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Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM. [Display omitted] [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is widely used and has been implicated in hepatotoxicity, although the mechanism is unclear. Here, we investigated the effect of DEHP on hepatic cholesterol metabolism in SD rats exposed to 0 and 300 mg/kg/day DEHP for 12 weeks. An RNA-Seq analysis was performed to describe the hepatic responses to long-term DEHP exposure in combination with serological and oxidative stress parameter measurements. DEHP increased the serum levels of total cholesterol (TC), high-density lipoprotein (HDL), and alanine transaminase (ALT). Moreover, DEHP increased the content of malondialdehyde (MDA) and decreased antioxidant enzyme activities in the liver. Transcriptomic results revealed that DEHP dramatically changed the cholesterol metabolism pathway and oxidation-reduction process and depressed gene expression involved in cholesterol efflux and monooxygenase activity. Total antioxidant capacity (T-AOC) positively correlated with Abcg5 and Abcg8. Overall, this study showed the mechanisms underlying hepatotoxicity caused by DEHP, providing new insights into understanding DEHP poisoning. • Effects of DEHP on the transcriptome in liver were studied. • DEHP increased cholesterol and HDL-C in serum. • Transcriptomics data revealed DEHP affected genes related to cholesterol efflux. • DEHP induced oxidative damage in rat liver. • DEHP caused disturbed cholesterol homeostasis contributed to oxidative stress. [ABSTRACT FROM AUTHOR]

[Display omitted] In this study, we introduced a white-light solid solution of RE-MOF, namely Tb 0.042 Eu 0.050 Y 0.908 -PTC (H 3 PTC=2, 4, 6-pyridine tricarboxylic acid), which exhibits outstanding chemical and thermal stability along with multiband luminescence. Luminescent sensing experiments demonstrate that Tb 0.042 Eu 0.050 Y 0.908 -PTC, as a multi-response luminescent sensor, has low detection limits for detecting Fe3+, Norfloxacin (NFX) and Ciprofloxacin (CPFX) via luminescence color changes. These results highlight their potential for luminescent sensing applications. Furthermore, the mechanism of luminescence sensing was investigated by powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS) and ultraviolet–visible (UV–vis) spectroscopy. [ABSTRACT FROM AUTHOR]

Foundation soil is an important medium for vibration wave propagation in the running of metro train. The spatial variability of soil properties has an important influence on vibration response. The parameters of foundation soil are often determined. Based on the probability density evolution method (PDEM) and stochastic field theory, a coupling model of the metro train-track-shield tunnel-foundation soil is established. The stochastic field is expressed by the series of stochastic variables and deterministic space functions by the Karhunen-Loeve Expansion (KLE) method. The stochastic parameters of the cross-section of tunnel-foundation soil are specified to simulate the stochastic field of foundation soil. Based on PDEM, the environmental vibration caused by metro trains in shield tunnels is studied. The results of ground surface vibration displacement under different metro train speeds are analyzed, and the upper and lower limits and probability density information of ground surface vibration displacement are obtained. The results show that the probability density distribution of ground vibration displacement at each time is approximately normal due to the stochastic field of foundation soil. The peak and valley of the vibration displacement curve at the inverted arch of the tunnel are caused by the wheel distance of the metro train. The probability density distribution of velocity and acceleration is more sensitive to the stochastic field of velocity foundation soil and the change in metro train speed. The maximum Z vibration level results under different metro train speeds all meet the requirements of vibration allowable limits in the specification. [ABSTRACT FROM AUTHOR]

Abstract: Twenty 13,28-epoxy and related triterpenoid saponins from Ardisia japonica were evaluated for their anti-proliferative activity on human liver cancer cells and normal liver cells. Eight saponins selectively inhibited the growth of liver cancer Bel-7402 and HepG-2 cells without affecting the survival of normal liver HL-7702 cells. The structure–activity relationship analyses indicated that the 13,28-epoxy, 16α-hydroxy, and C-30 methyl moieties in the sapogenin parts and the glycosyl moiety consisting from tetra- to hepta-saccharide units are important for this activity. Among the active saponins, ardisianoside B (2) and 3β-O-β-d-glucopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyl-13β,28-epoxy-16α-hydroxyoleanane (3) showed the most potent anti-proliferative activity against Bel-7402 cells in a dose- and time-dependent manner. The selective anti-proliferative activity is attributed to the different cellular responses (CDKs and cyclins levels, cell cycle arrest and apoptosis) between tumor and normal liver cells. Exposure to 2 and 3 selectively led to cell cycle arrest and apoptosis in Bel-7402 cells together with the increased pro-apoptotic caspase-8 and the decreased anti-apoptotic Cdc25A levels. [Copyright &y& Elsevier]