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Background: Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer’s disease. Most recently, GLP-1 analogs have been shown to have a significant neuroprotective role in several neurodegenerative diseases. However, few are known on its potential mechanism. Objective: In this study, we report the effect of exendin-4 (Ex-4), a GLP-1 receptor agonist, on amyloid-β(1-42) peptide oligomer-induced apoptosis in a PC12 neuronal cell model. Methods: MTT, DAPI and Annexin-V/PI assays revealed that the viability of PC12 cells decreased in a dose- and time-dependent manner after exposure to amyloid-β(1-42) oligomers. This apoptotic effect could be attenuated by Ex-4 (100-300 nM) pre-treatment, compared with the PC12 cells treated with amyloid-β(1-42) oligomers alone. Moreover, treatment with amyloid-β(1-42) oligomers (10 μM) resulted in a decrease in active- and pro-caspase-3 expression, as well as in Bcl-2 protein expression; suggesting that amyloid-β(1-42) oligomers impaired neuronal cells via the apoptosis signaling pathway. A further study of this mechanism revealed that amyloid-β oligomers (AβOs) decreased the phosphorylation of Akt and CREB. As expected, pre-treatment with Ex-4 (300 nM) increased the expression of anti-apoptotic protein Bcl-2 and reduced active caspase-3 expression levels. In addition, Ex-4 upregulated the phosphorylation levels of Akt and CREB. Conclusions: These findings indicate that GLP-1 analogue Ex-4 has a neuroprotective effect against AβO-induced PC12 cell apoptosis through reversing the impairment of the neuronal survival signaling pathway. This strongly suggests that Ex-4 is a potential therapeutic option for ameliorating AβO-induced neurotoxicity in the clinical application of Ex-4 for AD treatment, particularly when associated with diabetes.

The structure and binding energy of copper clusters of the size range 70 to 150 were studied by using the embedded-atom method. The stability of the structure of the clusters was studied by calculating the average binding energy per atom, first difference energy and second difference energy of copper cluster. Most of the copper clusters of the size n = 70–150 adopt an icosahedral structure. The results show that the trends are in agreement with theoretic prediction for copper clusters. The most stable structures for copper clusters are found at n = 77, 90, 95, 131, 139.

This paper presents a theoretical model and new idea for designing granular fill oil-tanks foundation. The finite difference method was used to analyze the influence of the oil-tanks radius, the modulus, and thickness of the granular fill on the maximum and differential settlement of a granular fill foundation of oiltanks. Comparison of the modelled results with those of traditional method and observation showed that the new method could be used efficiently in practice.

Because cognitive characteristics and mental characteristics of children are limited, the road traffic safety educational methods should stimulate children's interest and make them focus on the taught content. In order to get the better educational method three different kinds of educational methods are analyzed from effect to short-term memory, long term memory and mental load. Through relative analysis and comparative evaluation, the method of combination of ordinary classroom instruction and playing road traffic safety cartoon is the most effective method from the effect of short-term memory, long-term memory and mental load. Multiple representations approach and multicenter method are better than monotonous educational method for children road traffic safety education.

Highway construction progress risks not only influence the development of an enterprise, but also have a great impact on the national overall strength. This paper attempts to analyze construction progress risks of highway qualitatively and quantitatively from the perspective of theory and practice. The weight of each progress risk index could be obtained by using the analytic hierarchy process and entropy-weighted method, considering the expert’s credibility at the same time. Then the highway construction progress risk of overall highway project is analyzed by the fuzzy comprehensive evaluation theory, which can be used to assess highway construction progress risk objectively. The results show that it could improve the cognitive ability of risk management of highway engineering project construction.

Highway traffic safety management system is an open complex system, there are so many impact factors which influence highway safety, in this paper highway traffic safety management system is studied based on the theory of dissipative structure and catastrophe theory, it indicate that the highway safety management system will be stable or unstable under different disturbances, there are two different situation when the highway safety management system is unstable, one is the highway safety management system gradually die out when entropy production greater than 0, another one is highway safety management system will develop into more advanced system when entropy production less than 0. There exist mutation in those two process, the aim of highway traffic safety management is prevent highway traffic safety management system from dying out by effective management measure before mutation when entropy production greater than 0, and evolve to be a more advanced system through mutation when entropy production less than 0.

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