Methylsulfonylmethane ameliorates metabolic-associated fatty liver disease by restoring autophagy flux via AMPK/mTOR/ULK1 signaling pathway

Introduction: Metabolism-associated fatty liver disease (MAFLD) is a global health concern because of its association with obesity, insulin resistance, and other metabolic abnormalities. Methylsulfonylmethane (MSM), an organic sulfur compound found in various plants and animals, exerts antioxidant and anti-inflammatory effects. Here, we aimed to assess the anti-obesity activity and autophagy-related mechanisms of Methylsulfonylmethane.Method: Human hepatoma (HepG2) cells treated with palmitic acid (PA) were used to examine the effects of MSM on autophagic clearance. To evaluate the anti-obesity effect of MSM, male C57/BL6 mice were fed a high-fat diet (HFD; 60% calories) and administered an oral dose of MSM (200 or 400 mg/kg/day). Moreover, we investigated the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin complex 1 (mTORC1)/UNC-51-like autophagy-activating kinase 1 (ULK1) signaling pathway to further determine the underlying action mechanism of MSM.Results: Methylsulfonylmethane treatment significantly mitigated PA-induced protein aggregation in human hepatoma HepG2 cells. Additionally, Methylsulfonylmethane treatment reversed the PA-induced impairment of autophagic flux. Methylsulfonylmethane also enhanced the insulin sensitivity and significantly suppressed the HFD-induced obesity and hepatic steatosis in mice. Western blotting revealed that Methylsulfonylmethane improved ubiquitinated protein clearance in HFD-induced fatty liver. Remarkably, Methylsulfonylmethane promoted the activation of AMPK and ULK1 and inhibited mTOR activity.Conclusion: Our study suggests that MSM ameliorates hepatic steatosis by enhancing the autophagic flux via an AMPK/mTOR/ULK1-dependent signaling pathway. These findings highlight the therapeutic potential of MSM for obesity-related MAFLD treatment

Catechol as a New Electron Hot Spot of Carbon Nitride

Graphitic carbon nitride (CNx) is a promising photocatalyst with visible-light sensitivity, attractive band-edge positions, tunable electronic structure, and eco-friendliness. However, their applications are limited by a low catalytic activity due to inefficient charge separation and insufficient visiblelight absorption. Here we show a new method to generate the electron polarization of CNx toward the edge via the chemical conjugation of catechol to CNx for enhanced photochemical activity. The electron-attracting property of catechol/quinone pairs induces the accumulation of photoexcited electrons at the edge of conjugated catechol-CNx hybrid nanostructure (Cat-CNx), , serving as an electron hot spot, as demonstrated by positive open-circuit photovoltage, which increases electron transfer through the conjugated catechol while suppressing charge recombination in the CNx. The catechol conjugation also widens the photoactive spectrum via the larger range delocalization of π-electrons. Accordingly, Cat-CNx reveals a 6.3 higher reductive photocurrent density than CNx. Gold ion reduction dramatically increased due to the enhanced electron transfer activity of Cat-CNx in cooperation with the inherent hydrophilicity and metal chelating property of catechols. Cat-CNx exhibits a 4.3 higher maximum adsorption capacity for gold ions under simulated sun light illumination compared to CNx. This work suggests that the post-modification of CNx’s π-conjugated system is a promising route to handle varied shortcomings and broaden availability of CNx

High temperature oxidation of the Zr-1Nb-1Sn-0.1Fe cladding tube at the temperatures of 1000 - 1200??C

So far, many experiments have been performed to study the performance of the Zirconium alloys during the accident condition, especially LOCA (Loss Of Coolant Accident) (Ref. 1,2,3). Most of the studies performed in the past are based on the experimental results which used Zry- 4 cladding specimens, but the studies which use recently developed zirconium alloys such as ZIRLO, M5, HANA are not many, and the results have some inconsistencies. In this study, high temperature corrosion tests were performed using Zr-1Nb-1Sn-0.1Fe cladding tube specimens. The experiments were performed at 1000-1200??C, the oxidation kinetics and the breakaway oxidation behavior were studied. The data on oxidation kinetics showed closer results with those from the tests by Westinghouse, but the minimum time for the breakaway oxidation was shorter comparing to the results from Westinghouse and ANL. And also, more detailed analysis results on oxidation kinetics and breakaway oxidation are included

Evaluation of Temporal Contribution of Groundwater to a Small Lake through Analyses of Water Quantity and Quality

Groundwater can flow into or out of surface water and thus can greatly affect the quantity and quality of surface water. In this study, we conducted a water quantity and quality analysis for 11 months in 2018 and 2019 to evaluate the temporal contribution of groundwater to surface water at Osongji, a small lake located in Jeonju-si, Jeollabuk-do, Korea. Groundwater fluxes and groundwater and surface water levels were measured using seepage meters and a piezometer, respectively. On-site water quality parameters, cations, and anions for groundwater and surface water were analyzed. Hydrogen and oxygen isotopes for groundwater, surface water, and rainwater were also analyzed. Groundwater influx did not correlate directly to precipitation, suggesting that it may be delayed after rainwater infiltration. Aqueous chemistry indicated that the hydrogeochemical characteristics of surface water were substantially affected by groundwater. The isotopic composition of surface water changed over time, indicating a different contribution of groundwater in different seasons. This study shows that water quantity and quality data can be used in combination to evaluate temporal changes in the groundwater contribution to surface water

Dexamethasone inhibits activation of monocytes/macrophages in a milieu rich in 27-oxygenated cholesterol.

Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol

Effects of dexamethasone (Dex) on CCL2 expression and monocytic cell migration.

<p>(A) Levels of CCL2 transcript were assessed by real-time PCR. The y-axis values represent increases in CCL2 mRNA levels normalized to GAPDH levels, relative to that of the non-treated THP-1 cells (control). Data are expressed as the means ± SD (n = 3 replicates for each group). (B) Culture media were isolated, and the levels of CCL2 protein in the media were measured by ELISA. Data are expressed as the means ± SD (n = 3 replicates for each group). (C) Monocytic cells were exposed to the conditioned media isolated above, and migration of monocytic cells was measured by chemotaxis assay. Data are expressed as the means ± SD (n = 3 replicates for each group). The results shown are the representative of three independent experiments. *** P < 0.001 vs. control; ** P < 0.01 vs. control; ### P < 0.001 vs. 27OHChol; ## P < 0.01 vs. 27OHChol.</p