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1.
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.  相似文献   
2.
Alumina ceramic porous structures were shaped by the fused deposition of alumina/polyamide 612 composite granules using an FDM 3D printer with a modified extruder to process granulated powder instead of a filament. The composite granules were prepared via thermally induced phase separation (TIPS). Firstly, in order to determine the proportion of polymer/solvent to be used in the TIPS process, different volume fractions of PA612 in dimethyl sulfoxide (DMSO) were studied (0.01 to 0.20), and the granules obtained were characterized by SEM, DSC, and Raman spectroscopy. Secondly, the addition of different ceramic loadings to the PA612/DMSO solution was studied with the aim of determining the amount to be used for preparing the composite granules by TIPS. In particular, the effect of the alumina content on the morphology and size of the obtained composite granules was studied. In addition, rheological properties (oscillatory and rotational tests) of the feed materials were studied. Finally, the printing conditions, including the nozzle temperature and nozzle diameter, and the extrusion process, were optimized in order to obtain porous structures with good quality. Alumina porous structures were successfully printed, debinded, and sintered. Adequate bonding between layers was achieved, and no defects at interfaces were detected.  相似文献   
3.
Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time.  相似文献   
4.
Thin multilayer coatings of ZrO2–Y2O3–Al2O3 were prepared using the sol-gel method and dip-coating technique in order to advance in the study of what influence the incorporation of Al2O3 has on films of Y2O3-doped ZrO2, investigating its role in the synthesis of the solutions and in the characteristics and properties of the coatings. After the characterization of the solutions used in the process, the microstructure of the films was studied and their mechanical behaviour and resistance to thermal shock were determined so as to optimize the characteristics and functionality of these coatings. With increased alumina content, 3YSZ-Al2O3 (20 mol%), the cubic phase of the zirconia disappeared completely at the sintering temperature used (700 °C), resulting in the tetragonal phase with Al in solution. There was also a decrease in the coatings' hardness and Young's modulus, and an increase in toughness and resistance to thermal shock. These results allow guidelines to be established for the design of multilayer structures that are, tougher, more resistant, and have improved surface properties.  相似文献   
5.
Targeting the innate immune system has attracted attention with the development of anti- CD47 antibodies. Anti-CD47 antibodies block the inhibition of the phagocytic activity of macrophages caused by the up-regulation of CD47 on tumor cells. In this study, public genomic data was used to identify genes highly expressed in breast tumors with elevated CD47 expression and analyzed the association between the presence of tumor immune infiltrates and the expression of the selected genes. We found that 142 genes positively correlated with CD47, of which 83 predicted favorable and 32 detrimental relapse-free survival (RFS). From those associated with favorable RFS, we selected the genes with immunologic biological functions and defined a CD47-immune signature composed of PTPRC, HLA-E, TGFBR2, PTGER4, ETS1, and OPTN. In the basal-like and HER2+ breast cancer subtypes, the expression of the CD47-immune signature predicted favorable outcome, correlated with the presence of tumor immune infiltrates, and with gene expression signatures of T cell activation. Moreover, CD47 up-regulated genes associated with favorable survival correlated with pro-tumoral macrophages. In summary, we described a CD47-immune gene signature composed of 6 genes associated with favorable prognosis, T cell activation, and pro-tumoral macrophages in breast cancer tumors expressing high levels of CD47.  相似文献   
6.
7.
We present a novel comprehensive optimization model for designing reconfigurable machining lines. Due to the proposed fine mathematical modelling, it is possible to optimize simultaneously the whole set of machines and machining modules as well as their cutting parameters, their configuration that will be used for processing of each part and part position at each machine. The experimental results show that the proposed optimization approach substantially outperforms the existing heuristic design method and therefore it can be used by the designers in order to reduce the total system cost and improve the efficiency of reconfigurable machining lines.  相似文献   
8.
