2-undecanone protects against fine particles-induced heart inflammation via modulating Nrf2/HO-1 and NF-κB pathways.

Exposure to air pollution has been closely associated with some cardiovascular disease. One of the mechanisms of PM2.5 -mediated heart injury may be to promote inflammation. We aim to investigate whether the main extract of Houttuynia cordata, 2-undecanone, can prevent the inflammation caused by PM2.5 , and to reveal the underlying mechanisms. The results showed that PM2.5 increased the expression of certain inflammatory cytokines, and caused oxidative damage in BALB/c mice and H9C2 cells. Supplementation with 2-undecanone attenuated this PM2.5 -induced inflammatory injury and oxidative damage. Further, we elucidated that the protective effect of 2-undecanone may be associated with NF-κB and Nrf2/HO-1 pathways. The NF-κB pathway was distinctly activated after treated by PM2.5 , which can be blocked by 2-undecanone, accompanied by increasing Nrf2 and HO-1 levels. To figure out the relationship between NF-κB and Nrf2/HO-1 pathways, we knocked down Nrf2 gene. NF-κB pathway proteins and downstream inflammatory cytokines were significantly increased after treatment with PM2.5 , while 2-undecanone could decrease expression of these proteins. In conclusion, it is possible that 2-undecanone can induce the expression of the antioxidant enzyme HO-1 by activating Nrf2, thereby reducing NF-κB pathway and inflammatory damage of mouse myocardium caused by PM2.5 exposure.

Probabilistic punishment and reward under rule of trust-based decision-making in continuous public goods game.

Altruistic punishment and reward have been proved to promote the evolution of cooperation in the public goods game(PGG), but the punishers and the rewarders have to pay a price for these behaviors and that results in overall loss of interest. In present work, probabilistic punishment and reward are introduced to PGG. Probabilistic punishment and reward mean that punishment and reward are executed with a certain probability. Although that will reduce unnecessary costs, occasional absence of execution can lead to distrust. Thus we focus on how to implement punishment and reward efficiently within the structured populations. Numerical simulations are performed and prove that probabilistic punishment and reward can promote the evolution of cooperation more effectively. Further researches indicate that there is an optimal executing probability to promote cooperation and maximize reduction of cost. In addition, when the unit cost is high, the PGG with probabilistic punishment and reward still helps the evolution of altruistic punishers and rewarders, thereby avoiding collapse of cooperation.

Learning Backtrackless Aligned-Spatial Graph Convolutional Networks for Graph Classification.

In this paper, we develop a novel backtrackless aligned-spatial graph convolutional network (BASGCN) model to learn effective features for graph classification. Our idea is to transform arbitrary-sized graphs into fixed-sized backtrackless aligned grid structures and define a new spatial graph convolution operation associated with the grid structures. We show that the proposed BASGCN model not only reduces the problems of information loss and imprecise information representation arising in existing spatially-based graph convolutional network (GCN) models, but also bridges the theoretical gap between traditional convolutional neural network (CNN) models and spatially-based GCN models. Furthermore, the proposed BASGCN model can both adaptively discriminate the importance between specified vertices during the convolution process and reduce the notorious tottering problem of existing spatially-based GCNs related to the Weisfeiler-Lehman algorithm, explaining the effectiveness of the proposed model. Experiments on standard graph datasets demonstrate the effectiveness of the proposed model.

Patulin induces pyroptosis through the autophagic-inflammasomal pathway in liver.

Patulin (PAT), a kind of mycotoxin, is produced by many common fungi in fruit and vegetable-based products. It has been shown to cause hepatotoxicity. However, the possible mechanisms are not completely elucidated. The present study aimed to characterize the role of autophagic-inflammasomal pathway on pyroptosis induced by PAT. In mouse livers, PAT induced pyroptosis, and increased inflammation through the activation of NLRP3 inflammasome. In liver cells, we noticed that PAT induced pyroptotic cell death, which was confirmed by the activation of GSDMD, caspase-1, the release of LDH, and the result of PI/Hoechst assay. In addition, PAT-induced pyroptosis was dependent upon the activation of NLRP3 inflammasome and the release of cathepsin B. Cells had less expression of caspase-1 and IL-1ß protein levels after treated by NLRP3 inhibitor MCC950 or cathepsin B inhibitor CA-074Me. The expression of GSDMD and IL-1ß protein levels were also decrease after treated by caspase-1 inhibitor Ac-YVAD-cmk. Moreover, autophagy inhibitor 3-methyladenine (3-MA) attenuated PAT-induced increase in cytoplasmic cathepsin B expression, and subsequent LDH release, the activation of NLRP3 inflamosomes, pyroptotic cell death, and inflammation. These findings suggested that PAT-induced pyroptosis maybe through autophagy-cathepsin B-inflammasomal pathway in the liver. These results provide new mechanistic insights into PAT-induced hepatotoxicity.

Downregulation of natriuretic peptide clearance receptor mRNA in vascular smooth muscle cells by angiotensin II.

Angiotensin II can downregulate atrial natriuretic peptide binding to rat vascular smooth muscle cells (VSMCs), but the mechanism is not known. Because protein kinase C (PKC) mimetic phorbol myristate acetate (PMA) can destabilize natriuretic peptide clearance receptor (NPR-C) mRNA and angiotensin II activates several PKC isoforms in VSMCs, we hypothesized that angiotensin II treatment decreases NPR-C mRNA stability and exerts this effect through PKC. This study demonstrated that angiotensin II induced time- and concentration-dependent downregulation of NPR-C, which was completely inhibited by an angiotensin II type I receptor blocker losartan. NPR-C mRNA disappearance rate over 6 h was nearly doubled by exposure of VSMCs to 100 nm angiotensin II, compared with that observed after inhibition of RNA synthesis alone. However, this response to angiotensin II was undiminished by the PKC inhibitor chelerythrine, or by depletion of PKC by prior exposure of cells to PMA for 48 h. Inhibitors of tyrosine kinases, phospholipase C, or mitogen-activated protein kinase kinase also failed to reverse the angiotensin II effect. We conclude that at least two distinct proximal signaling pathways, one involved and one independent of phorbol ester-sensitive protein kinase C, lead to downregulation of NPR-C gene expression by destabilizing its mRNA.