Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

高稳高效海上风电安装平台关键制造技术研究

海上风电作为可再生清洁能源之一,受到世界各国的高度重视与大力发展。我国将海上风电提升至解决能源危机、减缓气候变化、调整能源结构的国家战略高度,到2030年我国单位国内生产总值二氧化碳排放将比2005年下降65%以上,非化石能源占一次能源消费比重将达到25%左右。安装平台不足将是我国海上风电场无法如期建成投产的主要障碍。对自升自航式海上风电安装平台系列高端装备及其设计制造的三大技术难题——腿站立作业易“失稳”、大平台大跨距大倾覆力矩自升易“失控”、高空吊装巨型叶片逾百螺栓精准定位易“失准”,以及焊缝缺陷修复和局部裂纹损伤的激光锻造修复再制造进行了介绍,研制的具有不同规格的系列装备在中国、英国、丹麦、德国等国家的著名海上风电场建设应用情况良好。     

Synthesis of thermoresponsive copolymer/silica-coated magnetite nanoparticle composite and its application for heavy metal ion recovery

To enhance chemical stability and suppress of aggregation of magnetite nanoparticles (MNPs), which are used as a support for thermoresponsive copolymer immobilization, silica coating of the MNPs is applied via the electrooxidation method. Although the resulting silica coated-MNPs also formed aggregates, the size distribution of the aggregate shifted to smaller size range. Because of that, the surface area available for copolymer immobilization increased approximately 6.7 times at maximum as compared with that of the uncoated MNPs. It contributed to the increase of the amount of the immobilized copolymer on the silica-coated MNPs, which is approximately four times larger than that on the uncoated MNPs. Fe₃O₄ dissolution test confirmed enhancement of chemical stability of MNPs. The thermoresponsive copolymer immobilized on the silica-coated MNPs shows the ability to recycle Cu(II) ion from Cu(II) containing solution by changing temperature with significantly shorter time than those in other thermoresponsive adsorbents in gel form.     

Achieving fabrication of highly transparent Y2O3 ceramics via air pre-sintering by deionization treatment of suspension

An easy albeit quite effective deionization suspension treatment was adopted to alleviate the detrimental effects related to the hydrolysis of Y₂O₃ in an aqueous medium. Fabrication of highly transparent Y₂O₃ ceramics with a fine grain size via air pre-sintering and post–hot isostatic pressing (HIP) treatment without using any sintering additive was achieved using the treated suspensions. The hydrolysis issue of Y₂O₃ powder in an aqueous medium was effectively alleviated by using deionization treatment, and a well-dispersed suspension with a low concentration of dissolved Y³⁺ species was obtained. The dispersed suspensions were consolidated by the centrifugal casting method, and the green bodies derived from the suspension of 35.0 vol% solid loading showed an improved homogeneity with a relative density of 52.1%. Fully dense Y₂O₃ transparent ceramic with high transparency was obtained by pre-sintering consolidated green compacts at a low temperature of 1400°C for 16 h in air followed by a post-HIP treatment at 1550°C for 2 h under 200 MPa pressure. The sample had a fine average grain size of 690 nm. The in-line transmittance of the sample reached 83.3% and 81.8% at 1100 nm and 800 nm, respectively, very close to the theoretical values of Y₂O₃.     

Nanolayer CrAlN/TiSiN coating designed for tribological applications

With the goal to produce a hard and tough coating intended for tribological applications, CrAlN/TiSiN nanolayer coating was prepared by alternative deposition of CrAlN and TiSiN layers. In the first part of the article, a detailed study of phase composition, microstructure, and layer structure of CrAlN/TiSiN coating is presented. In the second part, its mechanical properties, fracture and tribological behavior are compared to the nanocomposite TiSiN coating. An industrial magnetron sputtering unit was used for coating deposition. X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used for compositional and microstructural analysis. Mechanical properties and fracture behavior were studied by instrumented indentation and focused ion beam techniques. Tribological properties were evaluated by ball-on-disk test in a linear reciprocal mode. A complex layer structure was found in the nanolayer coating. The TiSiN layers were epitaxially stabilized inside the coating which led to formation of dislocations at interfaces, to introduction of disturbances in the coating growth, and as a result, to development of fine-grained columnar microstructure. Indentation load required for the onset of fracture was twice lower for the nanolayer CrAlN/TiSiN, compared to the nanocomposite TiSiN coating. This agrees very well with their mechanical properties, with H³/E² being twice higher for the TiSiN coating. However, the nanolayer coating experienced less severe damage, which had a strong impact on tribological behavior. A magnitude of order lower wear rate and four times lower steady state friction coefficient were found for the nanolayer coating.     

State-of-the-art technology: Recent investigations on laser-mediated synthesis of nanocomposites for environmental remediation

In both developing and industrialized/developed countries, various hazardous/toxic environmental pollutants are entering water bodies from organic and inorganic compounds (heavy metals and specifically dyes). The global population is growing whereas the accessibility of clean, potable and safe drinking water is decreasing, leading to world deterioration in human health and limitation of agricultural and/or economic development. Treatment of water/wastewater (mainly industrial water) via catalytic reduction/degradation of environmental pollutants is extremely critical and is a major concern/issue for public health. Light and/or laser ablation induced photocatalytic processes have attracted much attention during recent years for water treatment due to their good (photo)catalytic efficiencies in the reduction/degradation of organic/inorganic pollutants. Pulsed laser ablation (PLA) is a rather novel catalyst fabrication approach for the generation of nanostructures with special morphologies (nanoparticles (NPs), nanocrystals, nanocomposites, nanowires, etc.) and different compositions (metals, alloys, oxides, core-shell, etc.). Laser ablation in liquid (LAL) is generally considered a quickly growing approach for the synthesis and modification of nanomaterials for practical applications in diverse fields. LAL-synthesized nanomaterials have been identified as attractive nanocatalysts or valuable photocatalysts in (photo)catalytic reduction/degradation reactions. In this review, the laser ablation/irradiation strategies based on LAL are systematically described and the applications of LAL synthesized metal/metal oxide nanocatalysts with highly controlled nanostructures in the degradation/reduction of organic/inorganic water pollutants are highlighted along with their degradation/reduction mechanisms.     

