Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

高岭土性质对催化裂化催化剂性能的影响

采用X射线荧光分析仪、X射线衍射仪、N2物理吸附仪、场发射扫描电子显微镜等仪器表征了苏州、广西和美国佐治亚州3个产地的高岭土，并以此3种高岭土为原料制备了模型催化裂化（FCC）催化剂，在ACE评价装置上对比了模型催化剂的反应性能。结果表明:苏州及广西高岭土主要组分为高岭石，佐治亚高岭土主要组分为地开石及珍珠陶土；苏州高岭土呈片状，还含有少量棒状颗粒；广西高岭土呈多层片状，晶粒粒径较大；佐治亚高岭土呈薄片状，晶粒粒径较小；3种高岭土制备的模型催化剂反应活性、Na2O及RE2O3质量分数相近；广西高岭土制备的模型催化剂具有最大的孔体积和磨损指数，但比表面积最小，具有较强的重油转化能力，其目标产物（液化气+汽油）和副产物（干气+焦炭）收率都高于苏州、佐治亚高岭土制备的催化剂的。     

Designing amorphous formulations of polyphenols with naringin by spray-drying for enhanced solubility and permeability

Naringin (NAR), a major flavanone (FVA) glycoside, is a component of food mainly obtained from grapefruit. We used NAR as a food additive to improve the solubility and permeability of hydrophobic polyphenols used as supplements in the food industry. The spray-dried particles (SDPs) of NAR alone show an amorphous state with a glass transition temperature (T_g) at 93.2 °C. SDPs of hydrophobic polyphenols, such as flavone (FVO), quercetin (QCT), naringenin (NRG), and resveratrol (RVT) were prepared by adding varying amounts of NAR. All SDPs of hydrophobic polyphenols with added NAR were in an amorphous state with a single T_g, but SDPs of hydrophobic polyphenols without added NAR showed diffraction peaks derived from each crystal. The SDPs with NAR could keep an amorphous state after storage at a high humidity condition for one month, except for SDPs of RVT/NAR. SDPs with NAR enhanced the solubility of hydrophobic polyphenols, especially NRG solubility, which was enhanced more than 9 times compared to NRG crystal. The enhanced solubility resulted in the increased membrane permeability of NRG. The antioxidant effect of the hydrophobic NRG was also enhanced by the synergetic effect of NAR. The findings demonstrated that NAR could be used as a food additive to enhance the solubility and membrane permeability of hydrophobic polyphenols.     

Maximum likelihood-based adaptive differential evolution identification algorithm for multivariable systems in the state-space form

Parameter estimation plays an important role in the field of system control. This article is concerned with the parameter estimation methods for multivariable systems in the state-space form. For the sake of solving the identification complexity caused by a large number of parameters in multivariable systems, we decompose the original multivariable system into some subsystems containing fewer parameters and study identification algorithms to estimate the parameters of each subsystem. By taking the maximum likelihood criterion function as the fitness function of the differential evolution algorithm, we present a maximum likelihood-based differential evolution (ML-DE) algorithm for parameter estimation. To improve the parameter estimation accuracy, we introduce the adaptive mutation factor and the adaptive crossover factor into the ML-DE algorithm and propose a maximum likelihood-based adaptive differential evolution algorithm. The simulation study indicates the efficiency of the proposed algorithms.     

Exactly satisfying initial conditions neural network models for numerical treatment of first Painlevé equation

In this paper, novel computing approach using three different models of feed-forward artificial neural networks (ANNs) are presented for the solution of initial value problem (IVP) based on first Painlevé equation. These mathematical models of ANNs are developed in an unsupervised manner with capability to satisfy the initial conditions exactly using log-sigmoid, radial basis and tan-sigmoid transfer functions in hidden layers to approximate the solution of the problem. The training of design parameters in each model is performed with sequential quadratic programming technique. The accuracy, convergence and effectiveness of the proposed schemes are evaluated on the basis of the results of statistical analyses through sufficient large number of independent runs with different number of neurons in each model as well. The comparisons of these results of proposed schemes with standard numerical and analytical solutions validate the correctness of the design models.     

Control of the particle microstructure during the synthesis of bulk-polymerized transparent methacrylate-acrylonitrile-butadiene-styrene resin

A series of methacrylate-acrylonitrile-butadiene-styrene (MABS) resins was prepared using bulk polymerization. The polarity of the continuous phase and the compatibility of two phases were changed by adjusting the methyl methacrylate (MMA) content, choosing values that were close to styrene-butadiene rubber solubility value. The possibility of controlling the microstructure of the MABS resin by changing the polarity of the components and the compatibility of two phases was assessed. The dynamic mechanical analysis shows that the compatibility of two phases varies with the MMA content. The morphological analysis shows that increasing MMA contents results in a gradual decrease in the sub-inclusion structure with a network skeleton of rubber particles, and that all the particles become solid rubber when the MMA content reaches 75%. The sub-inclusion structure reappears but does not have a network skeleton when the MMA content is 90%. The impact strength and morphological analysis indicate that the solid rubber particles and the sub-inclusion structure with a network skeleton provide excellent toughness, while the sub-inclusion structure without a network skeleton does not. In contrast, the transmittance of the ABS resin first increased and then decreased with increasing MMA content.     

Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations

Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B₄ (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types.     

黑龙江省节水增粮行动(2012—2015年)实施方案

文章通过对黑龙江省高效节水现状,存在问题的分析,结合黑龙江省高效节水发展的支撑能力,阐述黑龙江省节水增粮目标、任务及总体布局,为黑龙江省2012—2015年节水增粮实施提供依据。     

高密度聚乙烯/丁苯橡胶热塑性硫化胶的形状记忆性能

采用动态硫化法制备了高密度聚乙烯(HDPE)/丁苯橡胶(SBR)热塑性硫化胶(TPV),研究了橡塑比、定型温度、回复温度及增容剂苯乙烯-丁二烯-苯乙烯嵌段共聚物(SBS)对HDPE/SBR TPV形状记忆性能的影响,观察了其微观结构,提出了形状记忆行为机制。结果表明,HDPE/SBR TPV具有典型的"海-岛"结构,拉伸后其表面存在明显的取向结构;SBS能显著提高HDPE/SBR TPV的形状记忆性能,当SBS用量为6份、定型温度和回复温度均为120℃时,HDPE/SBR TPV的形状记忆性能最佳。