The role of AMPK/mTOR/S6K1 signaling axis in mediating the physiological process of exercise-induced insulin sensitization in skeletal muscle of C57BL/6 mice

AbstractThe crosstalk between mTORC1/S6K1 signaling and AMPK is emerging as a powerful and highly regulated way to gauge cellular energy and nutrient content. The aim of the current study was to determine the mechanism by which exercise training reverses lipid-induced insulin resistance and the role of AMPK/mTOR/S6K1 signaling axis in mediating this response in skeletal muscle. Our results showed that high-fat feeding resulted in decreased glucose tolerance, which was associated with decreased Akt expression and increased intramuscular triglyceride deposition in the skeletal muscle of C57BL/6 mice. Impairments in lipid metabolism were accompanied by increased total protein and phosphorylation of S6K1, SREBP-1c cleavage, and decreased AMPK phosphorylation. Exercise training reversed these impairments, resulting in improved serum lipid profiles and glucose tolerance. C2C12 myotubes were exposed to palmitate, resulting in an increased insulin-dependent Akt Ser473 phosphorylation, associated with a significant increase in the level of phosphorylation of S6K1 on T389. All these changes were reversed by activation of AMPK. Consistent with this, inhibition of AMPK by compound C induced an enhanced phosphorylation of both S6K1 and Akt, and silencing of S6K1 with siRNA showed no effect on Akt phosphorylation in both the absence and presence of palmitate cultured myotubes. In addition, compound C led to an elevated SREBP-1c cleavage but was blocked by S6K1 siRNA. In summary, exercise training inhibits SREBP-1c cleavage through AMPK/mTOR/S6K1 signaling, resulting in decreased intramyocellular lipid accumulation. Our results provide new insights into the mechanism by which AMPK/mTOR/S6K1 signaling axis mediates the physiological process of exercise-induced insulin sensitization

Efficacy and safety of combination of ulinastatin and meglumine cyclic adenosine monophosphate in the treatment of acute myocardial infarction, and its effect on serum levels of hs-CRP, cTnI and CK

Purpose: To determine the efficacy and safety of a combination of ulinastatin and meglumine cyclic adenosine monophosphate (cAMP) in the treatment of acute myocardial infarction (AMI), and its effect on serum levels of hypersensitive-c-reactive protein (hs-CRP), cardiac troponin I (cTnI), creatine kinase (CK).Methods: A total of 90 AMI patients admitted to The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar City, Heilongjiang Province, China from January 2019 to January 2020 were selected and randomized (in a 1:1 ration) into control group and study group. Patients in the two groups received meglumine cAMP, while those in the study group were, in addition, treated with ulinastatin. The two groups were compared with regard to clinical efficacy, cardiac function indices, serum biochemical indices, incidence of drug-related side effects, duration and number of episodes of angina pectoris, and levels of neuroendocrine hormones.Results: The study group exhibited remarkably higher treatment effectiveness and cardiac function indices compared to the control group (p < 0.05). However, lower levels of serum biochemical indices, lower total incidence of drug toxicity, smaller number and shorter duration of angina pectoris, and lower levels of panel reactive antibodies (PRA) were observed in the study when compared to control group (p< 0.001).Conclusion: Treatment of AMI patients with the combination of ulinastatin and meglumine cAMP significantly reduces the clinical symptoms of the patients, with remarkable efficacy and high safety. Furthermore, it down-regulates serum levels of hs-CRP, cTnI and CK. Thus, the combination treatment seems superior to the conventional therapy

