MLKL promotes hepatocarcinogenesis through inhibition of AMPK-mediated autophagy.

The pseudokinase mixed lineage kinase domain-like (MLKL) is an essential component of the activation of the necroptotic pathway. Emerging evidence suggests that MLKL plays a key role in liver disease. However, how MLKL contributes to hepatocarcinogenesis has not been fully elucidated. Herein, we report that MLKL is upregulated in a diethylnitrosamine (DEN)-induced murine HCC model and is associated with human hepatocellular carcinomas. Hepatocyte-specific MLKL knockout suppresses the progression of hepatocarcinogenesis. Conversely, MLKL overexpression aggravates the initiation and progression of DEN-induced HCC. Mechanistic study reveals that deletion of MLKL significantly increases the activation of autophagy, thereby protecting against hepatocarcinogenesis. MLKL directly interacts with AMPKα1 and inhibits its activity independent of its necroptotic function. Mechanistically, MLKL serves as a bridging molecule between AMPKα1 and protein phosphatase 1B (PPM1B), thus enhancing the dephosphorylation of AMPKα1. Consistently, MLKL expression correlates negatively with AMPKα1 phosphorylation in HCC patients. Taken together, our findings highlight MLKL as a novel AMPK gatekeeper that plays key roles in inhibiting autophagy and driving hepatocarcinogenesis, suggesting that the MLKL-AMPKα1 axis is a potential therapeutic target for HCC.

10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation.

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1ß secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.

Preparation of a sulfonated coal@ZVI@chitosan-acrylic acid composite and study of its removal of groundwater Cr(VI).

In this research, a new composite adsorbent (SC@ZVI@CS-AA) was designed and synthesized, and its application for the removal of Cr(VI) in groundwater was investigated. The interaction between SC@ZVI@CS-AA and Cr(VI) conformed to a pseudo-second-order model, and the adsorption process was dominated by chemisorption. The effects of material ratios, pH, temperature, SC@ZVI@CS-AA dosage, and coexisting ions on the removal of Cr(VI) were investigated. The removal efficiency of Cr(VI) by SC@ZVI@CS-AA reached 95%, and the reaction was significantly inhibited when SO42- was present. Thermodynamically, the adsorption of Cr(VI) proceeded spontaneously above 35 °C (ΔGθ < 0). According to scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectrometry, and synchronous thermal analysis, the removal mechanism of Cr(VI) by SC@ZVI@CS-AA was attributed to electrostatic attraction and reduction. In addition, SC@ZVI@CS-AA had good cyclic adsorption performance. Overall, the SC@ZVI@CS-AA composite showed great potential in the remediation of Cr(VI)-contaminated groundwater.

Multiresidue Analysis of Pesticides in Straw Roughage by Liquid Chromatography-Tandem Mass Spectrometry.

A multiresidue analytical method using a modification of the "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) sample preparation approach combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was established and validated for the rapid determination of 69 pesticides at different levels (1-100 ng/g) in wheat and rice straws. In the quantitative analysis, the recoveries ranged from 70 to 120%, and consistent RSDs ≤ 20% were achieved for most of the target analytes (53 pesticides in wheat straw and 58 in rice straw). Almost all of the analytes achieved good linearity with R(2) > 0.98, and the limit of validation levels (LVLs) for diverse pesticides ranged from 1 to 10 ng/g. Different extraction and cleanup conditions were evaluated in both types of straw, leading to different options. The use of 0.1% formic acid or not in extraction with acetonitrile yielded similar final outcomes, but led to the use of a different sorbent in dispersive solid-phase extraction. Both options are efficient and useful for the multiresidue analysis of targeted pesticides in wheat and rice straw samples.

Dissipation dynamics and final residues of cloransulam-methyl in soybean and soil.

