The multi-targeted kinase inhibitor sunitinib induces apoptosis in colon cancer cells via PUMA

Constitutive activation of pro-survival kinases has become a promising target of small molecules with an increasing interest in developing multi-targeted agents. The mechanisms underlying the responsiveness to most agents targeting cancer specific survival pathways are still poorly understood but critical for their clinical application. In this study, we found that sunitinib, a small molecule inhibitor of multiple tyrosine kinases including VEGFRs and PDGFRs induces apoptosis and inhibits cell growth in colon cancer cells in cell culture and xenograft models via the BH3-only protein PUMA. Sunitinib treatment induced PUMA transcription via the AKT/FoxO3a axis. PUMA, BH3 mimetics, or 5-Flurourical sensitized colon cancer cells to sunitinib-induced apoptosis. Furthermore, PUMA was induced by sunitinib treatment in xenograft tumors, and deficiency in PUMA significantly suppressed the anti-tumor effects of sunitinib. Our study suggests that PUMA-mediated apoptosis is important for the therapeutic responses to sunitinib, and activation of the mitochondrial pathway by BH3 mimetics or PUMA manipulation may be useful for improving the antitumor activity of sunitinib. Modulation of PUMA and selective Bcl-2 family members might be potential biomarkers for predicting sunitinib responses. © 2012 Sun et al

Association of multiple blood metals with thyroid function in general adults: A cross−sectional study

IntroductionThyroid function has a large impact on humans’ metabolism and is affected by iodine levels, but there is a scarcity of studies that elucidate the association between thyroid function and other elements.MethodsWe performed a cross-sectional study on 1,067 adults to evaluate the associations of the common essential metals with thyroid function in adults living in an iodine-adequate area of China. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and blood metals (zinc, iron, copper, magnesium, manganese, and calcium) were measured. Further, the thyroid hormone sensitivity indexes, FT3:FT4 ratio, and thyrotropin T4 resistance index (TT4RI) were calculated. Linear regression, quantile g-computation, and Bayesian kernel machine regression methods were used to explore the association of metals with thyroid function.ResultsWe found that the TSH levels correlated with copper (negative) and zinc (positive). Iron and copper were positively associated with FT3 and FT4 levels, respectively. Iron (positive) and copper (negative) were correlated with the FT3:FT4 ratio. Furthermore, we found that manganese was inversely correlated with TT4RI, while zinc was positively correlated.DiscussionOur findings suggest that manganese, iron, copper, and zinc levels were strongly correlated with thyroid function, and patients with thyroid disorders are recommended to measure those metals levels

Accumulation Characteristics of Metals and Metalloids in Plants Collected from Ny-Ålesund, Arctic

Toxic elements can be transported to polar regions by long-range atmospheric transport from mid and low latitudes, leading to enrichment of elements in the polar environment, especially in the Arctic. The plants can be ideal bioindicators of element contamination in environments, but information on the element enrichment and sources of plants remains limited in polar regions. Here, concentrations of 15 metals and metalloids (Pb, Ni, Cr, Cu, Co, As, Cd, Sb, Hg, Se, Fe, Zn, Mn, Al, and Ti) in six species of plants, Deschampsia caespitosa (Tufted Hair Grass), Puccinellia phryganodes (Creeping Alkaligrass), Saxifraga aizoides (Yellow Mountain Saxifrage), Dicranum angustum (Dicranum Moss), Salix Polaris (Polar Willow), and Cerastium arcticum (Arctic Mouse-Ear Chickweed), collected from Ny-Ålesund, the Arctic, were determined, and enrichment and sources of elements were assessed. Results show that element concentrations vary in different plant species, and element levels in D. angustum and C. arcticum are generally higher. In spatial terms, elevated element concentrations were found near residential areas, while low element levels were present at the sites far from settlement points. Enrichment assessment shows that Cd, Hg, and Zn are the most enriched elements, with enrichment factors above 30, suggesting sources other than soil dust control their concentrations. Principal component analysis (PCA) showed that the extracted three components can explain 82% of the total variance in element concentrations. The elements Ni, Cr, As, Sb, Fe, Al, Ti, and to a lesser extent Co are highly loaded in PC1, possibly associated with continental crust particles. PC2 is closely correlated with Cd, Se, Mn, Cu, and Zn, while Hg and Pb have high loadings on PC3. The elements highly loaded on PC2 and PC3 are likely associated with pollutants from atmospheric transportation. Together with enrichment assessment, the investigated plants have a great potential for monitoring atmospheric Cd, Hg, and Zn pollution in Ny-Ålesund, and D. angustum and D. caespitosa are the more sensitive species. The results would be of significance for monitoring element contamination in the pristine Arctic environments using the bioindicator plants