Coal Ignition Temperature in Oxygen-Enriched CFB Boiler

The oxygen-enriched Circulating fluidized bed (CFB) combustion technology is a new method to reduce CO2 emissions. The coal ignition temperature, Ti F, in an oxygen-enriched CFB boiler is an important parameter for designing the startup burner and for choosing the operating strategy during the startup process. The combustion of five types of coal under four different atmospheres (air, O2 27 %, O2 40%, O2 53%, CO2 as balance gas) was measured in a laboratory scale fluidized bed (FB) with an under-bed preheat system. Using thermocouples and a Gas Analyzer, the changes in bed temperature and the concentration of the different components, such as O2, CO2 and CO, in flue gas were directly measured to determine Ti F. It was found that Ti F decreased with increasing O2 concentration. The differences between the ignition temperatures determined in air and with 27 % O2 were not significant. At lower bed temperatures, for two coal types with higher volatiles, a two stage-ignition for volatiles and char was observed under a high O2 concentration. The time delay between the two stages decreased and finally merged into one with increasing bed temperature. Similar results were obtained in air. The coal with the higher volatile content had a lower ignition temperature in an oxygen-enriched CFB. Comparison of the ignition temperatures obtained by different methods and the feed temperatures in industrial CFB boilers showd that the measured result in a fluidized bed can be used as a reference for oxygen-enriched CFB boilers

Research on Heat Transfer Inside the Furnace of Large Scale CFB Boilers

Field tests in one unit of 135MWe and two units of 300MWe commercial Circulating Fluidized bed (CFB) boilers (A&B) with different structures were carried out. The influence of operating conditions on the thermal boundary layer, local heat transfer coefficient and peripheral distribution of heat transfer coefficient were studied. It was found that, in the 135MWe and 300MWe-A CFB furnace, the thickness of the thermal boundary layer was almost constant, about 100mm, and independent of the height above the distributor and the boiler load. The local heat transfer coefficient increased with increasing load as well as the coal feeding rate and air volume in both the 135MWe and 300MWe-A CFB boilers. The boiler structure and heating surface layout had a great influence on the distribution of the heat transfer coefficient in the large-scale CFB boilers. In both the 135MWe furnace and the 300MWe-B CFB boilers, the heat transfer coefficient was lower in the center than near the corner due to higher suspension density in the corner. In the 300MWe-B CFB with heating surfaces in the furnace, because of the uneven layout of the heating surface and the mal-distribution of gas-solid flow caused by the asymmetric arrangement of cyclones, heat transfer coefficients tended to be higher in the middle part than at the walls

Investigation on The Hydrodynamic Properties in The External Loop of Circulating Fluidized Bed With a Loop Seal

The pressure balance and mass balance are influenced by the characteristics of different components in the loop of a circulating fluidized bed (CFB). Experiments were conducted in a 4.3 m high cold laboratory CFB test rig with a loop seal. With a fixed bed inventory and superficial gas velocity, the pressure drop of the loop seal decreased with increasing aeration, thus causing an increase in the solid circulation flux (Gs). Correspondingly, the pressure drop in the riser became higher with increasing Gs; the pressure drop of the cyclone had a non-linear relationship with Gs, and the transition point was determined in the experiment. Using the laser fiber and gas tracer method, hydrodynamic characteristics in the standpipe were directly measured. It was found that the pressure gradient, voidage, and solid height in the standpipe were affected by the pressure balance in the whole loop. By adjusting the gas flow rate and direction in the standpipe, the gas-solid slip velocity and pressure gradient changed correspondingly. Therefore, the standpipe could maintain the pressure balance and realize self-equilibrium of the loop by absorbing the pressure drop variations of other parts in the system

Investigation of the Lipid-Lowering Effect of Vitamin C Through GSK-3β/β-Catenin Signaling in Zebrafish