This work is the first report on the dissipation and final residue of cloransulam-methyl on soybean plant at field conditions. A fast, simple, and reliable residue analytical method for determination of cloransulam-methyl in soybean matrices and soil was developed based on quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection. The average recoveries of cloransulam-methyl in soybean matrices and soil ranged from 80 to 105%, with RSDs between 3-11%. The limit of detection (LOD) was 0.001 mg kg(-1) for soybean grain, plant, and soil and was 0.005 mg kg(-1) for soybean straw. This method was then used to characterize dissipation of cloransulam-methyl in soybeans and soil from three locations in China for the first time. Cloransulam-methyl dissipated quickly in soybean plant with half-lives (T1/2) of 0.21-0.56 days. The dissipation dynamic in soil was characterized using both first-order kinetics model and two-compartment model, and the half-lives were similar, ranging from 0.44 to 5.53 days at three experimental sites in 2012 and 2013. The final residue data showed a very low level of cloransulam-methyl in soil (≤0.026 mg kg(-1)), soybean grain (≤0.001 mg kg(-1)), and straw (≤0.005 mg kg(-1)) samples at harvest time. With the faster and simple analytical method on soybean and soil, rapid dissipation of cloransulam-methyl was observed at three geospatial locations in China, and the terminal residue levels were negligible, so mammalian ingestion exposure is minimal.

Dissipation and residues of picoxystrobin in peanut and field soil by QuEChERS and HPLC-MS/MS.

The dissipation and final residues of picoxystrobin in peanut and soil were determined by a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The dissipation and final residue of picoxystrobin at three different provinces (Hebei, Hubei, and Shandong) in China were studied. The fortification experiments at three different spiking levels of 0.01, 0.05, and 0.5 mg kg(-1) in all matrices (soil, peanut seedling, shell, stalk, and kernels) were conducted, and the recoveries were 79-114% with relative standard deviations of 3-12 (n = 5). The dissipation half-lives of picoxystrobin were 1.5-8.6 days in soil, and 2.1-2.8 days in seedlings. The final residues of picoxystrobin in supervised field trials were 0.05-6.82 mg kg(-1) in stalk, ≤0.381 mg kg(-1) in soil, ≤0.069 mg kg(-1) in shells, and ≤0.005 mg kg(-1) in peanut kernels. Considering the final residue levels and the maximum residue limits (MRLs), the pre-harvest interval of 14 days was recommended for the safe use of picoxystrobin in peanut crop.

Determination and dissipation of fipronil and its metabolites in peanut and soil.

In this study, a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was established for the extraction and cleanup of fipronil and its three metabolites (fipronil solfone, sulfide, and desulfinyl) in peanut kernel, shell, straw, seedling, and soil samples, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for analysis. The average recoveries were 66-116% at the level of 0.001-0.1 mg/kg with the RSD <19%, and the limit of detection was 0.3 ng/g for all matrices. The dissipation experiment results demonstrated that fipronil dissipated more rapidly in peanut seedling than in soil, with half-lives of <1 day in peanut seedling and 32-57 days in soil depending on the soil pH. The final residues at harvest of peanut kernels were all below 0.02 mg/kg, whereas in peanut shell and straw, the total highest residues were 0.99 and 0.30 mg/kg, respectively. Fipronil-desulfinyl and fipronil-sulfone were the highest residue metabolites in peanut plant (seedling and straw) and soil samples, respectively.

Determination of halosulfuron-methyl residues and dissipation in wheat by QuEChERS and LC-MS/MS.

A sensitive and rapid analytical method based on QuEChERS (quick, easy, cheap, effective, rugged and safe) sample preparation and LC-MS/MS detection was developed for the analysis of halosulfuron-methyl residues in wheat. The recoveries of halosulfuron-methyl in both the wheat plant and grain ranged from 87% to 119% and from 75% to 97%, respectively, with relative standard deviations (RSDs) of 3-9%. The limit of quantification (LOQ) was 0.005 mg kg(-1) for wheat plant and 0.001 mg kg(-1) for wheat grain. The half-life of halosulfuron-methyl in the wheat plant was 0.9-9.5 days. The terminal residue levels of halosulfuron-methyl in wheat grain were below 0.01 mg kg(-1) at harvest.