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71.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.  相似文献   
72.
Microwaves at 2.45 GHz have been applied to ignite the combustion synthesis of compacted Ti–Si–C powders mixtures, having 1:1:1 atomic ratio, in order to join SiC-based components. A mixture of different refractory phases such as TiC and TiSi2 were obtained. Depending on the synthesis conditions, no residual silicon in the joint was detected, suggesting the suitability of the here proposed experimental joining approach for nuclear plants and high temperature applications. A simplified model was developed with the aim of obtaining a deeper understanding of the here proposed rapid, almost pressure-less and localized heating joining method. Experimental and numerical simulation results demonstrate that joining of SiC can be rapidly obtained with minimization of heat affected zones in the SiC substrates. Maximum apparent shear strength values of the joints ranged from 9.9 to 45.1 MPa, depending on the process conditions.  相似文献   
73.
In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62.9 ± 5.9% vs. 33.3 ± 5.7% maximal oxidation), as measured by the intracellular redox sensor roGFP. Cyclic stretch also increased sGCβ protein expression (2.5 ± 0.9-fold), sGC activity (1.5 ± 0.2-fold) and cGMP levels (1.8 ± 0.2-fold), as well as iNOS mRNA and protein expression (3.0 ± 0.9 and 2.6 ± 0.7-fold, respectively) relative to control cells. An antioxidant, recombinant human superoxide dismutase (rhSOD), significantly decreased stretch-induced cytosolic oxidative stress, but did not block stretch-induced sGC activity. Inhibition of iNOS with 1400 W or an iNOS-specific siRNA inhibited stretch-induced sGC activity by 30% and 68% respectively vs. static controls. In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in PASMC from fetal lambs. The mechanism that produces iNOS and sGC upregulation is not yet known, but we speculate these effects represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress. A better understanding of the interplay between these two distinct pathways could provide key insights into future avenues to treat infants with pulmonary hypertension.  相似文献   
74.
Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells.  相似文献   
75.
Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the contribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents.  相似文献   
76.
Gelatin reactivity with isocyanate was studied by using the easy detectable 1-naphthyl-isocyanate (NphI). Four different NphI/gelatin feed ratios were investigated with NphI molar amount ranging between 1/10 and 1/1 with respect to the possible reactive groups of gelatin. The reactions were carried out at 45 °C in DMSO as solvent, under nitrogen atmosphere. Modified gelatin samples were characterized by IR, UV–VIS, fluorescence spectroscopies as well as by proton and DOSY NMR. Spectroscopy results allow to evidence the presence of both bonded and unbonded naphthyl derivatives in the gelatin samples. Unbonded species were present particularly at the highest NphI/gelatin feed ratio and their formation was correlated to the increasing competition of the reaction with water since the amount of available reactive groups on gelatin was comparable or smaller than the amount of residuum water in dry gelatin.  相似文献   
77.
Si/Al MCM-41 type mesoporous compounds, as such or containing small amounts of metal (Ni, Rh or Pt), were investigated in the synthesis of clean diesel fuels by oligomerisation of orphan olefin streams. Very good catalytic performances were obtained with C4 and C5 olefins, while almost no conversion occurred with ethylene. The activity increased with increasing reaction pressure, temperature and contact time, while high Si/Al ratios had a negative effect on both activity and catalyst stability. The presence of small amount of metal inside the mesoporous structure did not significantly modify the catalytic activity, although specific effects were detected for each element. Since the evaluation of the cetane number by H-NMR gave rise to values about 20% lower than the actual value, a new and more complex algorithm is proposed to calculate the cetane number. Using the proposed algorithm, a good correlation index was found between calculated and motor values for pure compounds. Further study is necessary to move from pure compounds to experimental mixtures.  相似文献   
78.
Hybrid materials obtained through a Microwave-assisted grafting of organic functional groups on mesoporous silica (MCM-41 type) have been characterized by X-ray powder diffraction, TG-DSC, N2 adsorption, solid state 13C- and 29Si-NMR, TEM and SEM. The studied grafting procedure is effective in the preparation of hybrid organosilicas under solvent-free conditions. Microwaves allows an ultra-fast and clean functionalization of the mesoporous materials and the method has been applied to produce a wide series of functional materials. The hybrid materials maintain the original mesoporous structure when the loading of linked organic groups does not exceed 10 %. In this cases, the slight pore volume reduction is linearly correlated to the organic amount in the product. If functional groups able to interact among them through hydrogen bond are used, hybrid materials exhibit high Organic/SiO2 ratios and low pore volumes due to the formation of a network occluding the pores, where functional groups of free organosilane molecules interacts with the functional groups of molecules linked to the matrix. NMR data confirm that the network is composed by organosilane molecules linked or not to the framework. Acid washing is able to labilize hydrogen bond and open the network. In the case of bulky but chemically inert functionalising agents the network is not produced.  相似文献   
79.
Psychophysical experiments were conducted in the UK, Taiwan, France, Germany, Spain, Sweden, Argentina, and Iran to assess colour emotion for two‐colour combinations using semantic scales warm/cool, heavy/light, active/passive, and like/dislike. A total of 223 observers participated, each presented with 190 colour pairs as the stimuli, shown individually on a cathode ray tube display. The results show consistent responses across cultures only for warm/cool, heavy/light, and active/passive. The like/dislike scale, however, showed some differences between the observer groups, in particular between the Argentinian responses and those obtained from the other observers. Factor analysis reveals that the Argentinian observers preferred passive colour pairs to active ones more than the other observers. In addition to the cultural difference in like/dislike, the experimental results show some effects of gender, professional background (design vs. nondesign), and age. Female observers were found to prefer colour pairs with high‐lightness or low‐chroma values more than their male counterparts. Observers with a design background liked low‐chroma colour pairs or those containing colours of similar hue more than nondesign observers. Older observers liked colour pairs with high‐lightness or high‐chroma values more than young observers did. Based on the findings, a two‐level theory of colour emotion is proposed, in which warm/cool, heavy/light, and active/passive are identified as the reactive‐level responses and like/dislike the reflective‐level response. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2012  相似文献   
80.
Rice husk, an agricultural waste, is abundantly available in many countries such as China, India, Brazil, US, and South East Asia. Despite the massive production of rice husk, it is mainly disposed to landfill. In this work, utilization of rice husk for a potential waste-water treatment is evaluated, along with subsequent encapsulation of the adsorbed heavy metals (Pb and Cd) inside a porous glass-ceramic. Vitrified bottom ash (another source of waste) was mixed with foaming agents in dif- ferent weight ratios (40:60, 50:50, and 60:40) to prepare a glass matrix for encapsulation of Pb-/Cd-loaded rice husk. It was shown that using 40 wt% vitrified bottom ash with 60 wt% foaming agents leads to a foam glass with the best pore size distribution. Therefore, this batch was further mixed with 70 volume% (5 wt%) heavy metal-loaded rice husk and was heat-treated at 750°C for 3 hours. The final glass-ceramic porous structure was char acterized using SEM, XRD, compression test, and it was shown that it is safe to be used as it passes the EN12457-2 leaching test.  相似文献   
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