分类: 心理学 >> 心理学其他学科 提交时间: 2024-05-06
摘要: Bipolar disorder is a highly burdensome and refractory mental disorder, affecting individuals, families, and society. The challenge in bipolar disorderis that the treatment targeting the depressive state often carries the risk of inducing manic state, and vice versa, with the frequency of these alternating cycles often indicating the severity of the illness. Therefore, reducing the frequency of states switching in bipolar disorder patients and gradually achieving a stable state are crucial for effective treatment. The purpose of this study is to propose a dynamic process model of bipolar disorderstates switching in order to further understand the treatment, patterns of occurrence and development, and pathophysiological mechanisms of bipolar disorder. Considering the remarkable potential of the salience network in brain switching, we have anchored the model on the functionality of the salience network and analyzed and demonstrated the pathways involved in bipolar disorderstates switching within the framework of “physiological-psychological-neurological”. By focusing on the salience network, this model provides valuable insights into the mechanisms underlying bipolar disorderstates switching.
分类: 物理学 >> 核物理学 提交时间: 2023-07-17
摘要: Based on the covariant density functional theory, by employing the core--quasiparticle coupling (CQC) model, the nuclear level density of odd-$A$ nuclei at the saddle point is achieved. The total level density is calculated via convolution of the intrinsic level density and the collective level density. The intrinsic level densities are obtained in the finite-temperature covariant density functional theory, which takes into account the nuclear deformation and pairing self-consistently. For saddle points on the free energy surface in the $(\beta_2, \gamma)$ plane, the entropy and the associated intrinsic level density are compared with those of the global minima. By introducing a quasiparticle to the two neighboring even--even core nuclei, whose properties are determined by the five-dimensional collective Hamiltonian model, the collective levels of the odd-$A$ nuclei are obtained via the CQC model. The total level densities of the $^{234-240}$U agree well with the available experimental data and Hilaire's result. Furthermore, the ratio of the total level densities at the saddle points to those at the global minima and the ratio of the total level densities to the intrinsic level densities are discussed separately.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 mu M) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 180 (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T-1/2: 2 h vs 4.9 h). (C) 2013 Elsevier Ltd. All rights reserved.