Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets

The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a pro-tumor inflammatory microenvironment. Furthermore, in silico mutation studies and experimental validations led to a novel finding that concurrently targeting ceramide and PI3K/AKT pathway by chemical probes or marketed drugs achieves synergistic anti-cancer effects. Overall, our network model can guide further mechanistic studies on CAC and provide new insights into the design of combinatorial cancer therapies in a rational manner

The mechanisms of Yu Ping Feng San in tracking the cisplatin-resistance by regulating ATP-binding cassette transporter and glutathione S-transferase in lung cancer cells

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs

Free Cash Flows and Price Momentum

This study investigates the role of free cash flows and (cross-sectional and time-series) price momentum in predicting future stock returns. Past returns and free cash flows each positively predict future stock returns after controlling for the other, suggesting that cash flows and momentum both contain valuable and distinctive information about future stock returns. A strategy of buying past winners with high free cash flows and shorting past losers with low free cash flows significantly outperforms the traditional momentum trading strategy. The enhanced performance is not sensitive to investor sentiment, time variations, or transaction costs. Further analysis shows that the incremental cash flow effects are largely attributable to net distributions to equity/debt holders. Overall, our findings shed light on the role of corporate fundamentals in technical trading strategies

The effect of parenting styles on depressive symptoms among Chinese college students: The role of subjective well-being and Taq1A polymorphism

Based on different susceptibility models, the current study constructed a moderated mediation model to explore the influence of parenting style on college students’ depressive symptoms. A total of 301 college students (74 boys and 227 girls) participated in this study. Subjective well-being played a mediating role in the effect of parenting style on depressive symptoms. The DRD2 Taq1A polymorphism moderated the direct pathway in the PPS (positive parenting style) model and the second half of the mediating pathway in the NPS (negative parenting style) model. The findings suggest that the Taq1A polymorphism allele A2 is the plasticity gene for depression, and the A2A2 homozygous gene is the most sensitive to environmental stimuli

The effect of parent-child relationship and Educational involvement on adolescent NSSI: the role of perceived stress and meaning in life

This study explored the influence of parent‒child relationship and parental educational involvement on adolescent NSSI. Based on ecosystem theory and the diathesis stress model, A follow-up survey was conducted with 771 adolescents (age = 15.24 ± 1.66 years) using questionnaire method (The Deliberate Self-Harm Inventory, the Parent-child Intimacy Questionnaire, The Primary School Students’ Parents’ Educational Involvement Behavior Scale, the Perceived Stress Scale and Chinese version of the Meaning in Life Questionnaire). The results showed that (1) Adolescents with a high parent‒child relationship and high educational involvement had a lower level of perceived stress than those with a low parent‒child relationship and low educational involvement. Compared to individuals with a low parent‒child relationship and high educational involvement, individuals with a high parent‒child relationship and low educational involvement showed a lower level of perceived stress. (2) Perceived stress partially mediated the relationship between the parent‒child relationship and educational involvement and adolescent NSSI. (3) Meaning in life moderated the influence of perceived stress on adolescent NSSI. Specifically, with the increase in meaning in life, the influence of perceived stress on NSSI gradually decreased

Serum miR-200c and miR-371-5p as the Useful Diagnostic Biomarkers and Therapeutic Targets in Kawasaki Disease

Kawasaki disease (KD) has complexly clinical features and laboratory parameters and there is no definitive biomarker for this disease and the therapy of KD also is complex and uncertain. In this study, 102 KD patients and 80 healthy controls were enrolled in this study and the serum microRNAs were detected by qRT-PCR. The results showed that, compared with KD patients with a good response to high-dose intravenous immunoglobulin (IVIG) therapy, serum miR-200c and miR-371-5p were significantly higher in KD patients with no response to IVIG therapy; compared with KD patients not needing plasma exchange, these two microRNAs were also significantly higher in KD patients needing plasma exchange. In addition, combination of serum miR-200c and miR-371-5p reflected obvious separation between KD patients and healthy controls or between KD patients with no response to IVIG therapy and KD patients with good response to IVIG therapy or KD patients needing plasma exchange and KD patients not needing plasma exchange. Finally, both serum miR-200c and miR-371-5p were also significantly lower in KD under different kinds of therapy. Therefore, serum miR-200c and miR-371-5p have ability as the useful diagnostic biomarkers and therapeutic targets in Kawasaki disease

Nature-inspired green method decorated MXene-based composite membrane for high-efficiency oil/water separation

Nature inspired 'green' method has been reported for the fabrication of nanoparticles from the plant derived polyphenol tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES). In present investigation, TA-APTES nanoparticles decorated MXene nanosheets were acted as active layers and TA-APTES@MXene composite membrane were constructed by vacuum self-assembly on cellulose acetate support in order to improve membrane performance. The modified membrane showed an excellent hydrophilicity with a water flux of 5990.11 L.m(-2).h(-1) at 0.1 MPa, which is 15 times higher than pure MXene membrane. Moreover, the removal ratios of three different types of oil/water emulsions (petroleum ether, lubricating oil and vegetable oil) were found to be more than 98%. More importantly, the highly oleophobic membrane surface maintained a relatively high separation performances after four consecutive cycles of performances. This investigation achieves a leap of MXene-based membrane materials from nano-to micro-scale, which provides valuable insights in the field of oil/water separation

Experimental Investigation on Short Concrete Columns Reinforced by Bamboo Scrimber under Axial Compression Loads

The paper presents bamboo scrimber bars as a reinforcing material instead of steel reinforcement in low-strength concrete columns. Twelve short concrete columns with different reinforcements are tested under axial compression load to study the axial compressive behavior of short concrete columns reinforced by bamboo scrimber. Three columns are reinforced concrete columns, and the other nine columns are bamboo scrimber reinforced concrete columns. The failure process, bearing capacity, axial deformation, and strain of the specimens are compared and analyzed. The results show that the bonding performance between the bamboo scrimber bars by surface treatment and low-strength concrete is excellent. In low-strength concrete columns, the material properties of bamboo bars play more thoroughly than those of steel bars. When the bamboo reinforcement ratio is increased, the concrete column ductility is significantly improved, but the bearing capacity of the concrete column is not increased. The bamboo scrimber bars with the size of 10 mm × 10 mm or 15 mm × 15 mm can be used as longitudinal bars of low-strength concrete columns. The ductility of the short concrete column with 2.56% bamboo scrimber reinforcement is close to that of the short concrete column with 0.72% steel reinforcement