Study on the mechanism of cholic acid derivatives in traditional Chinese medicine based on the regulation of gene expression

Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.

Lead-free bilayer heterometallic halide perovskite with reversible phase transition and photoluminescence properties

The layered heterometallic halide perovskites, as a newly explored material, have attracted great scientific attention. As one of the representatives of perovskite, lead-free or lead-substituted perovskite materials are widely applied in photovoltaic, sensors, catalysis, detectors and other fields. Therefore, it is urgent to carry out more systematic exploration and expand applicable preresearch, so as to make more interesting discoveries in this new hot spot. As an interesting candidate, heterometallic compounds will introduce more structural adjustability and novel physical properties, which is the main feature to be selected as the research hotspot. Here, we reported a lead-free bilayer heterometallic Ruddlesden-Popper(RP) type perovskite, [(MACH)_(2)CsAgBiBr_(7)](MACH = cyclohexanemethylamine), which possesses a reversible phase transition at 379.6 K/375.1 K during heating-cooling cycle. Besides, it exhibits reddish-brown light emission under 365 nm, meanwhile, CIE chromaticity coordinate is(0.32, 0.45) on the yellow side and correlated color temperature is about 6000 K. Moreover, both the experimental data and theoretical calculation results suggest that [(MACH)_(2)CsAgBiBr_(7)] shows indirect semiconducting characteristics. In summary, this work will inspire the design of lead-free heterometallic perovskite materials for the application of sensors and light-emitting diodes(LEDs) fields.

Damage assessment and diagnosis of hydraulic concrete structures using optimization-based machine learning technology

Concrete is widely used in various large construction projects owing to its high durability,compressive strength,and plasticity.However,the tensile strength of concrete is low,and concrete cracks easily.Changes in the concrete structure will result in changes in parameters such as the frequency mode and curvature mode,which allows one to effectively locate and evaluate structural damages.In this study,the characteristics of the curvature modes in concrete structures are analyzed and a method to obtain the curvature modes based on the strain and displacement modes is proposed.Subsequently,various indices for the damage diagnosis of concrete structures based on the curvature mode are introduced.A damage assessment method for concrete structures is established using an artificial bee colony backpropagation neural network algorithm.The proposed damage assessment method for dam concrete structures comprises various modal parameters,such as curvature and frequency.The feasibility and accuracy of the model are evaluated based on a case study of a concrete gravity dam.The results show that the damage assessment model can accurately evaluate the damage degree of concrete structures with a maximum error of less than 2%,which is within the required accuracy range of damage identification and assessment for most concrete structures.

Juvenile hormone membrane signaling phosphorylates USP and thus potentiates 20-hydroxyecdysone action in Drosophila

Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.