The mechanistic target of rapamycin complex 1 (mTORC1) signaling is the prototypical pathway regulating protein synthesis and cell proliferation. The level of mTORC1 activity is high in intestinal stem cells located at the base of the crypts and thought to gradually decrease as transit-amplifying cells migrate out of the crypts and differentiate into enterocytes, goblet cells or enteroendocrine cells along the epithelium. The unknown mechanism responsible for the silencing of intestinal epithelium mTORC1 during cell differentiation was investigated in Caco-2 cells, which spontaneously differentiate into enterocytes in standard growth medium. The results show that TSC2, an upstream negative regulator of mTORC1 was central to mTORC1 silencing in differentiated Caco-2 cells. AMPK-mediated activation of TSC2 (Ser1387) and repression of Raptor (Ser792), an essential component of mTORC1, were stimulated in differentiated Caco-2 cells. ERK1/2-mediated repression of TSC2 (Ser664) seen in undifferentiated Caco-2 cells was lifted in differentiated cells. IRS-1-mediated activation of AKT (Thr308) phosphorylation was stimulated in differentiated Caco-2 cells and may be involved in cross-pathway repression of ERK1/2. Additionally, PRAS40 (Thr246) phosphorylation was decreased in differentiated Caco-2 cells compared to undifferentiated cells allowing dephosphorylated PRAS40 to displace Raptor thereby repressing mTORC1 kinase activity.The NLRP3 inflammasome is a critical component of the innate immune response to sterile inflammation. Its regulation involves a priming step, required for up-regulation of inflammasome protagonists and an activation step leading to NLRP3 inflammasome complex assembly, which triggers caspase-1 activity. The IκKβ kinase regulates canonical NF-κB, a key pathway involved in transcriptional priming. We found that IκKβ also regulates the activation and function of the NLRP3 inflammasome beyond the priming step. Two unrelated IκKβ inhibitors, AFN700 and TPCA-1, when applied after priming, fully blocked IL-1β secretion triggered by nigericin in THP-1 cells. Both inhibitors prevented neither inflammasome assembly, as monitored by measuring the formation of ASC specks, nor the generation of caspase-1 p20, a hallmark of caspase-1 activity, but they impaired the initial cleavage and activation of procaspase-1. These data thus indicate that IκKβ activity is required for efficient activation of NLRP3, suggesting that IκKβ may fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome.Ni/diamond composite coatings have been synthesized by ultrasonic-assisted electrodeposition in a Ni electroplating bath containing diamond nanoparticles. The influences of current density and ultrasonic agitation on the coating composition, morphology, topography, phase structure, and electrochemical characteristics of the electrodeposits were evaluated. Ultrasonic agitation was provided using an external ultrasonic bath at a frequency of 40 kHz and acoustic power of 300 W. Coating samples were also prepared under magnetic stirring for comparison with the ultrasonic-assisted deposits. This work reveals that the diamonds have been incorporated and evenly distributed in the composites. The coatings exhibit dense, granular like morphology with pyramid-like grains. As current density increases, the diamond amount of ultrasonic-assisted electrodeposits first increased to maximum of 11.4 wt% at 3 A dm-2 and then decreases to 9.9 wt% at 5 A dm-2, and the RTC of the preferred orientation (200) plane increases from 76.3% up to 93.4%. The crystallite size was 60-80 nm and the Ra of the magnetic and ultrasonic agitations were 116 nm, 110 nm, respectively. The maximum Rp of 39.9, 50.3 kΩ cm2 was obtained at 4 A dm-2 when respectively immersed 30 min and 7 days, illustrating the best corrosion resistance of the coatings of 4 A dm-2. The effects of mechanical and ultrasonic agitations on the mechanism of the co-electrodeposition process were both proposed. The incorporation of diamond particles enhances the hardness and wear-resisting property of the electrodeposits. The ultrasonic-assisted electrodeposited Ni/diamond coating has better corrosion resistance than that prepared under mechanical stirring conditions.
  Liver diseases are currently common disorders worldwide. Especially, the proportion of patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is growing globally. An increasing number of studies have revealed a close relationship between the intestinal microbiota and the development of NAFLD and ALD. A better understanding of the role of intestinal microbiota and the intestine-liver axis thus might lead to the development novel therapies for the treatment of these diseases.
 Liver diseases are currently common disorders worldwide. Especially, the proportion of patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is growing globally. An increasing number of studies have revealed a close relationship between the intestinal microbiota and the development of NAFLD and ALD. A better understanding of the role of intestinal microbiota and the intestine-liver axis thus might lead to the development novel therapies for the treatment of these diseases.All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins.  https://www.selleckchem.com/products/nvp-bgt226.html  The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method.