114 research outputs found
Chromium removal from aqueous solution by a PEI-silica nanocomposite
It is essential and important to determine the adsorption mechanism as well as removal efficiency when using an adsorption technique to remove toxic heavy metals from wastewater. In this research, the removal efficiency and mechanism of chromium removal by a silica-based nanoparticle were investigated. A PEI-silica nanoparticle was synthesized by a one-pot technique and exhibited uniformly well-dispersed PEI polymers in silica particles. The adsorption capacity of chromium ions was determined by a batch adsorption test, with the PEI-silica nanoparticle having a value of 183.7 mg/g and monolayer sorption. Adsorption of chromium ions was affected by the solution pH and altered the nanoparticle surface chemically. First principles calculations of the adsorption energies for the relevant adsorption configurations and XPS peaks of Cr and N showed that Cr(VI), [HCrO4](-) is reduced to two species, Cr(III), CrOH2+ and Cr3+, by an amine group and that Cr(III) and Cr(VI) ions are adsorbed on different functional groups, oxidized N and NH3+
Structure-guided optimisation of N-hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-α
The human 2-oxoglutarate (2OG)- and Fe(II)-dependent oxygenases factor inhibiting hypoxia-inducible factor-α (FIH) and HIF-α prolyl residue hydroxylases 1–3 (PHD1–3) regulate the response to hypoxia in humans via catalysing hydroxylation of the α-subunits of the hypoxia-inducible factors (HIFs). Small-molecule PHD inhibitors are used for anaemia treatment; by contrast, few selective inhibitors of FIH have been reported, despite their potential to regulate the hypoxic response, either alone or in combination with PHD inhibition. We report molecular, biophysical, and cellular evidence that the N-hydroxythiazole scaffold, reported to inhibit PHD2, is a useful broad spectrum 2OG oxygenase inhibitor scaffold, the inhibition potential of which can be tuned to achieve selective FIH inhibition. Structure-guided optimisation resulted in the discovery of N-hydroxythiazole derivatives that manifest substantially improved selectivity for FIH inhibition over PHD2 and other 2OG oxygenases, including Jumonji-C domain-containing protein 5 (∼25-fold), aspartate/asparagine-β-hydroxylase (>100-fold) and histone Nε-lysine demethylase 4A (>300-fold). The optimised N-hydroxythiazole-based FIH inhibitors modulate the expression of FIH-dependent HIF target genes and, consistent with reports that FIH regulates cellular metabolism, suppressed lipid accumulation in adipocytes. Crystallographic studies reveal that the N-hydroxythiazole derivatives compete with both 2OG and the substrate for binding to the FIH active site. Derivatisation of the N-hydroxythiazole scaffold has the potential to afford selective inhibitors for 2OG oxygenases other than FIH
Cellular Mechanisms Underlying the Laxative Effect of Flavonol Naringenin on Rat Constipation Model
BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM) elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC)), which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid), but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid). Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride) pretreatment reduced the naringenin-induced I(SC). In addition, significant inhibition of the naringenin-induced I(SC) by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator) was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation
Influence of the CYP2D6 polymorphism and hemodialysis on codeine disposition in patients with end-stage renal disease
Synthesis and characterization of tungsten-incorporated mesoporous molecular sieve MCM-48 by one step
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Hybrid grey model to forecast monitoring series with seasonality
The grey forecasting model has been successfully applied to many fields. However, the precision of GM(1,1) model is not high. In order to remove the seasonal fluctuations in monitoring series before building GM (1, 1) model, the forecasting series of GM(1, 1) was built, and an inverse process was used to resume the seasonal fluctuations. Two deseasonalization methods were presented, i.e., seasonal index-based deseasonalization and standard normal distribution-based deseasonalization. They were combined with the GM(1, 1) model to form hybrid grey models. A simple but practical method to further improve the forecasting results was also suggested. For comparison, a conventional periodic function model was investigated. The concept and algorithms were tested with four years monthly monitoring data. The results show that on the whole the seasonal index-GM(l,l) model outperform the conventional periodic function model and the conventional periodic function model outperform the SND-GM(l, 1) model. The mean absolute error and mean square error of seasonal index-GM(l, 1) are 30.69 % and 54.53 % smaller than that of conventional periodic function model, respectively. The high accuracy, straightforward and easy implementation natures of the proposed hybrid seasonal index-grey model make it a powerful analysis technique for seasonal monitoring series
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