Microtubules as a Critical Target for Arsenic Toxicity in Lung Cells in Vitro and in Vivo

To understand mechanisms for arsenic toxicity in the lung, we examined effects of sodium m-arsenite (As3+) on microtubule (MT) assembly in vitro (0–40 µM), in cultured rat lung fibroblasts (RFL6, 0–20 µM for 24 h) and in the rat animal model (intratracheal instillation of 2.02 mg As/kg body weight, once a week for 5 weeks). As3+ induced a dose-dependent disassembly of cellular MTs and enhancement of the free tubulin pool, initiating an autoregulation of tubulin synthesis manifest as inhibition of steady-state mRNA levels of βI-tubulin in dosed lung cells and tissues. Spindle MT injuries by As3+ were concomitant with chromosomal disorientations. As3+ reduced the binding to tubulin of [3H]N-ethylmaleimide (NEM), an -SH group reagent, resulting in inhibition of MT polymerization in vitro with bovine brain tubulins which was abolished by addition of dithiothreitol (DTT) suggesting As3+ action upon tubulin through -SH groups. In response to As3+, cells elevated cellular thiols such as metallothionein. Taxol, a tubulin polymerization agent, antagonized both As3+ and NEM induced MT depolymerization. MT–associated proteins (MAPs) essential for the MT stability were markedly suppressed in As3+-treated cells. Thus, tubulin sulfhydryls and MAPs are major molecular targets for As3+ damage to the lung triggering MT disassembly cascades

Influence of Polymer Matrices on the Tensile and Impact Properties of Long Fiber-Reinforced Thermoplastic Composites

To investigate the influence of polymer matrices on the tensile and impact properties of long fiber-reinforced thermoplastic (LFT) composites, composites of long basalt fiber-reinforced thermoplastic were developed in this work. Two types of polyethylene, namely 8008 and 100S, and two types of polyethylene, namely C4220 and K8303, were chosen as the matrices. The fiber volume fractions were set as 2.8%, 5.9%, 8.1%, and 10.6%. The melt flow index (MFI), crystallinity, tensile properties, impact strength, and fracture morphology of the neat polymers and the corresponding composites were tested. The composites of 8008 showed the highest tensile strength since neat 8008 showed a much higher MFI value and crystallinity. The composites of 8008 and K8303 showed a much higher tensile modulus since the neat thermoplastic showed a higher tensile modulus than the other two composites. The polymer toughness was the factor that determined whether the polymer could be toughened by fibers. Moreover, the interfacial shear strength was calculated and compared with the matrix shear strength, based on which fracture modes of the LFT were predicted. Effective methods were proposed for further improvement of the mechanical properties. The results of this paper were essential for attaining the anticipated properties when designing LFT composites

Exploring the Joint Impacts of Natural and Built Environments on PM2.5 Concentrations and Their Spatial Heterogeneity in the Context of High-Density Chinese Cities

Air pollution in China has attracted wide interest from the public and academic communities. PM2.5 is the primary air pollutant across China. PM2.5 mainly comes from human activities, and the natural environment and urban built environment affect its distribution and diffusion. In contrast to American and European cities, Chinese cities are much denser, and studies on the relationships between urban form and air quality in high-density Chinese cities are still limited. In this paper, we used the ordinary least square (OLS) and geographical weighted regression (GWR) models, selected an already high-density city, Shenzhen, as the study area, and explored the effects of the natural and built environments on air pollution. The results showed that temperature always had a positive influence on PM2.5 and wind speed had a varied impact on PM2.5 within the city. Based on the natural factors analysis, the paper found that an increase in the floor area ratio (FAR) and road density may have caused the increase in the PM2.5 concentration in the central city. In terms of land use mix, land use policies should be adopted separately in the central city and suburban areas. Finally, in terms of spatial heterogeneity, the GWR models achieved much better performances than the global multivariate regression models, with lower AICc and RMSE values and higher adjusted R2 values, ultimately explaining 60% of the variance across different city areas. The results indicated that policies and interventions should be more targeted to improve the air environment and reduce personal exposure according to the spatial geographical context

Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival from Colon Cancer: A United States Population-Based Study

© 2016 AGA Institute. Background & Aims We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage. Methods We collected data from the Surveillance, Epidemiology, and End Results-Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed up through 2011. Three sets of 6190 white patients were matched sequentially, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age; sex; diagnosis year; and Surveillance, Epidemiology, and End Results registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a subcohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. Results After patients were matched for demographic variables, the absolute 5-year difference in survival between black and white patients was 8.3% (white, 59.2% 5-y survival; blacks, 50.9% 5-y survival) (P \u3c.0001); this value decreased significantly, to 5.0% (P \u3c.0001), after patients were matched for tumor presentation, and decreased to 4.9% (P \u3c.0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to an 11.1% difference) vs early stage cancer (stages I or II, up to a 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5-year racial survival disparity was 7.7% after demographic match, which was less than the 8.3% observed in the complete cohort. This reduction likely was owing to the differences between the subcohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% (P =.0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% (P =.090) after tumor presentation match, but was not reduced further after treatment match. Conclusions We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been affected more strongly by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage vs early-stage cancer

Data_Sheet_1_Effects of a natural nutritional supplement on immune cell infiltration and immune gene expression in exercise-induced injury.docx

Inflammatory immune response plays a key role in exercise-induced injury and healing; however, the relevant regulatory mechanisms of immune infiltration in exercise-induced injuries remain less studied. In the present study, a highly efficient system for screening immunity-related biomarkers and immunomodulatory ability of natural nutritional supplements was developed by integrating intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. The findings demonstrated that resting natural killer cells showed a higher rate of infiltration after exercise, whereas naive B cells and activated dendritic cells showed higher rate of infiltration before exercise. Four key genes, namely PRF1, GZMB, CCL4, and FASLG, were associated with exercise-induced injuries and inflammatory immune response. In total, 26 natural compounds including echinacoside, eugenol, tocopherol, and casuariin were predicted by using the HERB databases. Molecular docking analysis showed that GZMB, FASLG, and CCL4 bound to echinacoside. In vivo experiments in mice showed that after 30 min swimming, natural killer (NK) cells showed high infiltration rates, and the key genes (GZMB, PRF1, FASLG, and CCL4) were highly expressed; however, echinocandin significantly reduced the level of NK cells and decreased the expression of the four key genes post exercise. This natural nutritional supplement may act to protect against inflammatory injury after exercise by suppressing specific immune infiltration.</p