Search

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe–/– mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

The heart is a high energy demand organ and enhancing mitochondrial function is proposed as the next-generation therapeutics for heart failure. Our previous study found that anthelmintic drug niclosamide enhanced mitochondrial respiration and increased adenosine triphosphate (ATP) production in cardiomyocytes, therefore, this study aimed to determine the effect of niclosamide on heart failure in mice and the potential molecular mechanisms. The heart failure model was induced by transverse aortic constriction (TAC) in mice. Oral administration of niclosamide improved TAC-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction in mice. Oral administration of niclosamide reduced TAC-induced increase of serum IL-6 in heart failure mice. In vitro, niclosamide within 0.1 μM increased mitochondrial respiration and ATP production in mice heart tissues. At the concentrations more than 0.1 μM, niclosamide reduced the increased interleukin- 6 (IL-6) mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 derived macrophages. In cultured primary cardiomyocytes and cardiac fibroblasts, niclosamide (more than 0.1 μM) suppressed IL-6- and phenylephrine-induced cardiomyocyte hypertrophy, and inhibited collagen secretion from cardiac fibroblasts. In conclusion, niclosamide attenuates heart failure in mice and the underlying mechanisms include enhancing mitochondrial respiration of cardiomyocytes, inhibiting collagen secretion from cardiac fibroblasts, and reducing the elevated serum inflammatory mediator IL-6. The present study suggests that niclosamide might be therapeutic for heart failure.

A harmonious relationship between police and people is an important part of the harmonious society construction. It is significant to the promotion of public security work and the harmonious society construction that we understand, handle and evaluate the harmonious relationship between police and people. We analyze the basic connotation and research meaning of harmonious relationship between police and people, generalize six main principles of constructing the evaluation index system of harmony degree of relationship between police and people, construct the evaluation index system of harmony degree of relationship between police and people based on hierarchical model .Then we will establish the mathematical model of evaluation index system of harmony degree of relationship between police and people further, realize the quantitative evaluation of harmony degree, find the disharmonious factors which influence the harmonious relationship between police and people. This makes the public security organs constantly adjust the working thought and working measures, so as to ensure the correctness of the working direction and promote the construction of a harmonious relationship between police and people.

To evaluate the correlation between osteoporotic vertebral compression fractures and spinal sagittal imbalance, in order to provide a reference for clinical treatment.From September 2013 to March 2015, 60 elderly patients with old osteoporotic vertebral compression factures (observation group) and 60 healthy elderly people (control group) were studied. Whole-spine anteroposterior and lateral view X‑ray photographs were taken from all participants, the number and location of fractured vertebrae were recorded, and sagittal parameters in both groups were compared. The observation group was divided into three subgroups according to the number of fractured vertebrae. The C7/sacrofemoral distance (SFD) ratio in the three subgroups was compared, and the correlation between the number of fractured vertebrae and the C7/SFD ratio was analyzed.The thoracic kyphotic angle in patients in the observation group was higher than in the control group (P 0.05), the lumbar lordotic angle in patients in the observation group was lower than in the control group (P 0.05), the absolute value of the T1 spinopelvic inclination angle in patients in the observation group was lower than in the control group (P 0.05), and the C7/SFD ratio of patients in the observation group was higher than in the control group (P 0.05). C7/SFD ratios of the subgroups differed from each other, and the number of fractured vertebrae and C7/SFD ratio were positively correlated.Osteoporotic vertebral compression fractures can change local spinal sagittal alignment, multiple vertebral compression fractures can cause spinal sagittal imbalance, and the number of fractured vertebrae and the degree of forward movement of the spine were positively correlated.

For the tunnel with high ground stress and soft surrounding rock, the deformation instability is the high frequency and great harm geological hazard. The supporting measure has become a important technique problem. This paper based on the Wuduxi tunnel, the characteristics of deformation and instability mechanism of surrounding rock and supporting structure are analyzed by means of the engineering geological investigation, theoretical analysis and field monitoring. The supporting measure include that using the steel floral tube to back up sidewall, adding support arch and filling foamed concrete, grouting reinforcement in basement. Finally, we use the field monitoring to check the supporting effect. The result shows that the supporting measure could achieve the desired treat effect and it has reference meaning to similar engineering.