Greenhouse gases emitted into the atmosphere by burning of fossil fuels cause global warming. One option is obtaining biodiesel. Nannochloropsis oculata was cultured under different light intensities and reactors at 25°C for 21 days with f/2 medium to assess their effects on cell density, lipid, and fatty acids (FAs). N. oculata improved cell density on fed-batch glass tubular reactor (7 L) at 200 μmol E m−2 s−1, yielding 3.5 × 108 cells ml−1, followed by fed-batch Erlenmeyer flask (1 L) at 650 μmol E m−2 s−1 with 1.7 × 108 cells ml−1. The highest total lipid contents (% g lipid × g dry biomass−1) were 44.4 ± 0.8% for the reactor (1 L) at 650 μmol E m−2 s−1 and 35.2 ± 0.2% for the tubular reactor (7 L) at 200 μmol E m−2 s−1, until twice as high compared with the control culture (Erlenmeyer flask 1 L, 80 μmol E m−2 s−1) with 21.2 ± 1%. Comparing the total lipid content at 200 μmol E m−2 s−1, tubular reactor (7 L) and reactor 1 L achieved 35.2 ± 0.2% and 28.3 ± 1%, respectively, indicating the effect of shape reactor. The FAs were affected by high light intensity, decreasing SFAs to 2.5%, and increased monounsaturated fatty acids + polyunsaturated fatty acids to 2.5%. PUFAs (20:5n-3) and (20:4n-3) were affected by reactor shape, decreasing by half in the tubular reactor. In the best culture, fed-batch tubular reactor (7 L) at 200 μmol E m−2 s−1 contains major FAs (16:0; 38.06 ± 0.16%), (16:1n-7; 30.74 ± 0.58%), and (18:1n-9; 17.15 ± 0.91%).  相似文献   
9.
The isosteric heat of adsorption is an important thermodynamic property used to characterize and optimize adsorption processes. In this work, analytic expressions for isosteric heats of adsorption are derived for a collection of commonly used isotherm models and a two-dimensional molecular equation of state based on the SAFT-VR approach. The use of these expressions is presented with an example of adsorption of nitrous oxide, N2O, on biochar, which is a waste biomass charcoal that exhibits high adsorption potential. The results show that accurate fitting of the adsorption isotherms leads to consistent results obtained with different approaches; however, the predicted isosteric heat of adsorption exhibits strong variations in the regions where experimental data is insufficient such in the region of low pressure/low coverage. Convergence on the prediction of the isosteric heat of adsorption by the different models is only observed in the region where no extrapolation of experimental data is needed.  相似文献   
10.
The histidine phosphocarrier protein (HPr) kinase/phosphorylase (HPrK/P) modulates the phosphorylation state of the HPr protein, and it is involved in the use of carbon sources by Gram-positive bacteria. Its X-ray structure, as concluded from crystals of proteins from several species, is a hexamer; however, there are no studies about its conformational stability, and how its structure is modified by the pH. We have embarked on the conformational characterization of HPrK/P of Bacillus subtilis (bsHPrK/P) in solution by using several spectroscopic (namely, fluorescence and circular dichroism (CD)) and biophysical techniques (namely, small-angle X-ray-scattering (SAXS) and dynamic light-scattering (DLS)). bsHPrK/P was mainly a hexamer in solution at pH 7.0, in the presence of phosphate. The protein had a high conformational stability, with an apparent thermal denaturation midpoint of ~70 °C, at pH 7.0, as monitored by fluorescence and CD. The protein was very pH-sensitive, precipitated between pH 3.5 and 6.5; below pH 3.5, it had a molten-globule-like conformation; and it acquired a native-like structure in a narrow pH range (between pH 7.0 and 8.0). Guanidinium hydrochloride (GdmCl) denaturation occurred through an oligomeric intermediate. On the other hand, urea denaturation occurred as a single transition, in the range of concentrations between 1.8 and 18 µM, as detected by far-UV CD and fluorescence.  相似文献   
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