Investigating the pharmacological mechanism of Zhengyuan jiaonang for treating colorectal cancer via network pharmacology analysis and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhengyuan jiaonang (ZYJN) is a traditional Chinese patent medicine (CPM) used in China for adjuvant cancer therapy, which has been proved to have anti-fatigue effects. AIM OF STUDY: The study aims to investigate the antitumor effects of ZYJN and its underlying mechanisms using subcutaneous transplant CT26 model. MATERIALS AND METHODS: Fingerprint analysis of ZYJN was performed using high performance liquid chromatography. The potential targets of ZYJN were predicted using bioinformatic analysis, which were further validated by Western Blot assay. Subcutaneous transplant CT26 model was used to evaluate the antitumor effects of ZYJN. The effects of ZYJN on the tumor immune microenvironment were investigated by flow cytometry. Transparent imaging was used to investigate the effects of ZYJN on fibrosis and angiogenesis. RESULTS: ZYJN could inhibit colorectal cancer growth when administered alone or in combination with 5-FU. The combination of ZYJN and 5-FU could significantly increase the serum level of albumin (ALB) and decrease the serum level of aspartate aminotransferase (AST). In addition, the combination of ZYJN at 0.75 g/kg and 5-FU significantly decreased the serum level of vascular endothelial growth factors (VEGF) and inhibited the angiogenesis of CT26 cancer. The combination of ZYJN at 1.50 g/kg and 5-FU could promote the fibrosis process of CT26 cancer. Additionally, combination of ZYJN and 5-FU could significantly increase the percentage of tumor-infiltrating T cells and CD4+ T cells in the late stage of CT26 model, while ZYJN at 1.50 g/kg increased the percentage of NK cells as well as CD8+ T cells in the early stage of CT26 model. Western Blot analysis revealed that administration of ZYJN at 0.75 g/kg reduced the expression of PI3K-p110α, CDK1, CCNB1 and MMP-9, and inhibited the phosphorylation of Akt (Thr308). CONCLUSIONS: ZYJN could inhibit the tumor growth of CT26 colorectal cancer by promoting tumor fibrosis, suppressing angiogenesis, migration, and invasion and modulating the tumor immune microenvironment. ZYJN enhanced the efficacy and reduced the toxicity of chemotherapy drugs in combination therapy. Our findings provide evidence for the clinical application of ZYJN in cancer treatment.

Unveiling the intrinsic role of water in the catalytic cycle of formaldehyde oxidation: a comprehensive study integrating density functional theory and microkinetic analysis.

Previous research is predominantly in consensus on the reaction mechanism between formaldehyde (HCHO) and oxygen (O2) over catalysts. However, water vapor (H2O) always remains present during the reaction, and the intrinsic role of H2O in the oxidation of HCHO still needs to be fully understood. In this study, a single-atom catalyst, Al-doped C2N substrate, Al1/C2N, can be adopted as an example to investigate the relationship and interaction among O2, H2O, and HCHO. Density functional theory (DFT) calculations and microkinetic simulations were carried out to interpret the enhancement mechanism of H2O on HCHO oxidation over Al1/C2N. The outcome demonstrates that H2O directly breaks down a surface hydroxyl group on Al1/C2N, considerably lowering the energy required to form crucial intermediates, thus promoting oxidation. Without H2O, Al1/C2N cannot effectively oxidize HCHO at ambient temperature. During oxidation, H2O takes the major catalytic responsibility, delaying the entrance of O2 into the reaction, which is not only the product but also the crucial reactant to initiate catalysis, thereby sustaining the catalytic cycle. Moreover, this study predicts the catalytic behavior at various temperatures and presents feasible recommendations for regulating the reaction rates. The oxidation mechanism of HCHO is explained at the molecular level in this study, emphasizing the intrinsic role of water on Al1/C2N, which fills in the relevant studies for HCHO oxidation on two-dimensional carbon materials.

Migration and redistribution of LNAPL in inclined stratified soil media.

Leakage of light non-aqueous phase liquid (LNAPL) into soil can cause serious environmental issues. In this study, a two-dimensional device with adjustable dip angles was designed to investigate the migration and redistribution of LNAPL in natural inclined stratified soil media by the light transmission visualization (LTV) technology. The captured experimental images were processed to obtain the diesel distribution based on gray value which could represent the LNAPL saturation distribution. LNAPL may not be able to penetrate through the fine-coarse interface due to the capillary barrier effects. In this case, the vertical and horizontal migration distances (V and H), contaminated area (S), as well as deviation angle (γ) of centroid increased with the dip angle. Increasing the leakage amount to more than 30 mL would result in LNAPL breakthrough at the 10°-inclined interface, leading to much larger V, H, S, and γ than those at 10 mL, while 20-mL LNAPL failed to break through. In the latter case, a lower leakage rate than 10 mL/min would cause larger H and γ but similar V or S in the long term. This study could enrich the understanding of LNAPL contamination in vadose zone, providing reference for the prediction and treatment in realistic inclined contaminated sites.