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 and slurry spray coating of barium strontium alumino silicate on SiC substrate

Barium strontium alumino silicate (BSAS); (Ba_0.6Sr_0.4Al₂Si₂O₈) was synthesized through solid state reaction between BaCO₃, SrCO₃, Al₂O₃ and SiO₂ subjected to wet milling in isopropanol for about 24 h. The sequence of the solid state reaction was studied by subjecting to DG/DTG from room temperature to 1550 °C. The crystallographic phase evolution was confirmed by X-ray diffraction of the powders calcined in the range 1000 to 1300 °C for 2 h. The monoclinic celsian phase obtained at 1300 °C, pelletized through uniaxial pressing was sinterable to 67 to 78% density in the temperature range of 1300 to 1500 °C. The density improved to 75 to 94% after ball milling for 76 h, while ZrO₂ addition further improved the density by 2%. The celcian phase of BSAS was dispersed in isopropyl alcohol, milled for about 24 h and spray coated on to plain SiC and mullite precoated SiC substrates. Sintering of coated samples and characterization for weight gain/loss, microstructure, scratch test prove that mullite + BSAS coating is more effective than single layer coating of BSAS on SiC substrates.     

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.     

杂化包覆玄武岩鳞片/环氧涂料制备与性能

本文在环氧涂料中添加玄武岩鳞片，提高其防腐蚀性能。针对玄武岩鳞片的团聚问题，通过机械力化学改性工艺，采用正硅酸四乙酯、HY-311型钛酸酯偶联剂、E-44型环氧树脂对玄武岩鳞片进行杂化包覆，结果表明，杂化包覆后玄武岩鳞片的沉降时间从2h提高至96 h。杂化包覆玄武岩鳞片添加量为20%涂层的性能最优，附着力为13.40 MPa，耐盐雾时间为2000 h，在3.5%NaCl溶液中浸泡2000 h后，0.01 Hz的阻抗模值仍然有5.15×109 Ω·cm2。     

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.     

Water vapor volatilization and oxidation induced surface cracking of environmental barrier coating systems: A numerical approach

A numerical model is developed for surface crack propagation in brittle ceramic coatings, aiming at the intrinsic failure of rare-earth silicate environmental barrier coating systems (EBCs) under combustion conditions in advanced gas turbines. The main features of progressive degradation of EBCs in such conditions are captured, including selective silica vaporization in the top coat due to exposure to water vapor, diffusion path-dependent bond coat oxidation, as well as crack propagation during cyclic thermal loading. In light of these features, user-defined subroutines are implemented in finite element analysis, where surface crack growth is simulated by node separation. Numerical results are validated by existing experimental data, in terms of monosilicate layer thickening, thermal oxide growth, and fracture behaviors. The experimentally observed quasi-linear oxidation in the early stage is also elucidated. Furthermore, it is suggested that surface crack undergoes rapid propagation in the late stage of extended thermal cycling in water vapor and leads to catastrophic failure, driven by both thermal mismatch and oxide growth stresses. The latter is identified as the dominant mechanism of penetration. Based on detailed analyses of failure mechanisms, the optimization strategy of EBCs composition is proposed, balancing the trade-off between mechanical compliance and erosion resistance.     

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.     

Inhibited intracrystalline cracks and enhanced electrochemical properties of NCM811 cathode materials coated by EPS

The formation of micro-cracks in Ni-rich LiNi_0.8Co_0.1Mn_0.1O₂ (NCM811) cathode particles is an extremely important factor affecting the electrochemical characteristics after long-term cycling. Generally, cracks can be divided into intergranular crack and intracrystalline crack according to their positions. Coating has been confirmed as a highly effective strategy to relieve intergranular cracks. However, the intracrystalline cracks of primary-like particles have rarely been studied. In this work, ethoxy functional polysiloxane (EPS) was directly coated on the surface of original NCM811 by tetraethyl orthosilicate (TEOS) hydrolytic polycondensation method without any additives. Then, the microstructure, micromorphology, surface state and electrochemical properties were investigated in detail by XRD, SEM, TEM, CV and EIS. The results displayed that the micro-cracks of primary-like particles were effectively suppressed under appropriate EPS coating. Accordingly, excellent capacity retention of 95.6% (100 cycles, 1C) and rate performance (144.6 mA h/g, 5C) were obtained. These improved mechanical and electrochemical properties are considered to be related to the EPS stress buffer layer, suppressed oxygen vacancies, inhibited phase transition and reduced volume change.     

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.