ZEB2 Mediates Multiple Pathways Regulating Cell Proliferation, Migration, Invasion, and Apoptosis in Glioma

BACKGROUND: The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. RESULTS: The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. CONCLUSION: Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells

Molecular dynamics simulations of organoclays and polymer nanocomposites

Understanding the interfacial interactions and structure is important to better design and manufacturing of nanoparticle-filled polymer nanocomposites. This paper presents our recent molecular dynamic studies on organically modified clays and polymer nanocomposites, including the swelling of clay minerals, molecular structure and dynamics in clay gallery, and interfacial interactions of polyurethane nanocomposites. The simulated results are in good agreement with the experimental measurements and observations. Quantitative analyses are made in atom density distribution, molecular tilt angle, order parameter, conformation, and mean squared displacement. Various layering structures (e.g., monolayer, bilayer, pseudo-trilayer and pseudo-quadrilayer) are observed in the gallery of organoclays, depending on the chain length of alkyl ammoniums and cationic exchangeable capacity of clays. In particular, the long alkyl chains do not lie flat within a single layer but interlace, and likely jump to the next layers. In polyurethane nanocomposite, the molecular interplays among clay surface, alkyl ammoniums and polyurethane chains lead to the absence of phase-separation of polyurethane, commonly observed in bulk polyurethane systems

Multiscale modeling and simulation of polymer nanocomposites

Polymer nanocomposites offer a wide range of promising applications because of their much enhanced properties arising from the reinforcement of nanoparticles. However, further development of such nanomaterials depends on the fundamental understanding of their hierarchical structures and behaviors which requires multiscale modeling and simulation strategies to provide seamless coupling among various length and time scales. In this review, we first introduce some computational methods that have been applied to polymer nanocomposites, covering from molecular scale (e.g., molecular dynamics, Monte Carlo), microscale (e.g., Brownian dynamics, dissipative particle dynamics, lattice Boltzmann, time-dependent Ginzburg–Landau method, dynamic density functional theory method) to mesoscale and macroscale (e.g., micromechanics, equivalent-continuum and self-similar approaches, finite element method). Then, we discuss in some detail their applications to various aspects of polymer nanocomposites, including the thermodynamics and kinetics of formation, molecular structure and dynamics, morphology, processing behaviors, and mechanical properties. Finally, we address the importance of multiscale simulation strategies in the understanding and predictive capabilities of polymer nanocomposites in which few studies have been reported. The present review aims to summarize the recent advances in the fundamental understanding of polymer nanocomposites reinforced by nanofillers (e.g., spherical nanoparticles, nanotubes, clay platelets) and stimulate further research in this area

Evaluation of interaction forces between nanoparticles by molecular dynamics simulation

Molecular dynamics simulations are used to quantify the interaction forces between nanoparticles, which are critical to nanoparticle systems. It is shown that the fluctuation of surface atomic density and the dynamics of collisions significantly affect the interaction forces. As a result, the Hamaker method cannot accurately estimate the interaction forces for nanoparticles. The proposed approach offers an effective method for determining the interaction forces between nanoparticles

Numerical analysis of hydrocyclones with different vortex finder configurations

This paper presents a numerical study of the multiphase flow and performance of hydrocyclone by means of two-fluid model, with special reference to the effects of diameter, length and shape of vortex finder at a wide range of feed solids concentrations. The considered shapes include the conventional cylindrical style and the new conical and inverse conical styles. The simulation results are analysed with respect to cyclone flow and performance in term of cut size d50, water split, Ecart probable Ep and inlet pressure drop. It is shown that when vortex finder diameter or shape varies, a compromised optimum performance can be identified, resulting in relatively small inlet pressure drop, Ep, and water split. Both d50 and Ep are more sensitive to feed solids concentration than inlet pressure drop and water split. Overall, the effect of vortex finder length on the separation efficiency of particles is much less significant than diameter and shape, which shows opposite trends at low and high feed solids concentrations. All these results can be well explained using the predicted tangential and axial velocities and solid volume fraction

CFD study of the multiphase flow in classifying hydrocyclone : effect of cone geometry

This paper presents a numerical study of the gas–liquid– solid flow in hydrocyclones by a recently developed continuum-based multiphase flow model. The applicability of the model has been verified by a good agreement between the calculated and measured flow fields and separation efficiency (Kuang et al., 2012), and is used here to study the effect of cone length from a feed solids concentration of 4 to 30% (by volume). The numerical results show that for a standard design of cone section, decreasing cone length leads to the decrease of separation efficiency and the increase of inlet pressure drop for a given feed solids concentration. It is also shown that the performance of the cyclone with a short cone section is very sensitive to feed solids concentration

Numerical analysis of hydrocyclones with different conical section designs

Hydrocyclones generally follow a conventional design and may have some limitations on separation performance. This paper presents a numerical study of hydrocyclones with different conical configurations by a recently developed computational fluid dynamics method. The feed solids concentration considered is up to 30% (by volume), which is well beyond the range reported before. The numerical results show that the cyclone performance is sensitive to both the length and shape of the conical section, as well as the feed solids concentration. A longer conical section length leads to decreased inlet pressure drop, cut size d50, and Ecart probable Ep, and at the same time, an increased water split (thus larger by-pass effect). When conical shape varies from the concave to convex styles gradually, a compromised optimum performance is observed for the cyclone with a convex cone, resulting in a minimum Ep and relatively small inlet pressure drop and water split. Almost all these effects are pronounced with increasing feed solids concentration. Based on the numerical experiments, a new hydrocyclone featured with a long convex cone is proposed. It can improve the performance of the conventional cyclone at all the feed solids concentrations considered

Computational study of the multiphase flow and performance of hydrocyclones : effects of cyclone size and spigot diameter

This paper presents a numerical study of multiphase flow in hydrocyclones with different configurations of cyclone size and spigot diameter. This is done by a recently developed mixture multiphase flow model. In the model, the strong swirling flow of the cyclone is modeled using the Reynolds stress model. The interface between liquid and air core and the particle flow are both modeled using the so-called mixture model. The solid properties are described by the kinetic theory. The applicability of the proposed model has been verified by the good agreement between the measured and predicted results in a previous study. It is here used to study the effects of cyclone size and spigot diameter when feed solids concentration is up to 30% (by volume), which is well beyond the range reported before. The flow features predicted are examined in terms of the flow field, pressure drop, and amount of water split to underflow, separation efficiency and underflow discharge type. The simulation results show that the multiphase flow in a hydrocyclone varies with cyclone size or spigot diameter, leading to a different performance. A smaller cyclone results in an increased cut size, a decreased pressure drop and a sharper separation, and, at the same time, an increased water split (thus worse bypass effect) and a more possibly unstable operation associated with rope discharge, particularly at relatively high feed solids concentrations. Both large and small spigot diameters may lead to poor separation performance. Accordingly, an optimum spigot diameter can be identified depending on feed solids concentration. It is also shown that for all the considered hydrocyclones, a better separation performance and a smoother running state can be achieved by the operation at a lower feed solid concentration