Chalcones containing tertiary amine side-chains have potent activity as acetylcholinesterase (AChE) inhibitors. However, the effects of the location of the tertiary amine groups as well as of other groups on AChE and butyrylcholinesterase (BChE) activity have not been reported. Here, we report the synthesis and testing of 36 new coumarin-chalcone hybrids (5d-7j, 9d-11f, 12k-13m) against AChE and BChE. The nature and position of the chalcone substituents had major effects on inhibitory activity as well as selectivity for AChE over BChE. Compounds with para-substituted chalcone fragments in which the substituents were choline-like had potent activity against AChE and poor activity against BChE, while ortho-substituted analogs exhibited an opposite effect. Replacement of the terminal amine groups by amide, alkyl or alkenyl groups abrogated activity. Compound 5e showed potent inhibitory activity [Formula: see text]) and good selectivity for AChE over BChE (ratio 27.4), and a kinetic study showed that 5e exhibited mixed-type inhibition against AChE. Computational docking results indicate that 5e binds to Trp 279, Tyr334 and Trp 84 in AChE, but only to Trp 82 in BChE. Overall, the results show that coumarin-chalcone hybrids with choline-like side-chains have promising activity and selectivity against AChE and be promising therapeutic leads for Alzheimer's disease.

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Through the current situation survey of geological environmental disasters caused by limestone mining in Chongqing and combined with the principles of establishing evaluation index system and industry experts’ advices, we get the geological environmental impact assessment system of open-pit limestone mining which is consist of 7 dimensions and 25 indexes. Using analytic hierarchy process (AHP) to assign the weight of 25 indexes and based on membership functions of trapezoidal distribution to establish evaluation standard, the fuzzy comprehensive evaluation model is constructed. According to the principle of maximum membership degree, we get the influence degree of the geological environmental system affected by the open-pit limestone mining in Chongqing. This model makes the impact on geological environment of limestone mining quantitative and plays a certain guiding role in the local environmental protection strategy formulation and geological disaster prevention.

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In order to improve the machining efficiency of the duralumin turbine rotor of maglev molecular pump, this paper proposes a new double-spindle horizontal milling machining center structure. Through a brief introduction to other types of machine tools, describes the characteristics of this new machine tool and symmetrical machining implementation. This paper proposes a new double-spindle horizontal milling machining centers so that the machining efficiency of duralumin turbine rotors is improve 100% more than that of the traditional machine tool in theory. Moreover, its machining accuracy get relative improve as the decrease of the dividing accumulative error. At the same time, the cost of workpiece is reduced greatly.