Synthesis of succinic acid-based polyamide through direct solid-state polymerization method: Avoiding cyclization of succinic acid

Succinic acid is an important synthetic monomer but it is difficult to use it as a precursor for synthesizing high molecular weight polyamide, due to its tendency to perform intra-cyclization reaction at high temperature. In order to solve this problem, in this paper, the direct solid-state polymerization (DSSP) method with the initial reactant, nylon salt which was composed of 1, 5-diaminopentane, succinic acid, and terephthalic acid, was applied to synthesize the bio-based copolyamide PA 5T/54. In comparison with the conventional melting polymerization method, the DSSP method can prevent the cyclization reaction of succinic acid effectively due to the lower reacting temperature as well as the restriction effect of the nylon salt. As a result, the product fabricated by DSSP method has higher molecular weight and much lighter color from red to white. Therefore, the DSSP method is advantageous for the synthesis of the polymers or copolymers composed of the succinic acid as the monomer. Furthermore, the polymerization mechanism proposed in this work can serve as a guidance for the design of the molecular structure and control of the polymerization process.     

Phase,domain, and microstructures in Sr2+ substituted low-temperature sintering PZT-based relaxor ferroelectrics

The Ag-Pd internal electrode of multilayer piezoelectric ceramics needs to be sintered below 1000°C, and lead wires and components need to be welded with lead-free solder at 260°C. PNN–PMW–PZT–xSr piezoelectric ceramics with high Curie temperature (T_c > 260°C) were synthesized at a low sintering temperature (960°C) to meet the requirements of multilayer piezoelectric devices. The relationship between structures (phase, domain, and microstructures) and electrical properties (piezo/ferroelectric properties, and dielectric relaxation) in the Sr²⁺ substituted ceramics was investigated. Rietveld refinement and Raman spectra show that Sr²⁺ substitution can cause the phase change and increase the force constant of [BO₆] octahedron. The piezoelectric response increases with increasing the content of the tetragonal phase (CTP) in the rhombohedral-tetragonal (R-T) coexisted ceramics. The ceramics with 0.6 mol% Sr²⁺ substitution have minimum activation energy for domain wall movement (E_a) of 0.0362 eV which favors the formation of nanometer-sized domains, and possess excellent electrical properties (d₃₃ = 623 pC/N, d₃₃^* =783 pm/V, T_c =295°C). The higher the CTP, the lower the E_a. The lower E_a favors the rotation of polarization direction and extension, and is beneficial to the generation of the nanometer-size domains, resulting in high piezoelectric properties.     

Stress field and damage evolution in C/SiC woven composites: Image-based finite element analysis and in situ X-ray computed tomography tests

The construction and examination of meso-structural finite element models of a Chemical-Vapor-Infiltrated (CVI) C/SiC composite is carried out based on X-ray microtomography digital images (IB-FEM). The accurate meso-structural features of the C/SiC composites, which are consisted of carbon fiber tows and CVI-SiC matrix, in particular the cavity defects, are reconstructed. With the IB-FEM, the damage evolution and fracture behaviors of the C/SiC composite are investigated. At the same time, an in situ tensile test is applied to the C/SiC composite under a CT real-time quantitative imaging system, aiming to investigate the damage and failure features of the material as well as to verify the IB-FEM. The IB-FEM results indicate that material damage initially occur at the defects, followed by propagating toward the fiber-tow/SiC-matrix interfaces, ultimately, combined into macro-cracks, which is in good agreement with the in situ CT experiment results.     

Nano fibrillated cellulose-based foam by Pickering emulsion: Preparation,characterizations, and application as dye adsorbent

An ecofriendly and biodegradable porous structure was prepared from drying aqueous foams based on nano fibrillated cellulose (NFC), extracted from softwood pulp by subcritical water/CO₂ treatment (SC-NFC). The primary aim of this work was to use the modified SC-NFC as stabilizer for a water-based Pickering emulsion which upon drying, yielded porous cellulosic materials, a good dye adsorbent. In order to exploit the carboxymethylated SC-NFC (CMSC-NFC, with a degree of substitution of 0.35 and a charge density of 649 μeqv/g) as a stabilizer for water-based Pickering emulsion in subsequent step, an optimized quantity of octyl amine (30 mg/g of SC-NFC) was added to make them partially hydrophobic. A series of dry foam structures were prepared by varying the concentrations of treated CMSC-NFCs and 4 wt% was found to be the optimum concentration to yield foam with high porosity (99%) and low density (0.038 g/cc) along with high compression strength (0.24 MPa), superior to the conventionally extracted NFC. The foams were applied to capture as high as 98% of methylene blue dyes, making them a potential green candidate for treating industrial effluent. In addition, the dye adsorption kinetics and isotherms were found to be well suited with second order kinetics and Langmuir isotherm models.