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. 相似文献
The presence of Mn(II) in water exceeding the permitted concentration limits declared by the World Health Organization (WHO) influences individuals, animals, and the ecosystem negatively. Therefore, there is a necessity for an efficient material to eliminate this potentially toxic element from wastewater. We herein focused on the adsorptive removal of Mn(II) ions from polluted aqueous media using natural Egyptian glauconite clay (G) and its nanocomposites with modified chitosan (CS). We applied modified chitosan with glutaraldehyde (GL), ethylenediaminetetraacetic acid (EDTA), sodium dodecyl sulfate (SDS), and cetyltrimethyl ammonium bromide (CTAB). The utilized nanocomposites were referred to as GL-CS/G, EDTA-GL-CS/G, SDS-CS/G, and CTAB-CS/G, respectively. The point of zero charge values of the materials were estimated. The adsorption properties of the G clay and its nanocomposites toward the removal of Mn(II) ions from polluted aqueous media as well as the adsorption mechanism were explored using a batch technique. The glauconite (G) and its nanocomposites: GL-CS/G, CTAB-CS/G, EDTA-GL-CS/G, and SDS-CS/G, exhibited maximum adsorption capacity values of 3.60, 24.0, 26.0, 27.0, and 27.9 mg g?1, respectively. The adsorption results fitted well the Langmuir isotherm and pseudo-second-order kinetic models. The estimated thermodynamic parameters: ΔH° (from 1.03 to 5.55 kJ/mol) and ΔG° (from ? 14.5 to ? 18.8 kJ/mol), indicated that Mn(II) ion adsorption process was endothermic, spontaneous, and physisorption controlled. Furthermore, the obtained adsorption results are encouraging and revealing a great potentiality for using the modified adsorbents as accessible adsorbents for Mn(II) ion removal from polluted aqueous solutions, depending on their reusability, high stability, and good adsorption capacities.
Catalysis Letters - We converted agro-waste Custard Apple Peels (CAP) to ash via thermal treatment, on which Pd(OAc)2 was immobilized easily that produced a low-cost, highly efficient Pd/CAP-ash... 相似文献
Nutrient Cycling in Agroecosystems - Reducing agriculturally derived diffuse contaminant losses (via non-point sources) from land to water has proven difficult for decades. Owing to the diversity... 相似文献
Polyamines are ubiquitous, low-molecular-weight aliphatic compounds, present in living organisms and essential for cell growth and differentiation. Copper amine oxidases (CuAOs) oxidize polyamines to aminoaldehydes releasing ammonium and hydrogen peroxide, which participates in the complex network of reactive oxygen species acting as signaling molecules involved in responses to biotic and abiotic stresses. CuAOs have been identified and characterized in different plant species, but the most extensive study on a CuAO gene family has been carried out in Arabidopsis thaliana. Growing attention has been devoted in the last years to the investigation of the CuAO expression pattern during development and in response to an array of stress and stress-related hormones, events in which recent studies have highlighted CuAOs to play a key role by modulation of a multilevel phenotypic plasticity expression. In this review, the attention will be focused on the involvement of different AtCuAOs in the IAA/JA/ABA signal transduction pathways which mediate stress-induced phenotypic plasticity events. 相似文献
Ce:Y3Al5O12 transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce3+ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)3(Al,Mn)5O12 TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb3+ and Mn2+ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb3+ ion and the energy transfer between Ce3+ and Mn2+ ions were verified in prepared TCs. 相似文献
Atomic Energy - The physical aspects and main results of reactor tests of a two-stage core consisting of fresh fuel assemblies and a significant number of fuel assemblies from the previous core,... 相似文献
Journal of Electronic Testing - Applications like Recognition, Mining, and Synthesis (RMS) with error-resilience properties can use circuits that produce acceptable results. In other words, the... 相似文献
Journal of Communications Technology and Electronics - An option of multicriteria collision risk ranking of aircraft by data from an onboard radar station (OBRS) is proposed. This method can be... 相似文献
Barium strontium alumino silicate (BSAS); (Ba0.6Sr0.4Al2Si2O8) 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. 相似文献