Vasoprotection by Dietary Supplements and Exercise: Role of TNFα Signaling

Vascular dysfunction contributes to the pathogenesis of various cardiovascular diseases. Dietary supplements, including fish oil, dietary fibers, and various natural products, and exercise training exert vasoprotective effects. However, the mechanisms underlying the vasoprotective benefits of dietary supplements and physical activity demand extensive investigation. Accumulating evidence suggests that inflammatory cytokine tumor necrosis factor-alpha (TNFα) plays a pivotal role in the dysregulation of macrovascular and microvascular function. TNFα induces vascular inflammation, monocyte adhesion to endothelial cells, vascular oxidative stress, apoptosis, and atherogenic response and participates in the regulation of thrombosis and coagulation through multiple signaling pathways involving NFκB, Sp1, activator protein 1, JNK, p38, STAT3, and so forth. Dietary supplements and exercise training decrease TNFα production and ameliorate TNFα-mediated pathological changes in vasculature. Thus, the inhibitory effects of dietary supplements and physical exercise on TNFα production and TNFα signaling may contribute to their vasoprotective properties

Calculation of oxygen diffusion coefficients in oxide films formed on low-temperature annealed Zr alloys and their related corrosion behavior

The growth of oxide film, which results from the inward oxygen diffusion from a corrosive environment, is a critical consideration for the corrosion resistance of zirconium alloys. This work calculates the oxygen diffusion coefficients in the oxide films formed on zirconium alloys annealed at 400~500 °C and investigates the related corrosion behavior. The annealed samples have a close size for the second-phase particles but a distinctive hardness, indicating the difference in substrate conditions. The weight gain of all samples highly follows parabolic laws. The weight gain of the sample annealed at 400 °C has the fastest increase rate at the very beginning of the corrosion test, but its oxide film has the slowest growth rate as the corrosion proceeds. By contrast, the sample annealed at 500 °C shows the lowest weight gain but the highest corrosion rate constant. Such a corrosion behavior is attributed to the amount of defects existing in the oxide film formed on the annealed samples; fewer defects would provide a lower fraction of short-circuit diffusion in total diffusion, resulting in a lower diffusion coefficient of oxygen in the oxide film, thereby producing better corrosion resistance. This is consistent with the calculated diffusion coefficients of oxygen in the oxide films: 3.252 × 10−11 cm2/s, 3.464 × 10−11 cm2/s and 3.740 × 10−11 cm2/s for the samples annealed at 400 °C, 450 °C, and 500 °C, respectively

Direct relationship between levels of TNF-α expression and endothelial dysfunction in reperfusion injury

We previously found that myocardial ischemia/ reperfusion (I/R) initiates expression of tumor necrosis factor-α (TNF) leading to coronary endothelial dysfunction. However, it is not clear whether there is a direct relationship between levels of TNF expression and endothelial dysfunction in reperfusion injury. We studied levels of TNF expression by using different transgenic animals expressing varying amounts of TNF in I/R. We crossed TNF overexpression (TNF++/++) with TNF knockout (TNF-/-) mice; thus we have a heterozygote population of mice with the expression of TNF "in between" the TNF-/- and TNF++/++ mice. Mouse hearts were subjected to 30 min of global ischemia followed by 90 min of reperfusion and their vasoactivity before and after I/R was examined in wild type (WT), TNF-/-, TNF++/++ and TNF heterozygote (TNF -/++, cross between TNF-/- and TNF++/++) mice. In heterozygote TNF-/++ mice with intermediate cardiac-specific expression of TNF, acetyl-choline-induced or flow-induced endothelial-dependent vasodilation following I/R was between TNF++/++ and TNF-/- following I/R. Neutralizing antibodies to TNF administered immediately before the onset of reperfusion-preserved endothelial-dependent dilation following I/R in WT, TNF-/++ and TNF++/++ mice. In WT, TNF -/++ and TNF++/++ mice, I/R-induced endothelial dysfunction was progressively lessened by administration of free-radical scavenger TEMPOL immediately before initiating reperfusion. During I/R, production of superoxide (O2-) was greatest in TNF ++/++ mice as compared to WT, TNF-/++ and TNF -/- mice. Following I/R, arginase mRNA expression was elevated in the WT, substantially elevated in the TNF-/++ and TNF ++/++mice and not affected in the TNF-/- mice. These results suggest that the level of TNF expression determines arginase expression in endothelial cells during myocardial I/R, which is one of the mechanisms by which TNF compromises coronary endothelial function in reperfusion injury

Weakly Supervised Semantic Segmentation for Large-Scale Point Cloud

Existing methods for large-scale point cloud semantic segmentation require expensive, tedious and error-prone manual point-wise annotations. Intuitively, weakly supervised training is a direct solution to reduce the cost of labeling. However, for weakly supervised large-scale point cloud semantic segmentation, too few annotations will inevitably lead to ineffective learning of network. We propose an effective weakly supervised method containing two components to solve the above problem. Firstly, we construct a pretext task, \textit{i.e.,} point cloud colorization, with a self-supervised learning to transfer the learned prior knowledge from a large amount of unlabeled point cloud to a weakly supervised network. In this way, the representation capability of the weakly supervised network can be improved by the guidance from a heterogeneous task. Besides, to generate pseudo label for unlabeled data, a sparse label propagation mechanism is proposed with the help of generated class prototypes, which is used to measure the classification confidence of unlabeled point. Our method is evaluated on large-scale point cloud datasets with different scenarios including indoor and outdoor. The experimental results show the large gain against existing weakly supervised and comparable results to fully supervised methods\footnote{Code based on mindspore: https://github.com/dmcv-ecnu/MindSpore\_ModelZoo/tree/main/WS3\_MindSpore}

Role of TNF-α in vascular dysfunction

Healthy vascular function is primarily regulated by several factors including EDRF (endothelium-dependent relaxing factor), EDCF (endothelium-dependent contracting factor) and EDHF (endothelium-dependent hyperpolarizing factor). Vascular dysfunction or injury induced by aging, smoking, inflammation, trauma, hyperlipidaemia and hyperglycaemia are among a myriad of risk factors that may contribute to the pathogenesis of many cardiovascular diseases, such as hypertension, diabetes and atherosclerosis. However, the exact mechanisms underlying the impaired vascular activity remain unresolved and there is no current scientific consensus. Accumulating evidence suggests that the inflammatory cytokine TNF (tumour necrosis factor)-α plays a pivotal role in the disruption of macrovascular and microvascular circulation both in vivo and in vitro. AGEs (advanced glycation end-products)/RAGE (receptor for AGEs), LOX-1 [lectin-like oxidized low-density lipoprotein receptor-1) and NF-κB (nuclear factor κB) signalling play key roles in TNF-α expression through an increase in circulating and/or local vascular TNF-α production. The increase in TNF-α expression induces the production of ROS (reactive oxygen species), resulting in endothelial dysfunction in many pathophysiological conditions. Lipid metabolism, dietary supplements and physical activity affect TNF-α expression. The interaction between TNF-α and stem cells is also important in terms of vascular repair or regeneration. Careful scrutiny of these factors may help elucidate the mechanisms that induce vascular dysfunction. The focus of the present review is to summarize recent evidence showing the role of TNF-α in vascular dysfunction in cardiovascular disease. We believe these findings may prompt new directions for targeting inflammation in future therapies