To research the mechanical regularity of steel frame in tunnel, Steel frame and Sprayed concrete Combination Model is applied and the large-section loess tunnel of highway is taken as an example. The hoop stress of flange and the radial stress of web were analyzed, the research results show that:The most areas of hoop stress of flange is in press, the compress value which most areas of flank edge is larger than the outer flank flange in the same area of steel frame. The hoop and radial stress of web is in press. The hoop stress value which most areas of flank edge are larger than the radial stress in the same area of steel frame.

In order to solve the problem of multi-index amalgamation on the reliability evaluation for tunnel lining with cracks, this paper based on extension theory, use matter element model theory to establish the matter element of the reliability evaluation for tunnel lining with cracks, use the dependent function to establish the relevance between matter element and reliability grade, combine the research result of the Beiru tunnel lining cracks disease to evaluate the reliability. The results show that it could consider the multi-index of the cracks to use the extension theory to evaluate the reliability of the tunnel lining with cracks, and the evaluation results are more scientific and reasonable. It is viable to use the dimensionless parameters to represent the crack geometry. In the K6, the treatment scheme is mechanical reinforcement. In the K2 and K3,the treatment scheme is surface sealing. The reliability evaluation results supply theory basis and technical guidance for the tunnel long-term health service and the disease treatment.

To research the mechanics characteristic of support structure of shallow-buried large section loess tunnel with different construction methods, 3D Numerical Simulation is applied and the large-section loess tunnel of highway is taken as an example. Comparing mechanics characteristic of support structure in three types of construction method conditions, the research results show that:The Benching stepping method which caused large surrounding rock deformation can reduce the value of structural performance. While the Both side heading is just opposite.

In order to analysis the internal relation between the matric suction change and the tunnel disease, the paper combines the Dayoushan tunnel as an engineering example, uses the mathematical, field monitoring and model shear test and to analysis the the change rule of the martic suction and the influence of martic suction on the tunnle supporting force and plastic zone. The results show that when the water content is increasing, the unsaturated loess matric suction is reduction, the force of tunnel support is increasing and the radius of plastic zone is increasing. Due to the influence of surface water infiltration, the matric suction of the around soil in Dayoushan tunnel is reduction and cause the crown settlement, landslides and lining cracks. The disease treatment mainly lies in keeping the drainage system is smooth and secure for waterproof. For the similar unsaturated loess tunnel, the research results have reference significance.

For a comprehensive analysis of the mechanical properties of compound-umbrella arch in the unsymmetrically loaded tunnel entrance, we focus on the force characteristics to optimize the structure of composite umbrella arch, and improve its economic efficiency. The stresses on the bottom of pile, the pile and the steel arch were monitored, and analyzed by the finite element software. The results show that, on the bias terrain, the stress of the pile bottom is nonuniform with uneven settlement. The stress distribution is very complex, where the tensile stress appears on the pile bottom, the compressive stress takes place on the arch foot and the vault, which is not good to the stability of the overall umbrella arch. As both sides of the umbrella arch bear a large different force, the piles on both sides of the umbrella arch subject to large bending moment and axial force, which improve the stability of the tunnel entrance.

Combine the specific bridge, an analytical on the bridges static performance studied through the finite element model analysis and field test method. Summary and analyze the displacement and stress variation law of the main truss, longitudinal beams and beams which the bolt and weld superstructure steel truss bridges are effected by static loads, and compared field test results with theory value. Application practice proves that the evaluation standard and inspection of steel truss bridge is appropriate.

The 3D finite element simulation was adopted to study the globality stability of tunnel caused by the different excavation length of invert. Kelan-Linxian highway loess tunnels were taken as an example. The research results are shown as follows: The vertical displacement and horizontal convergence increased by the increasing of the excavation length of the invert. But the latter increase range is larger than the former. The horizontal convergence in sidewall is convergence value is greater than the level of the arch and the corner, the horizontal displacement primarily occurred in the side wall position. The surrounding rocks maximum plastic strain occurred in side wall and corner wall in 4 working conditions. The plastic zone occurred around from arch corner to wall side. In Tab. 4, the maximum plastic strain is increased by the excavation length of inverts increasing.

