Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Effect of different odors on the fighting behavior of weaning piglets after merging into a large pen.

In intensive pig production, the fighting behavior of weaning piglets after merging pens is relatively common. Fighting behavior not only easily causes injury in pigs but also affects the production performance of pigs. To reduce fighting behavior in farms, this study aimed to explore the possible effect of odorous substances on piglet fighting behavior after merging into a large pen. Six different sprays were tested: original creamy, cheese flavor, orange flavor, truffle, vanilla and pigpen flavor. In each experiment, two groups were set (one odor-sprayed and no sprayed control), and 12 pigs were used per group. After mixing, the frequency of occurrence of various piglet behaviors in different pens was recorded. During this period, salivary cortisol levels and skin lesion scores were evaluated. As a result, the piglets sprayed with the original creamy, cheese flavor and vanilla substances obtained significantly higher average daily gain and feed intake and showed a significantly lower incidence of fighting behavior, and the skin lesion score and salivary cortisol of piglets were also reduced significantly. All the other odorous substances had no significant effects on the fighting behavior and production performance of piglets.

The Anticancer Effect of Metformin Combined with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients with or Without Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

INTRODUCTION: Despite the growing evidence for the anticancer effect of metformin or its combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the efficacies and side effects of such strategies in non-small cell lung cancer (NSCLC) patients with or without type 2 diabetes mellitus (T2DM) are not well understood. This meta-analysis was performed to determine the efficacy and side effects of metformin combined with EGFR-TKIs (MET-EGFR-TKIs) for the treatment of NSCLC with or without T2DM. METHODS: PubMed and Cochrane Library databases were used to retrieve relevant studies through August 2020 using the keywords "metformin", "EGFR-TKIs" ("gefitinib" or "erlotinib" or "afatinib" or "icotinib" or "dacomitinib") and "lung cancer". The patients in the experimental group received MET-EGFR-TKIs, while those in the control group received only EGFR-TKIs. The outcome analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Random-effect models and fixed-effect models were used to estimate the combined hazard ratio (HR) and odds ratio (OR) depending on the data heterogeneity. Three studies (including 1996 patients) were included in the current meta-analysis. RESULTS: There were significant differences in PFS (HR 0.84; 95% confidence interval (CI) 0.75-0.95; P = 0.004) and OS (HR 0.77; 95% CI, 0.50-1.04; P < 0.001) between the MET-EGFR-TKI and EGFR-TKI groups. Although the ORR (OR 1.38; 95% CI 0.66-2.88; P = 0.105) and DCR (OR 2.61, 95% CI 0.68-9.95, P = 0.160) were improved, there was no statistical significance. OS subgroup analysis showed that the combination was more effective in NSCLC with T2DM than in NSCLC without T2DM (HR 0.84; 95% CI 0.74-0.95; P < 0.005). CONCLUSIONS: MET-EGFR-TKIs provided benefits for PFS and OS, and OS subgroup analysis showed that patients with NSCLC with T2DM received greater benefit than NSCLC patients without T2DM. However, further large-scale, well-designed randomized controlled trials (RCTs) are warranted to confirm the findings in the present investigation.

Optimizing electronic structure of porous Ni/MoO2 heterostructure to boost alkaline hydrogen evolution reaction.

Heterostructure engineering is an efficient strategy to synergisticallyimprove electrocatalytic activity. In this work, Ni/MoO2 heterojunction nanorods with porous structure self-supported on nickel foam (NF) are elaborately designed through a facile solution-evaporationmethod followed by a thermal reduction process. Prominently, the optimal electrocatalyst Ni/MoO2@NF-E delivers an exceptionally low overpotential of 19 mV at the current density of 10 mA cm-2 and a small Tafel slope of 52.3 mV dec-1 toward the hydrogen evolution reaction (HER) in alkaline solution. Concurrently, Ni/MoO2@NF-E also maintains excellent stability after 120 h of electrolysis or 5000 cyclic voltammetry cycles. The experimental and density functional theory (DFT) results indicate that the enhanced HER performance of Ni/MoO2@NF-E should be ascribed to the porous structure in the Ni/MoO2 nanorods providing more active catalytic site, the moderate Gibbs free energy of hydrogen adsorption (ΔGH*), as well as strong synergistic effect between Ni and MoO2. This work provides an efficient route for developing HER electrocatalysts in alkaline media.

