Quantitative proteomics reveals the protective effects of Yinchenzhufu decoction against cholestatic liver fibrosis in mice by inhibiting the PDGFRß/PI3K/AKT pathway.

Introduction: Yinchenzhufu decoction (YCZFD) is a traditional Chinese medicine formula with hepatoprotective effects. In this study, the protective effects of YCZFD against cholestatic liver fibrosis (CLF) and its underlying mechanisms were evaluated. Methods: A 3, 5-diethoxycarbonyl-1, 4-dihydro-collidine (DDC)-induced cholestatic mouse model was used to investigate the amelioration of YCZFD on CLF. Data-independent acquisition-based mass spectrometry was performed to investigate proteomic changes in the livers of mice in three groups: control, model, and model treated with high-dose YCZFD. The effects of YCZFD on the expression of key proteins were confirmed in mice and cell models. Results: YCZFD significantly decreased the levels of serum biochemical, liver injury, and fibrosis indicators of cholestatic mice. The proteomics indicated that 460 differentially expressed proteins (DEPs) were identified among control, model, and model treated with high-dose YCZFD groups. Enrichment analyses of these DEPs revealed that YCZFD influenced multiple pathways, including PI3K-Akt, focal adhesion, ECM-receptor interaction, glutathione metabolism, and steroid biosynthesis pathways. The expression of platelet derived growth factor receptor beta (PDGFRß), a receptor associated with the PI3K/AKT and focal adhesion pathways, was upregulated in the livers of cholestatic mice but downregulated by YCZFD. The effects of YCZFD on the expression of key proteins in the PDGFRß/PI3K/AKT pathway were further confirmed in mice and transforming growth factor-ß-induced hepatic stellate cells. We uncovered seven plant metabolites (chlorogenic acid, scoparone, isoliquiritigenin, glycyrrhetinic acid, formononetin, atractylenolide I, and benzoylaconitine) of YCZFD that may regulate PDGFRß expression. Conclusion: YCZFD substantially protects against DDC-induced CLF mainly through regulating the PDGFRß/PI3K/AKT signaling pathway.

Identification of Yinchenwuling fang's active components and hepatoprotective effects against cholestatic liver damage induced by alpha-naphthyl isothiocyanate in mice.

Yinchenwuling Fang (YCWLF), a famous traditional Chinese medicine, has been used clinically for cholestatic liver disease treatment. However, quantification analysis for YCWLF components and their pharmacological effects remains largely unknown. Therefore, we aimed to determine the YCWLF components and their activities. Quantification analysis of 12 YCWLF components was performed using a comprehensive ultra-performance liquid chromatography (UPLC) coupled with the triple-quadrupole mass spectrometry method. Then, the anti-cholestasis effect and potential mechanism of YCWLF were performed in a mouse model induced by alpha-naphthyl isothiocyanate (ANIT). YCWLF decreased serum biochemical indicators (ALT, AST, ALP, TBA, TBIL, and DBIL) and ameliorated liver tissue damage in cholestatic mice. Mechanically, YCWLF increased the expression of the farnesoid X receptor (FXR) and its downstream efflux transporters and metabolic enzyme genes, reversed the disordered homeostasis of bile acids, and decreased cholestatic liver injury. Based on the important role of FXR in YCWLF amelioration on cholestasis, a dual-luciferase assay was used to screen the potential agonist of FXR from 12 YCWLF components. Chlorogenic acid, 4-hydroxyacetophenone, scoparone, atractylenolide Ⅰ, atractylenolide Ⅱ, and alisol B 23-acetate exhibited an activity effect of FXR. This study provides novel a therapeutic mechanism and potential active compounds of YCWLF on cholestatic liver injury.

Numerical investigation of the effect of the opening mode on the pressure relief process of engine nacelle.

The pressure relief door (PRD) is a vital structure to ensure the safety and reliability of the engine. This paper established a zero-dimensional transient simulation mathematical model to study the plenum compartment pressure threshold and maximum opening angle effects on the nacelle pressure relief process under different opening modes. Then, a computational fluid dynamics model verified by experimental literature data was used to simulate the nacelle pressure relief process and to determine the influence of two different opening modes on the force and discharge characteristics of the PRD. The results of this study show that different opening modes strongly impact the nacelle pressure relief process. Reducing the nacelle compartment pressure threshold of the PRD opening can reduce the time required for the pressure relief process to reach the equilibrium stage. Reducing the maximum opening angle may increase the nacelle compartment pressure during the equilibrium stage. In addition, under the same nacelle compartment pressure thresholds and maximum opening angles, the pressure relief process under the vertical opening mode can reach a lower nacelle compartment pressure during the pressure relief equilibrium stage compared to that under the horizontal opening mode. Therefore, the vertical opening mode is better than the horizontal opening mode. This paper provides two lower calculation costs and high accuracy research models for studying the nacelle pressure relief process.

Solubilities of CO2, O2 and N2 in rocket propellant 5 under low pressure.

The static method of isochoric saturation was used to measure the solubilities of CO2, O2 and N2 in rocket propellant 5 (RP5) at temperatures ranging from 253.15 to 323.15 K in 10 K intervals and pressures ranging from 0 to 120 kPa. The measurement accuracy of the constructed experimental setup was verified by measuring the solubility of CO2 in water. The relative expanded uncertainty (k = 2) in the solubility data was less than 4.0%. The solubilities of CO2, O2 and N2 in RP5 increased with pressure. As the temperature increased, the solubility decreased for CO2 solubility and increased for O2 and N2. Henry's constants for the three gases in RP5 decreased over the experimental temperature and pressure ranges in the order of N2 > O2 > CO2. The measured solubilities of CO2, O2 and N2 could be fitted with a modified Krichevsky-Kasarnovsky equation, and the maximum deviation between the measured and calculated data was less than 8.04%, 7.03% and 6.18%, respectively.