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.     

Mechanical properties and wear behavior of Tin+1(Al,A)Cn (A = Ga,In, Sn,n = 1, 2) via quasi-high-entropy of single atomic thick A layer

The strengthening method of multi-element M-site solid solution is a common approach to improve mechanical properties of MAX phase ceramic. However, the research on capability of multi-element A-site solid solution to improve mechanical properties has rarely been reported. Thereupon, quasi-high-entropy MAX phase ceramic bulks of Ti₂(Al_1?xA_x)C and Ti₃(Al_1?xA_x)C₂ (A = Ga, In, Sn, x = 0.2, 0.3, 0.4) were successfully synthesized by in situ vacuum hot pressing via multi-elements solid solution. The multi-elements solid solution in single-atom thick A layer was confirmed by X-ray diffraction and X-ray photoelectron spectroscopy as well as by energy dispersive X-ray spectroscopy mappings. Effects of doped multi-elements contents on the phase, microstructure, mechanical properties, and high temperature tribological behaviors were studied. Results demonstrated that the Vickers hardness, anisotropic flexural strength, fracture toughness, and tribological properties of Ti–Al–C based MAX ceramics could be remarkably improved by constitution of quasi-high-entropy MAX phase in A layers. Moreover, the strengthening and wear mechanisms were also discussed in detail. This method of multi-element solid solution at A-site provides new way to enhance mechanical properties of other MAX phase ceramics.     

Thermal desorption and pyrolysis direct analysis in real time mass spectrometry of Nafion membrane

Perfluorosulfonic acid ionomer membranes have been widely used as proton conducting membranes in various electrochemical processes such as polymer electrolyte fuel cells and water electrolysis. While their thermal stability has been studied by thermogravimetry and analysis of low molecular weight products, their decomposition mechanism is little understood. In this study a newly developed methodology of thermal desorption and pyrolysis in combination with direct analysis in real time mass spectrometry is applied for Nafion membrane. An ambient ionization source and a high-resolution time-of-flight mass spectrometer enabled unambiguous assignment of gaseous products. Thermal decomposition is initiated by side chain detachment above 350°C, which leaves carbonyls on the main chain at the locations of the side chains. Perfluoroalkanes are released above 400°C by main chain scission and their further decomposition products dominate above 500 °C. DFT calculation of reaction energies and barrier heights of model compounds support proposed decomposition reactions.     

Microstructural and mechanical properties assessment of transient liquid phase bonding of CoCuFeMnNi high entropy alloy

The transient liquid phase (TLP) bonding of CoCuFeMnNi high entropy alloy (HEA) was studied. The TLP bonding was performed using AWS BNi-2 interlayer at 1050 °C with the TLP bonding time of 20, 60, 180 and 240 min. The effect of bonding time on the joint microstructure was characterized by SEM and EDS. Microstructural results confirmed that complete isothermal solidification occurred approximately at 240 min of bonding time. For samples bonded at 20, 60 and 180 min, athermal solidification zone was formed in the bonding area which included Cr-rich boride and Mn₃Si intermetallic compound. For all samples, the γ solid solution was formed in the isothermal solidification zone of the bonding zone. To evaluate the effect of TLP bonding time on mechanical properties of joints, the shear strength and micro-hardness of joints were measured. The results indicated a decrement of micro-hardness in the bonding zone and an increment of micro-hardness in the adjacent zone of joints. The minimum and maximum values of shear strength were 100 and 180 MPa for joints with the bonding time of 20 and 240 min, respectively.     

一种植物油中苯并（a）芘含量测定的固相萃取前处理方法

为了建立一种准确性高、成本低的植物油中苯并(a)芘测定的样品前处理方法，基于GB 5009.7—2016以自制氧化铝柱为固相萃取柱，采用单因素试验对称样量、洗脱剂量、洗脱流速、吸附剂存放时间、吸附剂量这5个影响植物油中苯并（a）芘洗脱的因素进行研究，优化前处理条件，并对测定方法进行考察。结果表明：优化的前处理条件为称样量0.100 0 g、洗脱剂量120 mL、吸附剂（氧化铝）量22 g、洗脱流速1滴/2 s、吸附剂存放时间少于12周；方法检出限为0.2 μg/L，样品加标回收率为94.23%～100.00%，RSD为1.20%～7.36%；同一样品测定结果与SGS测定值接近，相对平均偏差为2.36%～3.50%。说明本试验方法测定结果准确，可应用于油脂企业植物油中痕量苯并（a）芘的测定。     

