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.     

Corrosion behaviors of carbon steel induced by life activities of Phaeodactylum tricornutum in a marine environment

Microbiologically influenced corrosion induced by bacteria has been studied for many years. Corrosion is known to be sensitive to the presence of microalgae, such as Phaeodactylum tricornutum. However, the life activity of P. tricornutum that influences the general and localized corrosion of carbon steel is not fully understood. The current study uses a combination of immersion tests and electrochemical experiments with a detailed surface characterization to reveal the naturally formed corrosion products with/without the presence of P. tricornutum. The results show that samples suffer from pitting corrosion and the averaged pit depths are approximately 15 μm under a light–dark cycle condition or a 24-h constant light condition. Meanwhile, the corrosion products are mainly comprised of γ-FeOOH and Fe₃O₄ in a constant light condition. However, γ-FeOOH, Fe₃O₄, and FeCO₃ are found in a light–dark cycle. This study proposes the fundamental mechanisms of the effect of P. tricornutum life activities on the corrosion performance of Q235 carbon steel, to fulfill the knowledge gaps of the presence of microalgae inducing the general and pitting corrosion of carbon steel.     

The surface carboxyl group of carbonaceous microspheres effects on the synthesis and structure of SiOC ceramics

In this study, C/SiOC and C/SiO₂ composites were prepared by using carbonaceous microspheres with different surface functional groups. Carbonaceous microspheres based on hydrothermal reaction of glucose contains hydroxyl group, while the surface carboxyl group increases after NaOH etching. The hydroxyl group increases the oxygen-enriched structural units of SiOC ceramics, and the C spheres are closely enwrapped in SiOC matrix after pyrolysis at 900 °C. However, the interfacial reaction of surface carboxyl with Si–OH results in the formation of cristobalite SiO₂, and C spheres are not only encased inside the SiOC matrix, but also dispersed outside of SiOC ceramics. After removal of C via calcination at 500 °C for 5 h, C/SiOC and C/SiO₂ composites are transformed into amorphous SiO₂ and cristobalite SiO₂, respectively. The thermogravimetric analysis indicates the oxidation resistance of SiOC is superior to that of C and SiO₂.     

Characteristics of Preferential Flow Paths in Reservoirs After Polymer Flooding and an Adaptive Compound Flooding Method

Chemistry and Technology of Fuels and Oils - When a reservoir is subjected to long-term water and polymer flooding, the formed preferential flow paths are widely distributed in the formation, and...     

基于带缺失PISA数据对中国学生科学素养的诊断分析

利用DINA模型(Deterministic inputs,noisy and gate model)对PISA2015中国学生科学素养数据进行建模,使用贝叶斯M CMC算法实现对缺失数据的自动填补和模型参数的估计.     

Highly oriented α-Al2O3 transparent ceramics shaped by shear force

Alumina platelets were arranged horizontally in submicron alumina particles by shear force in the flow of slurries during casting. The obtained alumina green bodies with platelets were pressureless-sintered in vacuum, producing ceramics with thoroughly oriented grains and high transmittance. The effects of sintering parameters on the densification, microstructure evolution, and orientation degree of alumina ceramics were investigated and discussed. The results showed that the densification, grain size, orientation degree, and in-line transmittance were increased with increasing sintering temperature. The enhancement of orientation degree was mainly coherent with grain growth. The grain-oriented samples exhibited a much higher in-line transmittance (at 600 nm) of 61 % than that of the grain random sample (29 %). Moreover, the transmission remained a high level in the ultraviolet range (<300 nm).     

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

Bi-templated grain growth maximizing the effects of texture on piezoelectricity

Templated grain growth is beneficial for piezoelectric materials, the properties of which become the best in their single crystalline form. Nevertheless, a textured ceramic prepared by a templated grain growth technique often fails in exhibiting as good properties as expected in single crystals even with a high degree of orientation factor. Here, we propose a new strategy for maximizing texturing effect by suppressing the growth of untextured matrix grains. The textured ceramics made by our method, so-called bi-templated grain growth, are featured by ultrahigh piezoelectric properties (d₃₃ = ～1,031 pC/N, d?g = ～59,000, k_p = ～0.76). A special emphasis is on the achieved electric-field-induced strain of 0.13 % at 1 kV/mm, which is as high as that of single crystals. This work demonstrates that not only the degree of texture but also the coarsening of untextured matrix grains should be well-controlled to best exploit the templated grain growth technique.     

Optimization of sensitizer concentration for upconversion photoluminescence of Yb3+/Er3+: La10W22O81 nanophosphor rods

Yb³⁺/Er³⁺codoped La₁₀W₂₂O₈₁ (LWO) nanophosphor rods have been successfully synthesized by a facile hydrothermal assisted solid state reaction method, and their upconversion photoluminescence properties were systematically studied. X-ray diffraction patterns revealed that the nanophosphors have an orthorhombic structure with space group Pbcn (60). A microflowers-like morphology with irregular hexagonal nanorods was observed using field emission scanning electron microscopy for the Yb³⁺(2 mol%)/Er³⁺(2 mol%):LWO nanophosphor. The shape and size of the nanophosphor and the elements along with their ionic states in the material were confirmed by TEM and XPS studies, respectively. A green upconversion emission was observed in the Er³⁺: LWO nanophosphors under 980 nm laser excitation. A significant improvement in upconversion emission has been observed in the Er³⁺: LWO nanophosphors by increasing the Er³⁺ ion concentration. A decrease in the upconversion emission occurred due to concentration quenching when the doping concentration of Er³⁺ ions was greater than 2 mol%. An optimized Er³⁺(2 mol%): LWO nanophosphor exhibited a strong near infrared emission at 1.53 μm by 980 nm excitation. The green upconversion emission of Er³⁺(2 mol%): LWO was remarkably enhanced by co-doping with Yb³⁺ ions under 980 nm excitation because of energy transfer from Yb³⁺ to Er³⁺. The naked eye observed this upconversion emission when co-doping with 2 mol% Yb³⁺. In order to obtain the high upconversion green emission, the optimized sensitizer concentration of Yb³⁺ ions was found to be 2 mol%. The upconversion emission trends were studied as a function of stimulating laser power for an optimized sample. Moreover, the NIR emission intensity has also been enhanced by co-doping with Yb³⁺ ions due to energy transfer from Yb³⁺ to Er³⁺. The energy transfer dynamics were systematically elucidated by energy level scheme. Colorimetric coordinates were determined for Er³⁺ and Yb³⁺/Er³⁺: LWO nanophosphors. The energy transfer mechanism was well explained and substantiated by several fluorescence dynamics of upconversion emission spectra and CIE coordinates. The results demonstrated that the co-doped Yb³⁺(2 mol%)/Er³⁺(2 mol%): LWO nanophosphor material is found to be a suitable candidate for the novel upconversion photonic devices.