Based on the Pasternak elastic foundation beam theory, mechanical models solving process of pipe-roof based on the MATLAB is elaborate, and the mechanical behavior of pipe-roof reinforcement is analyzed. Results show that the pipe-roof can play an leveraged part in surrounding rock, which can make the deformation and the load around tunnel face effectively passing to no excavation section near the excavation. In pipe-roof support conditions, the longitudinal influence scope of tunnel due to excavation is about 1.3~1.5 times the excavation height.

Through theoretical calculation, systemic analysis of dynamic performance of the 64m single and double line railway steel truss bridges on the different speed of train loads. Contrast and analysis the main dynamic performance parameters of bridges on the differend speed. In 64m steel truss bridges in Heavy-Haul Coal Line application practice proves that the deflection of the bridge to the speed is insensitive. The vertical acceleration and horizontal acceleration is sensitive to speed. The speed 80km/h is the speed which lead to the maximum vertical acceleration of the single line and double line in light-load condition.

Surrounding rock stress is a one of significant feedback information after tunnel excavation. It is also an important factor influencing the stability of the tunnel, and the premise to determine accurately the tunnel stability. For tunnel surrounding rocks stress determined by many uncertain factors, it is difficult to accurately predict. The BP neural network model for predicting on the stress of the tunnel surrounding rock stress is created. Comparative analyze the results of the surrounding rocks stress prediction on expressway tunnel by momentum gradient algorithm, L-M algorithm and bayesian regularization algorithm. Results show that the use of bayesian regularization algorithm for neural network model has higher forecast accuracy. It can be applied in engineering practice.

Through theoretical calculation, systemic analysis of dynamic performance of the 64m single and double line railway steel truss bridges on the expanding condition and conventional condition. Contrast and analysis the main dynamic performance parameters of bridges on the two kinds of operating condition. In 64m steel truss bridges of Shuozhou-Huanghuagang Railway application practice proves that on expanding heavy-load condition, the main dynamic performance parameters of bridges are slightly larger than conventional condition, but the variation law of vertical acceleration of mid-span is different.

The bulk tiles of ceramic fibers reinforced aerogel were prepared from two reinforcements, evenly dispersed ceramic fibers and sintered tiles. It has been found that ceramic fiber-reinforced aerogels showed higher thermal conductivity than aerogel itself. Shrinkage of aerogels in chopped fiber reinforced aerogel composites showed similar tendency as pure aerogel during gelation, but the shrinkage was prohibited during supercritical drying. By contrary, in the case of sintered tile reinforced aerogel, shrinkage of aerogel was completely limited in both gelation and drying processes. Average of about 50% increase of compressive strengths of the sintered tile reinforced aerogel to sintered tiles were obtained with an average density increase of about 36%, their thermal conductivity depressed slightly.

Chlorzoxazone has been reported to activate the intermediate-conductance, Ca(2+)-activated K(+) channels in aortic endothelial cells and to relax the artery. The aim of the present study was to characterize the chlorzoxazone-induced relaxation of rat thoracic artery. Chlorzoxazone did not affect the tension of the thoracic artery rings at rest, but relaxed the precontraction induced by 1 muM noradrenaline in an endothelium independent manner. Preincubation with chlorzoxazone also antagonized the contraction induced by 1 microM noradrenaline or 25 mM KCl. The chlorzoxazone-induced relaxation of the thoracic artery pre-contracted by noradrenaline was suppressed by 5 mM tetraethylammonium, 75 mM ethanol and 2 microM paxilline, but not by 2 microM clotrimazole. Chlorzoxazone relaxed the 4-aminopyridine-induced contraction. The pattern of chlorzoxazone-induced relaxation was different from that of verapamil, the L-type Ca(2+) channel blocker. The inhibition of the noradrenaline-induced contraction by chlorzoxazone was attenuated when chlorzoxazone treatment was prolonged to 4 h. No difference in the contraction-relaxation was found between the artery rings from normal rats and those from rats that received 100 mg/kg chlorzoxazone for 7 days. We conclude that chlorzoxazone abolishes the contraction of rat thoracic artery induced by noradrenaline and that the effect of chlorzoxazone is endothelium independent and also not mediated by intermediate-conductance, Ca(2+)-activated K(+) channels.