氮含量及固溶温度对21-6-9奥氏体不锈钢组织和硬度的影响

为了探讨氮含量及固溶温度对21-6-9不锈钢组织和硬度的影响,分别在950、1000、1050和1100 ℃对3种不同氮含量的热轧态21-6-9不锈钢进行1 h固溶处理,通过光学显微镜观察其组织结构,结合Thermo-Calc热力学计算对试验钢的微观组织进行分析,并对其进行硬度测试。结果表明,0.20%~0.28%N的21-6-9不锈钢热轧后沿轧制方向析出铁素体,且钢中铁素体经950~1100 ℃固溶处理可消除,当N含量达到0.34%时,试验钢中不再出现铁素体。随着固溶处理温度的升高,21-6-9不锈钢的晶粒组织长大,硬度降低。N含量的增加可显著提高固溶态21-6-9不锈钢的硬度,其增加程度随固溶处理温度的升高而减弱。     

An integrated dimensionality reduction and surrogate optimization approach for plant-wide chemical process operation

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems.     

Mg-bearing quartz solid solutions as structural intermediates between low and high quartz

Glass powder samples of cordierite composition (doped with 8 mol% TiO₂) were heat-treated to produce a series of increasingly SiO₂-enriched Mg-bearing quartz solid solutions (Qss). The obtained materials were then analyzed by X-ray diffraction: Rietveld structural refinements revealed that Mg-bearing Qss phases possess trigonal symmetry and a compositionally dependent intermediate structural arrangement between those of low and high quartz. High-temperature diffraction measurements were performed up to 700°C to characterize the thermal expansion behavior of the crystals. At SiO₂-rich compositions, a reversible high-to-intermediate inversion of the quartz structure is observed, which shifts with increasing stuffing to lower temperatures than the conventional 573°C for pure quartz. Similarities and differences to the better-established Li-bearing Qss are discussed in the text.     

In Silico Investigation of Potential Applications of Gamma Carbonic Anhydrases as Catalysts of CO2 Biomineralization Processes: A Visit to the Thermophilic Bacteria Persephonella hydrogeniphila,Persephonella marina,Thermosulfidibacter takaii,and Thermus thermophilus

Carbonic anhydrases (CAs) have been identified as ideal catalysts for CO₂ sequestration. Here, we report the sequence and structural analyses as well as the molecular dynamics (MD) simulations of four γ-CAs from thermophilic bacteria. Three of these, Persephonella marina, Persephonella hydrogeniphila, and Thermosulfidibacter takaii originate from hydrothermal vents and one, Thermus thermophilus HB8, from hot springs. Protein sequences were retrieved and aligned with previously characterized γ-CAs, revealing differences in the catalytic pocket residues. Further analysis of the structures following homology modeling revealed a hydrophobic patch in the catalytic pocket, presumed important for CO₂ binding. Monitoring of proton shuttling residue His69 (P. marina γ-CA numbering) during MD simulations of P. hydrogeniphila and P. marina’s γ-CAs (γ-PhCA and γ-PmCA), showed a different behavior to that observed in the γ-CA of Escherichia coli, which periodically coordinates Zn²⁺. This work also involved the search for hotspot residues that contribute to interface stability. Some of these residues were further identified as key in protein communication via betweenness centrality metric of dynamic residue network analysis. T. takaii’s γ-CA showed marginally lower thermostability compared to the other three γ-CA proteins with an increase in conformations visited at high temperatures being observed. Hydrogen bond analysis revealed important interactions, some unique and others common in all γ-CAs, which contribute to interface formation and thermostability. The seemingly thermostable γ-CA from T. thermophilus strangely showed increased unsynchronized residue motions at 423 K. γ-PhCA and γ-PmCA were, however, preliminarily considered suitable as prospective thermostable CO₂ sequestration agents.     

肇庆市固体废物产业发展方向探索

本文以肇庆市固体废物产业发展为实例,阐明全市固体废物产业发展现状以及发展方向,并提出了相应的策略。