Vitamin C (VC) is an essential nutrient for most fish species because of the absence of L-gulonolactone oxidase in the bodies of fish. VC plays a significant role in maintaining the physiological functions and in improving the growth performance, immunity, and survival of fish. In this study, zebrafish (Danio rerio) were treated with 8.2, 509.6, and 1007.5 mg/kg VC diets for 2 weeks, and the muscle samples were collected for gene expression analysis and biochemical index analysis. The results indicated that 509.6 and 1007.5 mg/kg VC diets inhibited glycogen synthase kinase-3β (GSK-3β) expression and induced the expression of β-catenin in the muscle of zebrafish. The mRNA expression of CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS), FAS activity, and the content of glycerol and triglyceride (TG) were decreased in the muscle by 509.6 and 1007.5 mg/kg VC diets. In addition, GSK-3β RNA interference was observed in zebrafish fed with 8.2 and 1007.5 mg/kg VC diets. It was found that GSK-3β RNA interference induced the mRNA expression of β-catenin but decreased the mRNA expression of C/EBPα and FAS, FAS activity, as well as the content of glycerol and TG in the muscle of zebrafish. In ZF4 cells, the mRNA expression of GSK-3β, C/EBPα, and FAS was decreased, but β-catenin expression was increased by 0.1 and 0.5 mmol/L VC treatments in vitro. The glycerol and TG content, and FAS activity in ZF4 cells were decreased by 0.1 and 0.5 mmol/L VC treatments. Moreover, the result of western blot indicated that the protein expression level of GSK-3β was significantly decreased and that of β-catenin was significantly increased in ZF4 cells treated with 0.1 and 0.5 mmol/L VC. The results from in vivo and in vitro studies corroborated that VC exerted the lipid-lowering effect through GSK-3β/β-catenin signaling in zebrafish

Comprehensive analysis of the microbiome and metabolome in pus from pyogenic liver abscess patients with and without diabetes mellitus

IntroductionPyogenic liver abscess (PLA) patients combined with diabetes mellitus (DM) tend to have more severe clinical manifestations than without DM. The mechanism responsible for this phenomenon is not entirely clear. The current study therefore aimed to comprehensively analyze the microbiome composition and metabolome in pus from PLA patients with and without DM, to determine the potential reasons for these differences.MethodsClinical data from 290 PLA patients were collected retrospectively. We analyzed the pus microbiota using 16S rDNA sequencing in 62 PLA patients. In addition, the pus metabolomes of 38 pus samples were characterized by untargeted metabolomics analysis. Correlation analyses of microbiota, metabolites and laboratory findings were performed to identify significant associations.ResultsPLA patients with DM had more severe clinical manifestations than PLA patients without DM. There were 17 discriminating genera between the two groups at the genus level, among which Klebsiella was the most discriminating taxa. The ABC transporters was the most significant differential metabolic pathway predicted by PICRUSt2. Untargeted metabolomics analysis showed that concentrations of various metabolites were significantly different between the two groups and seven metabolites were enriched in the ABC transporters pathway. Phosphoric acid, taurine, and orthophosphate in the ABC transporters pathway were negatively correlated with the relative abundance of Klebsiella and the blood glucose level.DiscussionThe results showed that the relative abundance of Klebsiella in the pus cavity of PLA patients with DM was higher than those without DM, accompanied by changes of various metabolites and metabolic pathways, which may be associated with more severe clinical manifestations

Dynamic reliability sensitivity analysis for inter-story isolation structure under stochastic excitations

Considering the uncertainties of seismic excitation and stochastic parameters of the Inter-story Isolation Structure, the implicit structural response function is transformed into an explicit one by the Stochastic Response Surface Method (SRSM), combined with a probabilistic collocation method based on the linear independence principle. By using the reliability analysis method based on the first-passage failure, the reliability of isolation structure is analyzed and the sensitivity of the reliability of each sub-structure is further analyzed. The results show that conducting sensitivity research based on reliability analysis can provide an important theoretical basis for an optimized and robust design of a random vibration system. The changes of the stiffness and damping ratio of the Isolation Layer have a great influence on the reliability of the system and have different effects on the reliability of different parts of the system. The analysis results of reliability sensitivity could provide system reliability indexes to rank stochastic parameters by their importance, thus improving the efficiency of the structure reliability analysis and optimization design