Composition Design and Fundamental Properties of Ultra-High-Performance Concrete Based on a Modified Fuller Distribution Model.

Both the discrete and continuous particle packing models are used to design UHPC, but the influences of a water film covering the particle surfaces on the compactness of the particle system were not considered in these models. In fact, the water film results in a certain distance between solid particles (DSP), which affects the compactness of the particle system, especially for cementitious materials with small particle sizes. In the present study, the mixture design method for UHPC was proposed based on the Fuller distribution model modified using the DSP. Then, the components of cementitious materials and aggregates were optimized, and the UHPC matrices with high solid concentrations were obtained. The results showed that the solid concentration, slump flow, and compressive strength of the UHPC matrix reached 77.1 vol.%, 810 mm, and 162.0 MPa, respectively. By replacing granulated blast furnace slag (GBFS) with quartz powder (QP), the flexural strength of the UHPC matrix was increased without reducing its compressive strength. When the steel fiber with a volume fraction of 1.5% was used, the slump flow, compressive strength, tensile strength, and flexural strength of the UHPC reached 740 mm, 175.6 MPa, 9.7 MPa, and 22.8 MPa, respectively. After 500 freeze-thaw cycles or 60 dry-wet cycles under sulfate erosion, the mechanical properties did not deteriorate. The chloride diffusion coefficients in UHPCs were lower than 3.0 × 10-14 m2/s, and the carbonation depth of each UHPC was 0 mm after carbonization for 28 days. The UHPCs presented ideal workability, mechanical properties, and durability, demonstrating the validity of the method proposed for UHPC design.

Oct4A palmitoylation modulates tumorigenicity and stemness in human glioblastoma cells.

BACKGROUND: Glioblastoma multiforme and other solid malignancies are heterogeneous, containing subpopulations of tumor cells that exhibit stem characteristics. Oct4, also known as POU5F1, is a key transcription factor in the self-renewal, proliferation, and differentiation of stem cells. Although it has been detected in advanced gliomas, the biological function of Oct4, and transcriptional machinery maintained by the stemness of Oct4 protein-mediated glioma stem cells (GSC), has not been fully determined. METHODS: The expression of Oct4 variants was evaluated in brain cancer cell lines, and in brain tumor tissues, by quantitative real-time PCR, western blotting, and immunohistochemical analysis. The palmitoylation level of Oct4A was determined by the acyl-biotin exchange method, and the effects of palmitoylation Oct4A on GSCs were investigated by a series of in vitro (neuro-sphere formation assay, double immunofluorescence, pharmacological treatment, luciferase assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments. RESULTS: Here, we report that all three variants of Oct4 are expressed in different types of cerebral cancer, while Oct4A is important for maintaining tumorigenicity in GSCs. Palmitoylation mediated by ZDHHC17 was indispensable for preserving Oct4A from lysosome degradation to maintain its protein stability. Oct4A palmitoylation also helped to integrate Sox4 and Oct4A in the SOX2 enhancement subregion to maintain the stem performance of GSCs. We also designed Oct4A palmitoylation competitive inhibitors, inhibiting the self-renewal ability and tumorigenicity of GSCs. CONCLUSIONS: These findings indicate that Oct4A acts on the tumorigenic activity of glioblastoma, and Oct4A palmitoylation is a candidate therapeutic target.

GSK3ß palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2-STAT3 axis.

Glioblastoma stem cells (GSCs) are a highly tumorigenic cell subgroup of glioblastoma (GBM). Glycogen synthase kinase 3ß (GSK3ß) is considered a key hub for promoting malignant phenotypes in GBM. However, the functional relationships between GSK3ß and GSCs in GBM are unclear. Here, we found that GSK3ß was noted as a substrate for ZDHHC4-mediated palmitoylation at the Cys14 residue, which enhanced GBM temozolomide (TMZ) resistance and GSC self-renewal. Clinically, the expression level of ZDHHC4 was upregulated in GBM, which significantly correlated with tumor grade and poor prognosis. The above phenotypes were based on decreasing p-Ser9 and increasing p-Tyr216 by GSK3ß palmitoylation, which further activated the enhancer of the zeste homolog 2 (EZH2)-STAT3 pathway. Notably, STAT3 silencing also inhibited ZDHHC4 expression. This study revealed that GSK3ß palmitoylation mediated by ZDHHC4 improved the stemness of TMZ-resistant GBM by activating the EZH2-STAT3 signaling axis, providing a new theoretical basis for further understanding the mechanism of TMZ resistance and recurrence after treatment.

SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage.

PURPOSE: The prevalence of epidermal growth factor receptor (EGFR) mutations in glioblastoma multiforme (GBM) has elicited a significant focus on EGFR as a potential drug target. However, no significant clinical advancement in GBM treatment has occurred. METHODS AND MATERIALS: Bioinformatics analysis, western blotting, immunofluorescence, and immunohistochemistry were performed to detect the expression of ZDHHC16 and genetic EGFR alterations in GBM. The biological function of ZDHHC16/SETD2/H3K36me3 signaling axis after EGFR alterations was demonstrated by various in vitro (pharmacologic treatment, flow cytometry, transwell migration assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments. RESULTS: We demonstrate that the ZDHHC16/SETD2/H3K36me3 signaling axis was inactivated in EGFR-altered GBM. ZDHHC16 was downregulated in GBM versus normal brain tissue; this was significantly related to EGFR alterations. These events contributed to p53 activation, halting cells at the G1/S checkpoint. Furthermore, DNA damage repair signaling in EGFR-amplified GBMs was affected after ionizing radiation-induced DNA damage via reduced SETD2 palmitoylation and methylation of its target, H3K36. Our findings suggest that a depalmitoylation inhibitor, PalmB, is useful as a potentially novel adjuvant treatment for patients with GBM undergoing radiation therapy. CONCLUSIONS: Our data present novel mechanistic evidence relating to signaling pathways with DNA damage responses in EGFR-mutated GBM.

Optimization of coating uniformity in a simple rotation system by using a rotating shadow mask.

A theoretically designed rotating shadow mask is proposed to optimize the uniformity of a simple rotation system, which makes full use of the width of the coating chamber. This method can fabricate a large-aperture optical component, the diameter of which is more than half the width of the coating machine. The rotating shadow mask is applied to correct the film thickness uniformity near the center point of simple plane substrate. The factors influencing the effect of the rotating shadow mask are simulated and discussed. Then the shape of the rotating shadow mask is theoretically designed, and the uniformity within a corresponding radius is well corrected. After determining the shape of the rotating shadow mask, an additional fixed shadow mask is calculated and used to improve the uniformity of the entire substrate. Through the application of the two shadow masks together, uniformity about 99.5% is obtained in the diameter of 640 mm on a 1100 mm coating machine.

Application of the J-Integral and Digital Image Correlation (DIC) to Determination of Multiple Crack Propagation Law of UHPC under Flexural Cyclic Loading.

This study investigated the fatigue crack propagation behavior of ultra-high-performance concrete (UHPC) incorporated with different steel fiber lengths of 6, 13, and 20 mm under flexural cyclic loading, based on the Paris law and nonlinear fracture mechanics. In addition, multiple crack covering areas and fatigue J-integral amplitudes were employed to quantitatively evaluate the fatigue crack propagation rate and predicate the fatigue life of the UHPC during the steady development stage. The results indicated that the maximum crack opening displacement (COD) values were 0.312, 0.673, and 1.265 mm and the minimum crack growth rates were -3.05, -4.48 and -4.62 for SF6, SF13, and SF20, respectively. The critical crack length was approximately 65 mm for UHPC specimens containing different fiber length at a given fiber volume fraction (2.0%), indicating that the critical crack length was simply related to the fiber length. Interestingly, when the fatigue crack area of all the tested series reached approximately 35 mm2, fracture failure occurred. There were very small predictions between the actual tested and predicated fatigue lives, all less than 7.21%. Hence, it was reasonable to predict the fatigue life of the UHPC based on the J-integral according to the DIC technique.

Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation.

Glioblastoma (GBM) is the most common and deadly of the primary intracranial tumors and is comprised of subsets that show plasticity and marked heterogeneity, contributing to the lack of success in genomic profiling to guide development of precision medicine for these tumors. In this study, a mutation in isocitrate dehydrogenase 1 was found to suppress the transforming growth factor-beta signaling pathway and E2F4 interacted with Smad3 to inhibit expression of mesenchymal markers. However, palmitoylation of Smad3 mediated by palmitoyltransferase ZDHHC19 promoted activation of the transforming growth factor-beta signaling pathway, and its interaction with EP300 promoted expression of mesenchymal markers in the mesenchymal subtype of GBM. Smad3 and hypoxia-inducible factor 1-alpha may be important molecular targets for treatment of glioma because they appear to coordinate the basic aspects of cancer stem cell biology.

