Glycogen synthase kinase-3 (GSK-3) is a kind of serine-threonine protein kinase. It places important roles in several signaling pathways and it is a key therapeutic target for a number of diseases, such as diabetes, cancer, Alzheimer's disease and chronic inflammation. Mg(2+) ions which interact with ATP are conserved in GSK. They are important in phosphoryl transfer. Li(+) is an inhibitor for GSK-3. It is used to treat bipolar mood disorder. This paper illustrates the effect of Li(+) on GSK-3. When Mg(I)(2+) is replaced by Li(+), the atom fluctuation of GSK-3 will rise, and the in-line phosphoryl transfer mechanism is probably demolished and the binding of pre-phosphorylated substrates may be disturbed. All the results we obtained clearly suggest that inhibition to GSK-3 is caused by the Mg(I)(2+) replacement with Li(+).

No abstract

The settling of cohesive sediment is ubiquitous in aquatic environments, and the study of the settling process is important for both engineering and environmental reasons. In the settling process, the silt particles show behaviors that are different from non-cohesive particles due to the influence of inter-particle cohesive force. For instance, the flocs formed in the settling process of cohesive silt can loosen the packing, and thus the structural densities of cohesive silt beds are much smaller than that of non-cohesive sand beds. While it is a consensus that cohesive behaviors depend on the characteristics of sediment particles (e.g., Bond number, particle size distribution), little is known about the exact influence of these characteristics on the cohesive behaviors. In addition, since the cohesive behaviors of the silt are caused by the inter-particle cohesive forces, the motions of and the contacts among silt particles should be resolved to study these cohesive behaviors in the settling process. However, studies of the cohesive behaviors of silt particles in the settling process based on particle-resolving approach are still lacking. In the present work, three-dimensional settling process is investigated numerically by using CFD-DEM (Computational Fluid Dynamics-Discrete Element Method). The inter-particle collision force, the van der Waals force, and the fluid-particle interaction forces are considered. The numerical model is used to simulate the hindered settling process of silt based on the experimental setup in the literature. The results obtained in the simulations, including the structural densities of the beds, the characteristic lines, and the particle terminal velocity, are in good agreement with the experimental observations in the literature. To the authors' knowledge, this is the first time that the influences of non-dimensional Bond number and particle polydispersity on the structural densities of silt beds have been investigated separately. The results demonstrate that the cohesive behavior of silt in the settling process is attributed to both the cohesion among silt particles themselves and the particle polydispersity. To guide to the macro-scale modeling of cohesive silt sedimentation, the collision frequency functions obtained in the numerical simulations are also presented based on the micromechanics of particles. The results obtained by using CFD-DEM indicate that the binary collision theory over-estimated the particle collision frequency in the flocculation process at high solid volume fraction.