Simulation Analysis of the Characteristics of Layered Cores during Pulse Decay Tests

The permeability of low-permeability cores is generally measured using a pulse decay method. The core of low-permeability rocks, such as shale, often has a layered structure. The applicability of pulse decay testing for layered cores is not clear. In this study, the performance of the pulse decay method on layered cores was comprehensively investigated. Numerical simulations were conducted to investigate the influence of the interlayer permeability ratio, storativity ratio, layer thickness, interlayer location, and number of layers on the pulse decay pressure and pressure derivative curves, as well as the permeability obtained from pulse decay testing. The results revealed that the pressure curves of layered cores exhibit distinct differences from those of homogeneous cores if the upstream permeability is larger than the downstream one. The pressure derivative curve shows more inclined or horizontal straight-line segments than in the homogeneous case. The shapes of the pressure and pressure derivative curves are affected by the upstream and downstream positions of the core, but the tested permeability is not affected. The tested permeability differs from the equivalent model permeability, with an error of up to 22%. If the number of layers is not less than 10, the permeability obtained from the pulse decay test is consistent with that of the equivalent model. These differences are influenced by the interlayer permeability ratio, storativity ratio, layer thickness, interlayer location, and number of layers. To improve the accuracy of permeability analysis in pulse decay testing for layered cores, curve fitting using the characteristics of the pressure derivative curve can be employed

Prognostic value of the albumin-bilirubin score in patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare life-threatening systemic disease. This study aimed to assess the prognostic value of pretreatment albumin-bilirubin (ALBI). We retrospectively analyzed 168 non-Hodgkin lymphoma-associated secondary hemophagocytic lymphohistiocytosis (NHL-sHLH) patients with hepatic injuries. Multivariable logistic/Cox models and restricted cubic spline models were conducted to evaluate the relationships between the ALBI score and short- and long-term survival. Among 168 adult NHL-sHLH patients, 82 (48.8%) patients died within 30 days after admission, and 144 (85.7%) patients died during the follow-up period. Multivariable logistic/Cox regression model indicated that ALBI grade could be an independent risk factor for predicting the prognosis of patients with 30-day mortality and overall survival (odds ratios [OR]30 days 5.37, 95% confidence interval 2.41-12.64, P < 0.001; hazard ratios [HR]OS 1.52, 95% confidence interval 1.06-2.18, P = 0.023), respectively. The restricted cubic spline curve displayed a linear and positive relationship between the ALBI score and risk of mortality (P for nonlinearity =0.503). Furthermore, receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for predicting mortality by integrative analysis of the ALBI score and ferritin was significantly improved compared to the ALBI score (AUC 30 days: 0.820 vs 0.693, P = 0.001; AUC1 year: 0.754 vs 0.681, P = 0.043) or ferritin (AUC30 days: 0.820 vs 0.724, P = 0.005; AUC1 year: 0.754 vs 0.658, P = 0.031) alone. The ALBI score could be a useful indicator of short and long-term survival for NHL-sHLH patients with hepatic injuries

Steganalysis of Adaptive Multi-Rate Speech Based on Extreme Gradient Boosting

Steganalysis of adaptive multi-rate (AMR) speech is a hot topic for controlling cybercrimes grounded in steganography in related speech streams. In this paper, we first present a novel AMR steganalysis model, which utilizes extreme gradient boosting (XGBoost) as the classifier, instead of support vector machines (SVM) adopted in the previous schemes. Compared with the SVM-based model, this new model can facilitate the excavation of potential information from the high-dimensional features and can avoid overfitting. Moreover, to further strengthen the preceding features based on the statistical characteristics of pulse pairs, we present the convergence feature based on the Markov chain to reflect the global characterization of pulse pairs, which is essentially the final state of the Markov transition matrix. Combining the convergence feature with the preceding features, we propose an XGBoost-based steganalysis scheme for AMR speech streams. Finally, we conducted a series of experiments to assess our presented scheme and compared it with previous schemes. The experimental results demonstrate that the proposed scheme is feasible, and can provide better performance in terms of detecting the existing steganography methods based on AMR speech streams

Characterterization of multi-scale nanosilver paste reinforced with SIC particles

Nanosilver paste with high operation temperature and low sintering temperature has attracted more and more attention for its promising application in high power devices. In this paper, the thermal properties of multi-scale nanosilver paste composed of nanometer and micrometer silver particles, and Ag-coated SiC particles were investigated. The thermal conductivity of multi-scale nanosilver paste increases with the increasing amount of SiC particles with Ag coating. The maximum value of Vickers hardness for multi-scale nanosilver paste with 0.5 wt.% Ag-coated SiC particles were 24