CuInS2 quantum dot-sensitized TiO2 nanorod array photoelectrodes: synthesis and performance optimization.

CuInS2 quantum dots (QDs) were deposited onto TiO2 nanorod arrays for different cycles by using successive ionic layer adsorption and reaction (SILAR) method. The effect of SILAR cycles on the light absorption and photoelectrochemical properties of the sensitized photoelectrodes was studied. With optimization of CuInS2 SILAR cycles and introduction of In2S3 buffer layer, quantum dot-sensitized solar cells assembled with 3-µm thick TiO2 nanorod film exhibited a short-circuit current density (Isc) of 4.51 mA cm-2, an open-circuit voltage (Voc) of 0.56 V, a fill factor (FF) of 0.41, and a power conversion efficiency (η) of 1.06%, respectively. This study indicates that SILAR process is a very promising strategy for preparing directly anchored semiconductor QDs on TiO2 nanorod surface in a straightforward but controllable way without any complicated fabrication procedures and introduction of a linker molecule.

One-step synthesis of stoichiometric Cu2ZnSnSe4 as counter electrode for dye-sensitized solar cells.

Cu(2)ZnSnSe(4) (CZTSe) nanoparticles with diameters of 200-300 nm were synthesized by one-step solvothermal method without surfactants or templates. The structure, composition and morphology of CZTSe nanoparticles were characterized by XRD, XPS, Raman spectrum, EDS, FESEM and TEM. The results indicated that the nanoparticles were single phase and nearly stoichiometric composition. CZTSe nanoparticles drop-casted onto FTO substrate were used as counter electrode (CE) in dye-sensitized solar cells (DSSCs) for the first time, which exhibited Pt-like electrocatalytic activity for the reduction of I(3)(-) to I(-) in DSSCs. The J-V results demonstrated that the thickness of the film affected the photocurrent density and fill factor remarkably, which resulted from the difference of electrocatalytic sites and resistance with different thickness films. And a best efficiency of 3.85% was obtained by adjusting the film thickness. The work presents a new approach for developing low-cost, facile fabrication CZTSe nanoparticles, and demonstrates CZTSe can be explored as a low-cost alternative for expensive and scare Pt in DSSCs.

Effect of highly ordered single-crystalline TiO2 nanowire length on the photovoltaic performance of dye-sensitized solar cells.

One-dimensional semiconductor nanostructures grown directly onto transparent conducting oxide substrates with a high internal surface area are most desirable for high-efficiency dye-sensitized solar cells (DSSCs). Herein, we present a multicycle hydrothermal synthesis process to produce vertically aligned, single crystal rutile TiO(2) nanowires with different lengths between 1 and 8 µm for application as the working electrode in DSSCs. Optimum performance was obtained with a TiO(2) nanowire length of 2.0 µm, which may be ascribed to a smaller nanowire diameter with a high internal surface area and better optical transmittance with an increase in the incident light intensity on the N719 dye; as well as a firm connection at the FTO/TiO(2) nanowire interface.

Solution fabrication and photoelectrical properties of CuInS2 nanocrystals on TiO2 nanorod array.

One-dimensional semiconductor architectures are receiving attention in preparing photovoltaic solar cells because of its superior charge transport as well as excellent light-harvesting efficiency. In this study, vertically aligned single-crystalline TiO(2) nanorods array was grown directly on transparent conductive glass (FTO), and then CuInS(2) nanocrystals were deposited on nanorods array by spin coating method to form TiO(2)/CuInS(2) heterostructure films. The resulting nanostructure assembly and composition was confirmed by field-emission scanning electron microscope (FESEM) , transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction(XRD). Ultraviolet-visible absorption spectroscopy (UV-vis) data indicates that the absorbance of the nanocomposite film extended into the visible region compared with bare TiO(2) nanorod arrays. The surface photovoltage spectra (SPS) also showed a new and enhanced response region corresponding to the absorption spectrum. These results suggest that the novel CuInS(2) nanocrystals sensitized TiO(2) nanorod array on FTO photoelectrodes has a potential application in photovoltaic devices.