The Delineation and Ecological Connectivity of the Three Parallel Rivers Natural World Heritage Site.

Landscape connectivity refers to the degree of continuity between the spatially structured units of a landscape. Ecological connectivity can characterise the degree to which ecological functional areas are connected in terms of function and ecological processes. In this study, the landscape pattern index and ecosystem service values were used to evaluate the ecological functional resistance of each landscape type, taking the Three Parallel Rivers Natural World Heritage Site as an example and the habitat distribution and population size of the Yunnan snub-nosed monkey as a reference. The minimum cost distance model, combined with the barrier impact index (BEI) and ecological connectivity index (ECI), was used to determine the degree of barrier impact on the study area and the ecological connectivity of the core reserve of the heritage site in both 2000 and 2020. The resistances of the different land types and landscape heterogeneity to the ecological function of species migration between the core protected areas of the heritage site were, in descending order, those of the forest, shrubs and grass, water, unused land, cultivated land, and built-up land. In 2020, the study area had a large BEI, with areas such as built-up areas, major roads, the sides of large rivers, and arable land being significant contributors to the blockage of landscape connectivity. The overall landscape connectivity in the study area was generally low, with clear spatial differentiation and a three-column parallel distribution pattern influenced by the topography and landscape. With the adjustment of the core reserve boundaries of the heritage site, the proportion of areas with high connectivity (ECI = 4-5) increased from 11.31% in 2000 to 34.36% in 2020. This increased landscape connectivity was conducive to the migration and reproduction of large terrestrial animals, such as the Yunnan snub-nosed monkey, with increasing numbers of populations and individuals. This study provides theoretical and methodological insights into the delineation and conservation of natural heritage sites and landscape connectivity.

Modulation of Growth Performance and Intestinal Microbiota in Chickens Fed Plant Extracts or Virginiamycin.

In this study, the effects of plant extracts (PEs) and virginiamycin (VIRG) on broiler growth performance, as well as on host intestinal microbiota composition and function were investigated. A total of 288 one-day-old male Cobb broiler chickens were randomly divided into four treatment groups (with six replicates per group). The duodenal, ileal, and cecal content of six broilers per treatment group after 14 and 28 days of treatment were sampled. This material was used for high-throughput Illumina sequencing of the V3-V4 region of the 16S rRNA gene. The results showed that chickens fed 400 mg/kg plant extracts (HPE group) had significantly higher average body weights at day 28 as compared to the control group (CT; P < 0.05), and lower feed-to-meat ratios over days 15-42 (P < 0.01). Within the HPE group at day 14, the relative abundances of two bacterial phyla and 10 bacterial genera increased significantly in the ileal microbiota, and the relative abundance of three bacterial phyla and four bacterial genera decreased. The relative abundance of the genus Lactobacillus in the cecal microbiota decreased from 21.48% (CT group) to 8.41% (fed 200 mg/kg PEs; LPE group), 4.2% (HPE group), and 6.58% (fed 30 mg/kg virginiamycin; VIRG group) after 28 days. In contrast, Faecalibacterium and unclassified Rikenellaceae increased in abundance in the HPE group (from 18 to 28.46% and from 10.83 to 27.63%, respectively), while Bacteroides (36.7%) and Lachnospiraceae increased in abundance in the VIRG group. PICRUSt function analysis showed that the ileal microbiota of the PE treatment groups were more enriched in genes related to the meolism of cofactors and vitamins. In addition, the cecal microbiotas of the LPE and HPE groups were enriched in genes predicted to encode enzymes within 15 and 20 pathways, respectively. These pathways included protein digestion and absorption, amino acid metabolism, lipid biosynthesis, lipopolysaccharide biosynthesis, the citrate cycle (TCA cycle), and lipoic acid metabolism. Similarly, the VIRG group was enriched in 55 metabolic pathways (17 in the duodenum, 18 in the ileum, and 20 in the cecum) on day 28 (P < 0.05). Thus, the results indicated that the observed increase in broiler growth performance after PE or VIRG supplementation might be attributed to an improvement in intestinal microbial composition and metabolic function.