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Alkylglycerol monooxygenase (AGMO) is a tetrahydrobiopterin (BH4)-dependent enzyme with major expression in the liver and white adipose tissue that cleaves alkyl ether glycerolipids. The present study describes the disclosure and biological characterization of a candidate compound (Cp6), which inhibits AGMO with an IC50 of 30-100 µM and 5-20-fold preference of AGMO relative to other BH4-dependent enzymes, i.e., phenylalanine-hydroxylase and nitric oxide synthase. The viability and metabolic activity of mouse 3T3-L1 fibroblasts, HepG2 human hepatocytes and mouse RAW264.7 macrophages were not affected up to 10-fold of the IC50. However, Cp6 reversibly inhibited the differentiation of 3T3-L1 cells towards adipocytes, in which AGMO expression was upregulated upon differentiation. Cp6 reduced the accumulation of lipid droplets in adipocytes upon differentiation and in HepG2 cells exposed to free fatty acids. Cp6 also inhibited IL-4-driven differentiation of RAW264.7 macrophages towards M2-like macrophages, which serve as adipocyte progenitors in adipose tissue. Collectively, the data suggest that pharmacologic AGMO inhibition may affect lipid storage.With the distinguished properties in electronics, thermal conductivity, optical transparence and mechanics, graphene has a powerful potential in nanosensors, nano-resonators, supercapacitors, batteries, etc. The resonant frequency of graphene is an important factor in its application and working environment. However, the random dispersed porosities in graphene evidently change the lattice structure and destroy the integrity and geometrical periodicity. This paper focuses on the effects of random porosities in resonant frequencies of graphene. Monte Carlo simulation is applied to propagate the porosities in the finite element model of pristine graphene. The statistical results and probability density distribution of porous graphene with atomic vacancy defects are computed based on the Monte Carlo finite element model. The results of porous graphene with atomic vacancy defects are compared and discussed with the results of graphene with bond vacancy defects. The enhancement effects of atomic vacancy defects are confirmed in porous graphene. The influences of atomic vacancy defects on displacement and rotation vector sums of porous graphene are more concentrated in local places.In this paper, the dynamic foaming process of micro-foaming polypropylene (PP) in different foaming environments in real time was obtained via a visualization device. The relationship curve between cell number (n) and foaming time (t) was plotted, and then the nucleation kinetics of foam cells was analyzed. Results showed that the formation rate of cells changed obviously with the variation of melt temperature and the content of the foaming agent. The n-t curves presented a typical "S" shape, which indicated that the appearance of the cell number increased slowly in the initial foaming period, then increased rapidly in a short time, and finally maintained a certain value. When a certain pressure was applied to the PP melt, the external force had a great influence on the n-t curve. With the increasing external force, the rate of cell formation increased rapidly, and the shape of the n-t curve changed from "S" to "semi-S" without an obvious slow increase. The investigation of the n-t relationship in the PP dynamic foaming process under different foaming environments could provide effective bases for improving the foaming quality of injection molding foaming materials.Food insecurity is an important contributor to health and a factor in both underweight and malnutrition, and overweight and obesity. Countries where both undernutrition and overweight and obesity coexist are said to be experiencing a double burden of malnutrition. India is one example of a country experiencing this double burden. Women have been found to experience the negative impacts of food insecurity and obesity, however, the reasons that women experience the impact of malnutrition more so than men are complex and are under-researched. This current research employed a mixed methods approach to begin to fill this gap by exploring the dietary intake, anthropometric characteristics, and food security status of rural Indian women. In total, 78 household were surveyed. The average waist measurement, waist to hip ratio, and BMI were all above WHO recommendations, with two thirds of participants categorized as obese. Contributing to these findings was a very limited diet, high in energy, and low in protein and iron. Navitoclax The findings of this research suggest that the rural Indian women in this study have a lack of diet diversity and may be at risk of a range of non-communicable diseases.Wear debris generated from the bearing surfaces of joint arthroplasties leads to acute and chronic inflammation, which is strongly associated with implant failure. Macrophages derived from monocytes recruited to the local tissues have a significant impact on bone healing and regeneration. Macrophages can adopt various functional phenotypes. While M1 macrophages are pro-inflammatory, M2 macrophages express factors important for tissue repair. Here, we established a 3D co-culture system to investigate how the immune system influences the osteogenic differentiation of mesenchymal stem cells (MSCs) in the presence of micron-sized particles. This system allowed for the simulation of an inflammatory reaction via the addition of Lipopolysaccharide-contaminated polyethylene particles (cPE) and the characterization of bone formation using micro-CT and gene and protein expression. Co-cultures of MSCs with M2 macrophages in the presence of cPE in a 3D environment resulted in the increased expression of osteogenic markers, suggesting facilitation of bone formation. In this model, the upregulation of M2 macrophage expression of immune-associated genes and cytokines contributes to enhanced bone formation by MSCs. This study elucidates how the immune system modulates bone healing in response to an inflammatory stimulus using a unique 3D culture system.Natural killer (NK) and dendritic cells (DCs) are innate immune cells that play a crucial role in anti-tumor immunity. NK cells kill tumor cells through direct cytotoxicity and cytokine secretion. DCs are needed for the activation of adaptive immune responses against tumor cells. Both NK cells and DCs are subdivided in several subsets endowed with specialized effector functions. Crosstalk between NK cells and DCs leads to the reciprocal control of their activation and polarization of immune responses. In this review, we describe the role of NK cells and DCs in liver cancer, focusing on the mechanisms involved in their reciprocal control and activation. In this context, intrahepatic NK cells and DCs present unique immunological features, due to the constant exposure to non-self-circulating antigens. These interactions might play a fundamental role in the pathology of primary liver cancer, namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Additionally, the implications of these immune changes are relevant from the perspective of improving the cancer immunotherapy strategies in HCC and ICC patients.
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