Strategies To Design Selective Histone Deacetylase Inhibitors

This review classifies drug-design strategies successfully implemented in the development of histone deacetylase (HDAC) inhibitors, which have many applications including cancer treatment. Our focus is on especially demanded selective HDAC inhibitors and their structure-activity relationships in relation to corresponding protein structures. The main part of the paper is divided into six subsections each narrating how optimization of one of six structural features can influence inhibitor selectivity. It starts with the impact of the zinc binding group on selectivity, continues with the optimization of the linker placed in the substrate binding tunnel as well as the adjustment of the cap group interacting with the surface of the protein, and ends with the addition of groups targeting class-specific sub-pockets: the side-pocket-, lower-pocket- and foot-pocket-targeting groups. The review is rounded off with a conclusion and an outlook on the future of HDAC inhibitor design.     

Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Use of Time Series Analysis to Evaluate the Impacts of Underground Mining on the Hydraulic Properties of Groundwater of Dysart Woods,Ohio

Mine Water and the Environment - Dysart Woods is the largest (≈ 23 ha) old-growth forest in southeastern Ohio. It was donated to Ohio University for research purpose and public...     

Graphene oxide conversion into controllably carboxylated graphene layers via photoreduction process in the inert atmosphere

Abstract

The one-step method for graphene oxide (GO) simultaneous reduction and carboxylation via ultraviolet irradiation in the inert atmosphere has been reported. X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) data revealed that the proposed approach allows to obtain reduced graphene oxide (rGO) films, containing up to 10 at.% of carboxyl groups. The carboxyl groups concentration can be tuned within the range of 3 to 10 at.% by controlling the oxidation degree of the irradiated GO via the preliminary low-temperature air heating. Furthermore, no carboxylation effect is observed in the case of irradiation of the completely reduced GO films. This coincides with our previous results, validating the proposed model of GO carboxylation based on photoinduced conversion of basal-plane hydroxyl groups and ketones into carboxyl ones. Despite a different degree of carboxylation, all the obtained samples demonstrate almost complete elimination of basal plane groups and restoration of the graphene flakes aromatic structure. This fact is emphasized by the sheet resistance measurements, demonstrating that the obtained C-xy graphene exhibits high electrical conductivity. As a net result, the material obtained by the presented method shows promising applications in the manufacturing of biosensor transducers owing to both its conductive nature and presence of carboxyl groups, playing the role of the anchoring points for biomolecules.     

Prebiotic properties of xylooligosaccharide extracted from sugarcane wastes (pith and rind): a comparative study

Wastes from agricultural industry are often disposed. Nevertheless, these wastes contain nutraceuticals and functional compounds. Xylooligosaccharide (XOS) was extracted from two sugarcane wastes (SW); rind (SR) and pith (SP), and the prebiotic properties of both XOS were examined. SR and SP had different mixture of XOS and were resistant towards α-amylase and gastric juice digestion in vitro. Although the growth of Lactobacillus casei Shirota (LcS) and Bifidobacterium animalis subsp. Lactis ATCC® 700541™ increased significantly in both XOS after 48 h of incubation, XOS from SR showed better enrichment of probiotics growth. Both XOS were found to be more fermentable by LcS and acetic acid was the predominant end product of the fermentation. Since XOS composition was different between SR and SP and such difference can affect their prebiotic properties, it is important to choose the appropriate parts of SW to extract XOS with high fermentable properties and obtain the best synbiotics combination.     

Possibilities of the Computer-Controlled Detonation Spraying method: A chemistry viewpoint

This article is aimed to discuss the chemical aspects of detonation spraying of powder materials. In this method of coating deposition, ceramic, metallic or composite powders are injected into the barrel of a detonation gun filled with an explosive gaseous mixture. When the latter is ignited, the powders are heated and accelerated toward the substrate. Subjected to high temperatures, the powders are prone to chemical reactions, the reaction products possibly becoming the major phase constituents of the coatings. What types of reactions are possible? Can these reactions be carried out in a controlled manner? We answer these questions considering the interactions of the sprayed powders with the gaseous environment of the barrel as well as those between the phases of a composite feedstock powder. In Computer-Controlled Detonation Spraying (CCDS), the explosive charge and stoichiometry of the fuel-oxygen mixtures are precisely measured and can be flexibly changed. Our studies demonstrate that with the introduction of a highly flexible process of CCDS, detonation spraying has entered a new development stage, at which it can be considered as a powerful method of composition and microstructure tailoring of thermally sprayed coatings. During CCDS of TiO₂-containing powders, chemical reduction of titanium dioxide can be carried out to different levels to form either oxygen-deficient TiO_2−x or Ti₃O₅ suboxide. CCDS of Ti₃Al can produce titanium oxide coatings when oxidation by the detonation products dominates or titanium nitride-titanium aluminide coatings when oxidation is hindered but the interaction of the powders with nitrogen—a carrier gas component—is favored. During detonation spraying of Ti₃SiC₂–Cu composites, the Ti₃SiC₂ phase is preserved only in cold conditions; otherwise, Si de-intercalates from the Ti₃SiC₂ phase and dissolves in Cu resulting in the formation of the TiC_x–Cu(Si) composite coatings.     

新古典主义建筑在中国和西方

该文首先提出与古典主义相对应的新古典主义概念,接着对在中国和西方发生的四次新古典主义建筑现象从时间,社会背景,建筑风格,建筑类型,当时的社会需求和社会意义等方面进行分析比较,最后通过时间上的纵向比较和空间上的横向比较得出结论。从而对时下流行的“新古典主义”一词,进行全面的理解和把握。