Interleukin-18 enhances vascular calcification and osteogenic differentiation of vascular smooth muscle cells through TRPM7 channel activation

Objective—Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is a key mechanism of VC. Recent studies show that IL-18 (interleukin-18) favors VC while TRPM7 (transient receptor potential melastatin 7) channel upregulation inhibits VC. However, the relationship between IL-18 and TRPM7 is unclear. We questioned whether IL-18 enhances VC and osteogenic differentiation of VSMCs through TRPM7 channel activation. Approach and Results—Coronary artery calcification and serum IL-18 were measured in patients by computed tomographic scanning and enzyme-linked immunosorbent assay, respectively. Primary rat VSMCs calcification were induced by high inorganic phosphate and exposed to IL-18. VSMCs were also treated with TRPM7 antagonist 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA to block TRPM7 channel activity and expression. TRPM7 currents were recorded by patch-clamp. Human studies showed that serum IL-18 levels were positively associated with coronary artery calcium scores (r=0.91; P<0.001). In VSMCs, IL-18 significantly decreased expression of contractile markers α-smooth muscle actin, smooth muscle 22 α, and increased calcium deposition, alkaline phosphatase activity, and expression of osteogenic differentiation markers bone morphogenetic protein-2, Runx2, and osteocalcin (P<0.05). IL-18 increased TRPM7 expression through ERK1/2 signaling activation, and TRPM7 currents were augmented by IL-18 treatment. Inhibition of TRPM7 channel by 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA prevented IL-18–enhanced osteogenic differentiation and VSMCs calcification. Conclusions—These findings suggest that coronary artery calcification is associated with increased IL-18 levels. IL-18 enhances VSMCs osteogenic differentiation and subsequent VC induced by β-glycerophosphate via TRPM7 channel activation. Accordingly, IL-18 may contribute to VC in proinflammatory conditions

The residential coal consumption : disparity in urban-rural China

We appreciate the support of the Program for Major Projects in Philosophy and Social Science Research of the Ministry of Education of China (No. 14JZD031), Key Program of National Social Science Fund of China (No. 15AJY005), National Natural Science Foundation of China (Nos. 71473203, 71171001, and 71471001), and New Century Excellent Talents in University (No. NCET-12-0595).Peer reviewedPostprin

A survey on adaptive random testing

Random testing (RT) is a well-studied testing method that has been widely applied to the testing of many applications, including embedded software systems, SQL database systems, and Android applications. Adaptive random testing (ART) aims to enhance RT's failure-detection ability by more evenly spreading the test cases over the input domain. Since its introduction in 2001, there have been many contributions to the development of ART, including various approaches, implementations, assessment and evaluation methods, and applications. This paper provides a comprehensive survey on ART, classifying techniques, summarizing application areas, and analyzing experimental evaluations. This paper also addresses some misconceptions about ART, and identifies open research challenges to be further investigated in the future work

The expression profile analysis of NKX2-5 knock-out embryonic mice to explore the pathogenesis of congenital heart disease

AbstractBackgroundMutation of NKX2-5 could lead to the development of congenital heart disease (CHD) which is a common inherited disease. This study aimed to investigate the pathogenesis of CHD in NKX2-5 knock-out embryonic mice.MethodsThe expression profile in the NKX2-5 knock-out embryonic mice (GSE528) was downloaded from Gene Expression Omnibus. The heart tissues from the null/heterozygous embryonic day 12.5 mice were compared with wild-type mice to identify differentially expressed genes (DEGs), and then DEGs corresponding to the transcriptional factors were filtered out based on the information in the TRANSFAC database. In addition, a transcriptional regulatory network was constructed according to transcription factor binding site information from the University of California Santa Cruz database. A pathway interaction network was constructed by latent pathways identification analysis.ResultsThe 42 DEGs corresponding to transcriptional factors from the null and heterozygous embryos were identified. The transcriptional regulatory networks included five down-regulated DEGs (SP1, SRY, JUND, STAT6, and GATA6), and six up-regulated DEGs [POU2F1, NFY (NFYA/NFYB/NFYC), USF2 and MAX]. Latent pathways analysis demonstrated that ribosome, glycolysis/gluconeogenesis, and dilated cardiomyopathy pathways significantly interacted.ConclusionThe identified DEGs and latent pathways could provide new comprehensive view for understanding the pathogenesis of CHD

MyoPS-Net: Myocardial Pathology Segmentation with Flexible Combination of Multi-Sequence CMR Images

Myocardial pathology segmentation (MyoPS) can be a prerequisite for the accurate diagnosis and treatment planning of myocardial infarction. However, achieving this segmentation is challenging, mainly due to the inadequate and indistinct information from an image. In this work, we develop an end-to-end deep neural network, referred to as MyoPS-Net, to flexibly combine five-sequence cardiac magnetic resonance (CMR) images for MyoPS. To extract precise and adequate information, we design an effective yet flexible architecture to extract and fuse cross-modal features. This architecture can tackle different numbers of CMR images and complex combinations of modalities, with output branches targeting specific pathologies. To impose anatomical knowledge on the segmentation results, we first propose a module to regularize myocardium consistency and localize the pathologies, and then introduce an inclusiveness loss to utilize relations between myocardial scars and edema. We evaluated the proposed MyoPS-Net on two datasets, i.e., a private one consisting of 50 paired multi-sequence CMR images and a public one from MICCAI2020 MyoPS Challenge. Experimental results showed that MyoPS-Net could achieve state-of-the-art performance in various scenarios. Note that in practical clinics, the subjects may not have full sequences, such as missing LGE CMR or mapping CMR scans. We therefore conducted extensive experiments to investigate the performance of the proposed method in dealing with such complex combinations of different CMR sequences. Results proved the superiority and generalizability of MyoPS-Net, and more importantly, indicated a practical clinical application

Short-chain Fatty Acids Regulate the Immune Responses via G Protein Coupled Receptor 41 in Bovine Rumen Epithelial Cells

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Maternal Dietary Patterns and Pregnancy Outcome

Abstract: Maternal nutritional status during pregnancy will affect the outcomes for the mother and the baby. Many analyses of the relationship between diet and outcome are often based on a single or a few food items or nutrients. However, foods are not consumed in isolation and dietary patterns can be used to assess the whole diet consumed. The use of dietary pattern analysis to understand nutritional intake and pregnancy outcome is becoming more and more popular. Many published studies have showed the association between maternal dietary patterns and pregnancy outcome. This review examined articles about the relationship between maternal dietary patterns and pregnancy outcome. As a modifiable factor, dietary patterns may be more applicable to clinical and pregnant health interventions