1Rice-rice rotation is the most important intensive cropping system for food security in China. 2 So far, few studies have examined sustainability of double-rice cropping system using partial 3 substitution of fertilizer N (FN) by green manure (GM). The effects of 100% FN (N 100 ) and 4 different substitution rates of FN by GM (80%, 60%, 40% and 20% FN plus 20%, 40%, 60% 5 and 80% N through GM, and represented respectively by N 80 M 20 , N 60 M 40 , N 40 M 60 and 6 N 20 M 80 ) on the rice productivity and N-supplying capacity of paddy soil were evaluated in 7 double-rice system from 2008 to 2013. Soil organic matter and total N content in the 0-15 cm 8 layer and rice grain yield of early and late rice annually increased in N 80 M 20 and N 60 M 40 plots, 9 but decreased in N 100 , N 40 M 60 and N 20 M 80 plots. Compared with N 100 plots, the NH 4 + -N 10 content and agronomic efficiency of applied N significantly increased in N 80 M 20 and N 60 M 40 11 plots. The grain yield and sustainable yield index of rice crops were improved in N 80 M 20 and 12 N 60 M 40 plots, while declined in N 40 M 60 and N 20 M 80 . Soil NO 3 --N content decreased 13significantly under partial substitutions of GM for FN. It can be concluded that the 14 appropriate substitution of GM for FN (e.g. 20%-40%) is beneficial for improving the 15 productivity and sustainability of paddy field under double-rice cropping system. 16 runoff in double-rice cropping systems, although this point still needs to be further proved. In 1 addition, how the nitrification and denitrification of N and NH 3 volatilization are affected by 2
Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both β-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 μM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.
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