Research on character of screw pile group composite foundation used in high-speed railway

As a result of rapid development of a high-speed railway and infrastructure in China in recent years, the subgrade deformation and settlement control standards put forward more stringent requirements. Based on ABAQUS 6.14, established finite element model of screw pile group composite foundation. Then obtained the settlement, axial force distribution and pile side resistance distribution of center pile of pile group. Next design parameters sensitive analysis was made, such as pile length, pile spacing and so on, in order to obtain a reasonable design pile parameters by analysis of mechanical behavior

Memetic Differential Evolution with an Improved Contraction Criterion

Memetic algorithms with an appropriate trade-off between the exploration and exploitation can obtain very good results in continuous optimization. In this paper, we present an improved memetic differential evolution algorithm for solving global optimization problems. The proposed approach, called memetic DE (MDE), hybridizes differential evolution (DE) with a local search (LS) operator and periodic reinitialization to balance the exploration and exploitation. A new contraction criterion, which is based on the improved maximum distance in objective space, is proposed to decide when the local search starts. The proposed algorithm is compared with six well-known evolutionary algorithms on twenty-one benchmark functions, and the experimental results are analyzed with two kinds of nonparametric statistical tests. Moreover, sensitivity analyses for parameters in MDE are also made. Experimental results have demonstrated the competitive performance of the proposed method with respect to the six compared algorithms

Individual phosphorylation sites at the C-terminus of the apelin receptor play different roles in signal transduction

The apelin and Elabela proteins constitute a spatiotemporal double-ligand system that controls apelin receptor (APJ) signal transduction. Phosphorylation of multiple sites within the C-terminus of APJ is essential for the recruitment of β-arrestins. We sought to determine the precise mechanisms by which apelin and Elabela promote APJ phosphorylation, and to elucidate the influence of β-arrestin phosphorylation on G-protein-coupled receptor (GPCR)/β-arrestin-dependent signaling. We used techniques including mass spectrometry (MS), mutation analysis, and bioluminescence resonance energy transfer (BRET) to evaluate the role of phosphorylation sites in APJ-mediated G-protein-dependent and β-dependent signaling. Phosphorylation of APJ occurred at five serine residues in the C-terminal region (Ser335, Ser339, Ser345, Ser348 and Ser369). We also identified two phosphorylation sites in β-arrestin1 and three in β-arrestin2, including three previously identified residues (Ser412, Ser361, and Thr383) and two new sites, Tyr47 in β-arrestin1 and Tyr48 in β-arrestin2. APJ mutations did not affect the phosphorylation of β-arrestins, but it affects the β-arrestin signaling pathway, specifically Ser335 and Ser339. Mutation of Ser335 decreased the ability of the receptor to interact with β-arrestin1/2 and AP2, indicating that APJ affects the β-arrestin signaling pathway by stimulating Elabela. Mutation of Ser339 abolished the capability of the receptor to interact with GRK2 and β-arrestin1/2 upon stimulation with apelin-36, and disrupted receptor internalization and β-arrestin-dependent ERK1/2 activation. Five peptides act on distinct phosphorylation sites at the APJ C-terminus, differentially regulating APJ signal transduction and causing different biological effects. These findings may facilitate screening for drugs to treat cardiovascular and metabolic diseases

Identification of potential inhibitors of omicron variant of SARS-Cov-2 RBD based virtual screening, MD simulation, and DFT

Emergence of the SARS-CoV-2 Omicron variant of concern (VOC; B.1.1.529) resulted in a new peak of the COVID-19 pandemic, which called for development of effective therapeutics against the Omicron VOC. The receptor binding domain (RBD) of the spike protein, which is responsible for recognition and binding of the human ACE2 receptor protein, is a potential drug target. Mutations in receptor binding domain of the S-protein have been postulated to enhance the binding strength of the Omicron VOC to host proteins. In this study, bioinformatic analyses were performed to screen for potential therapeutic compounds targeting the omicron VOC. A total of 92,699 compounds were screened from different libraries based on receptor binding domain of the S-protein via docking and binding free energy analysis, yielding the top 5 best hits. Dynamic simulation trajectory analysis and binding free energy decomposition were used to determine the inhibitory mechanism of candidate molecules by focusing on their interactions with recognized residues on receptor binding domain. The ADMET prediction and DFT calculations were conducted to determine the pharmacokinetic parameters and precise chemical properties of the identified molecules. The molecular properties of the identified molecules and their ability to interfere with recognition of the human ACE2 receptors by receptor binding domain suggest that they are potential therapeutic agents for SARS-CoV-2 Omicron VOC

Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo

G protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of depression. Increasing evidence supports the importance of serotonergic and orexin-producing neurons in numerous physiological processes, possibly via a crucial interaction between 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 1 (OX1R). However, little is known about the function of 5-HT1AR/OX1R heterodimers. It is unclear how the transmembrane domains (TMs) of the dimer affect its function and whether its modulation mediates antidepressant-like effects. Here, we examined the mechanism of 5-HT1AR/OX1R dimerization and downstream G protein-dependent signaling. We found that 5-HT1AR and OX1R form constitutive heterodimers that induce novel G protein-dependent signaling, and that this heterodimerization does not affect recruitment of β-arrestins to the complex. In addition, we found that the structural interface of the active 5-HT1AR/OX1R dimer transforms from TM4/TM5 in the basal state to TM6 in the active conformation. We also used mutation analyses to identify key residues at the interface (5-HT1AR R1514.40, 5-HT1AR Y1985.41, and OX1R L2305.54). Injection of chronic unpredictable mild stress (CUMS) rats with TM4/TM5 peptides improved their depression-like emotional status and decreased the number of endogenous 5-HT1AR/OX1R heterodimers in the rat brain. These antidepressant effects may be mediated by upregulation of BDNF levels and enhanced phosphorylation and activation of CREB in the hippocampus and medial prefrontal cortex. This study provides evidence that 5-HT1AR/OX1R heterodimers are involved in the pathological process of depression. Peptides including TMs of the 5-HT1AR/OX1R heterodimer interface are candidates for the development of compounds with fast-acting antidepressant-like effects

Enhanced Hybrid Differential Evolution for Earth-Moon Low-Energy Transfer Trajectory Optimization

It is known that the optimization of the Earth-Moon low-energy transfer trajectory is extremely sensitive with the initial condition chosen to search. In order to find the proper initial parameter values of Earth-Moon low-energy transfer trajectory faster and obtain more accurate solutions with high stability, in this paper, an efficient hybridized differential evolution (DE) algorithm with a mix reinitialization strategy (DEMR) is presented. The mix reinitialization strategy is implemented based on a set of archived superior solutions to ensure both the search efficiency and the reliability for the optimization problem. And by using DE as the global optimizer, DEMR can optimize the Earth-Moon low-energy transfer trajectory without knowing an exact initial condition. To further validate the performance of DEMR, experiments on benchmark functions have also been done. Compared with peer algorithms on both the Earth-Moon low-energy transfer problem and benchmark functions, DEMR can obtain relatively better results in terms of the quality of the final solutions, robustness, and convergence speed

Establishing the Improved Dynamic Model for the Extracorporeal Ultrasonic Lithotripsy Medical Cooperative Robot

The calculus is one of the common diseases with high incidence. The effective treatment method is extracorporeal ultrasonic lithotripsy. At present, it is low about the intelligent and automatic level of the lithotripter, and it has gradually failed to meet the treatment needs. The extracorporeal ultrasonic lithotripsy medical cooperative robot can solve such problems effectively, and it is equally critical for accurate modeling studies of dynamic models. Based on the previous research and experimental basis, this paper proposes a correction theory to improve the accuracy of the dynamic model for the model error in collaborative robot work. The study first establishes the dynamic model and the solid model of the collaborative robot and then subtracts the value of the dynamic model from the solid model to obtain the modified equation. Finally, the accuracy of the dynamic model is improved by modifying the equation. The experiments show that the kinetic model correction theory is effective and can improve the accuracy of the dynamic model modeling after the correction of the torque equation. The experiments show that the improved dynamic model theory is effective and can improve the modeling accuracy of the dynamic model after the correction of the torque equation. The modified equation has the best correction effect in the 5th degree polynomial and can be used for the extracorporeal ultrasonic lithotripsy medical cooperative robot control

Research Advances of Bioactive Sesquiterpenoids Isolated from Marine-Derived Aspergillus sp.

Marine fungi Aspergillus sp. is an important source of natural active lead compounds with biological and chemical diversity, of which sesquiterpenoids are an extremely important class of bioactive secondary metabolites. In this paper, we review the sources, chemical structures, bioactivity, biosynthesis, and druggability evaluation of sesquiterpenoids discovered from marine fungi Aspergillus sp. since 2008. The Aspergillus species involved include mainly Aspergillus fumigatus, Aspergillus versicolor, Aspergillus flavus, Aspergillus ustus, Aspergillus sydowii, and so on, which originate from sponges, marine sediments, algae, mangroves, and corals. In recent years, 268 sesquiterpenoids were isolated from secondary metabolites of marine Aspergillus sp., 131 of which displayed bioactivities such as antitumor, antimicrobial, anti-inflammatory, and enzyme inhibitory activity. Furthermore, the main types of active sesquiterpenoids are bisabolanes, followed by drimanes, nitrobenzoyl, etc. Therefore, these novel sesquiterpenoids will provide a large number of potential lead compounds for the development of marine drugs