the gene expression of matrix metalloproteinase­2 (MMP­2) and -9 (MMP­9), as measured by qRT-PCR. Four weeks after the left anterior descending (LAD) coronary artery ligation, echocardiographic analysis demonstrated preserved cardiac geometry and contractility in the ILK-MSC-CM treated animals. Decreased infarct size and reduced fibrosis were observed in the ILK-MSC-CM group. Overexpression of ILK regulates paracrine actions of MSCs, and ILK-MSC-CM attenuates CFB proliferation and collagen synthesis through paracrine actions in vitro and in vivo.