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.     

微纳层叠聚丙烯腈凝胶流动特性的数值模拟研究

建立了层叠流道的三维模型和有限元网格模型，根据流变测试数据，采用Polymat对物料的黏度模型参数进行拟合，并利用Polyflow软件对聚丙烯腈（PAN）凝胶在层叠流道内的三维等温流动过程进行了数值模拟分析。研究发现，当入口流量增大时，层叠流道出口速度的不均匀性增加；沿流动方向流道内压力逐渐降低，并在出口处降低至同一最低值；流道进出口压力差与入口流量大小具有正相关性；在流道的中心截面上剪切速率分布均匀，波动较小。     

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.     

对“垃圾衍生燃料”RDF之探析

当前,我国水泥工业在可燃废弃物应用技术方面都还处于一家一户、自制自用、效率极低的初级阶段。发达国家的替代燃料:“垃圾衍生燃料”RDF、“固体回收燃料”SRF、“次煤”Subcoal和“纸塑垃圾衍生燃料”RPF制成的原材料都是可燃废弃物,只是处理工艺技术不同或者由垃圾中分拣出的可燃废弃物不同,制成颗粒状衍生燃料的品质不同,这些都可以替代部分甚或替代全部化石燃料在水泥窑炉中应用。我国大力发展“替代燃料”产业,有助于水泥工业消纳更多的“可燃废弃物”,为改善环境尤其是城镇环境和面貌,为我国的节能减排和绿色高质量发展发挥更大的作用。     

2.3–21 GHz broadband and high linearity distributed low noise amplifier

This paper focuses on the design of a 2.3–21 GHz Distributed Low Noise Amplifier (LNA) with low noise figure (NF), high gain (S₂₁), and high linearity (IIP3) for broadband applications. This distributed amplifier (DA) includes S/C/X/Ku/K-band, which makes it very suitable for heterodyne receivers. The proposed DA uses a 0.18 μm GaAs pHEMT process (OMMIC ED02AH) in cascade architecture with lines adaptation and equalization of phase velocity techniques, to absorb their parasitic capacitances into the gate and drain transmission lines in order to achieve wide bandwidth and to enhance gain and linearity. The proposed broadband DA achieved an excellent gain in the flatness of 13.5 ± 0.2 dB, a low noise figure of 3.44 ± 1.12 dB, and a small group delay variation of ±19.721 ps over the range of 2.3–21 GHz. The input and output reflection coefficients S₁₁ and S₂₂ are less than −10 dB. The input compression point (P_1dB) and input third-order intercept point (IIP3) are −1.5 dBm and 11.5 dBm, respectively at 13 GHz. The dissipated power is 282 mW and the core layout size is 2.2 × 0.8 mm².     

Effect of Fe2+ and Fe0 Applied Photo‐Fenton Processes on Sludge Disintegration

The disintegration of waste active sludge was investigated by photo‐Fenton processes. A batch study was conducted to evaluate parameters, such as Fe²⁺ and Fe⁰ ions and H₂O₂, governing the activated sludge integration by the photo‐Fenton process. Under optimum conditions, the concentration of soluble chemical oxygen demand (SCOD) with the classical Fenton process (CFP) increased very rapidly in the first five minutes due to the sufficient presence of reaction components in the medium, and then the rate of increase declined. In the modified Fenton process (FTP), the SCOD concentration increased more slowly as metallic iron powder must first be dissolved. The photo‐Fenton process proved to be a feasible and efficient process for the disintegration of waste sludge.     

生物质基喷气燃料的生产及应用进展

生物质基喷气燃料是指全部或大部分来源于生物资源的喷气燃料，符合清洁低碳、安全高效的现代能源体系的要求。以生物质基喷气燃料替代传统石油基喷气燃料有助于我国早日实现“碳达峰、碳中和”的远大目标。在阐述生物质基喷气燃料生产工艺的发展历程及生物质基喷气燃料应用现状的基础上，提出高密度的生物质基喷气燃料是未来喷气燃料的发展方向，具有多环结构的生物质是合成高密度生物质基喷气燃料组分的优质原料；同时，总结了高密度生物质基喷气燃料组分生产工艺的研究进展，展望了生物质基喷气燃料未来的发展及挑战。     

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.     

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.     

Photo isomerization of cis-cyclooctene to trans-cyclooctene: Integration of a micro-flow reactor and separation by specific adsorption

Liquid-phase adsorption has hardly been established in micro-flow, although this constitutes an industrially vital method for product separation. A micro-flow UV-photo isomerization process converts cis-cyclooctene partly into trans-cyclooctene, leaving an isomeric mixture. Trans-cyclooctene adsorption and thus separation was achieved in a fixed-bed micro-flow reactor, packed with AgNO₃/SiO₂ powder, while the cis-isomer stays in the flow. The closed-loop recycling-flow has been presented as systemic approach to enrich the trans-cyclooctene from its cis-isomer. In-flow adsorption in recycling-mode has hardly been reported so that a full theoretical study has been conducted. This insight is used to evaluate three process design options to reach an optimum yield of trans-cyclooctene. These differ firstly in the variation of the individual residence times in the reactor and separator, the additional process option of refreshing the adsorption column under use, and the periodicity of the recycle flow.