Synthesis and Photocatalytic Properties of Single Crystalline (Ga1-xZnx)(N1-xOx) Nanotubes

Recently, (Ga_1-xZn_x)(N_1-xO_x) has gained widespread attention as a comparatively high efficiency photocatalyst for visible-light-driven overall water splitting. Despite significant gains in efficiency over the past several years, a majority of the photogenerated carriers recombine within bulk powders. To improve the photocatalytic activity, we used an epitaxial casting method to synthesize single-crystalline, high surface area (Ga_1-xZn_x)(N_1-xO_x) nanotubes with ZnO compositions up to x=0.10. Individual nanotubes showed improved homogeneity over powder samples due to a well defined epitaxial interface for ZnO diffusion into GaN. Absorption measurements showed that the ZnO incorporation shifts the absorption into the visible region with a tail out to 500 nm. Gas chromatography (GC) was used to compare the solar water splitting activity of (Ga_1-xZn_x)(N_1-xO_x) nanotubes (x=0.05–0.10) with similar composition powders. Cocatalyst decorated samples were dispersed in aqueous solutions of CH₃OH and AgO₂CCH₃ to monitor the H⁺ reduction and H₂O oxidation half reactions, respectively. The nanotubes were found to have approximately 1.5–2 times higher photocatalytic activity than similar composition powders for the rate limiting H⁺ reduction half reaction. These results demonstrate that improvements in homogeneity and surface area using the nanotube geometry can enhance the photocatalytic activity of GaN:ZnO for solar water splitting.     

Increased Activity of Cell Surface Peptidases in HeLa Cells Undergoing UV-Induced Apoptosis Is Not Mediated by Caspase 3

We have previously shown that in HeLa cells treated with a variety of agents there is an increase in cell surface peptidase (CSP) activity in those cells undergoing apoptosis. The increase in CSP activity observed in UVB-irradiated cells undergoing apoptosis was unaffected when the cultures were treated with the aminopeptidase inhibitor bestatin, and matrix metalloprotease inhibitor BB3103, but greatly enhanced when treated with the caspase 3 inhibitor-DEVD, and reduced in the presence of the poly(ADP-ribose) polymerase (PARP) inhibitor-3-aminobenzamide (3AB). Neither 3AB nor DEVD had an effect on the gross morphology of the apoptotic cells observed under electron microscopy, nor did they have an effect on phosphatidylserine eversion on the cell membrane, or that of PARP cleavage. All the agents except for DEVD had no effect on the level of caspase 3 activity in the cells. The results suggest that other caspases may cleave PARP in these cells. Both 3AB and DEVD treatment reduced the level of actin cleavage seen in the apoptotic cells. The increase in CSP activity observed in cells undergoing UVB-induced apoptosis appears to involve PARP but not caspase 3.     

From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs

The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (f_u brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 .     

Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis

Genomic instability is generally considered as a hallmark of tumorigenesis and a prerequisite condition for malignant transformation. Aluminium salts are suspected environmental carcinogens that transform mammary epithelial cells in vitro through unknown mechanisms. We report here that long-term culture in the presence of aluminium chloride (AlCl₃) enables HC11 normal mouse mammary epithelial cells to form tumours and metastases when injected into the syngeneic and immunocompetent BALB/cByJ strain. We demonstrate that AlCl₃ rapidly increases chromosomal structural abnormalities in mammary epithelial cells, while we failed to detect direct modulation of specific mRNA pathways. Our observations provide evidence that clastogenic activity—a well-recognized inducer of genomic instability—might account in part for the transforming abilities of aluminium in mammary epithelial cells.     

The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress,and Inflammation in Protective and Adaptive Responses

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.     

Countercurrent approach to the enrichment of Δ9c,11t-and Δ10t,12c-18:2 isomers by urea complexation

CLA refers to a group of geometrical and positional isomers of linoleic acid. CLA has been shown to have potentially beneficial effects on cancer, atherosclerosis, and body metabolism in animals. Mixtures containing equal amounts of these isomers are commonly used in many research studies because of their greater availability and lower cost relative to pure isomers. This has hindered progress in elucidating the biological properties of specific isomers and their relevance in animal and human biology. A method was developed that offers a compromise between cost and utility to make available enriched mixtures of either the Δ9c,11t- or Δ10t,12c-18:2 isomers for use in a wide range of experimental applications. A countercurrent approach was developed to separate the Δ9c,11t- and Δ10t,12c-18:2 isomers from an equal mixture of these two isomers by urea complexation. After three successive rounds of complexation using an equal amount of CLA and urea, a fraction enriched in Δ9c,11t-18:2 containing 42.5 and 17.4% of Δ9c,11t-and Δ10t,12c-18:2, respectively, was recovered. After a single round of complexation using 2.5 g urea/g CLA, a fraction enriched in Δ10t,12c-18:2 was recovered containing 29.7 and 69.1% of Δ9c,11t- and Δ10t,12c-18:2, respectively.     

Solvent effect modelling of isocyanuric products synthesis by chemometric methods

Chemometric tools were used to generate the modelling of solvent e inverted exclamation markects on the N-alkylation of an isocyanuric acid salt. The method proceeded from a central composite design applied on the Carlson solvent classification using principal components analysis. The selectivity of the reaction was studied from the production of different substituted isocyanuric derivatives. Response graphs were obtained for each compound and used to devise a strategy for solvent selection. The prediction models were validated and used to search for the best selectivity for the reaction system. The solvent most often selected as the best for the reaction is the N,N-dimethylformamide.     

Apatitic calcium phosphates used in compression: rationalization of the end-use properties

Different apatitic calcium phosphates used as direct compression excipients have been developed in the last years. The difficulty to obtain reproducible synthesis explains their approximative and irregular composition. TRI-TAB® commercial grade called anhydrous tricalcium phosphate is associated to a chemical formula corresponding to a mixture of tricalcium phosphate (Ca₃(PO₄)₂) and calcium hydroxide (Ca(OH)₂). The chemical analysis shows that it is hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂).

The purpose of this work is to rationalize the chemical and physical natures of apatitic calcium phosphates used in direct compression, and thus their technological properties. Apatitic calcium phosphates differing in their Ca/P molar ratio (from 1.500 i.e. tricalcium phosphate to 1.667 i.e. hydroxyapatite) have been synthesized and their compression properties have been analysed. The results have been compared to those of TRI-TAB®. They pointed out the importance of the chemical nature contribution. Tricalcium phosphate-based materials exhibited an excellent compactibility when not calcined. Uncalcined hydroxyapatite had similar properties than TRI-TAB®, that is intermediate. Calcined tricalcium phosphate and hydroxyapatite showed a low compaction ability. It appears that the perfect chemical and physical control of the material is important in particle design to rationalize and optimise the tablet formulation as well as the process.     

Polymer/layered silicate nanocomposites by combined intercalative polymerization and melt intercalation: a masterbatch process

Poly(ε-caprolactone) (PCL) and poly(vinyl chloride) (PVC) layered silicate nanocomposites were prepared by combination of intercalative polymerization and melt intercalation. In a first step, high clay content PCL nanocomposites were prepared by in situ polymerization of ε-caprolactone intercalated between selected organo-modified silicate layers. The polymerization was catalyzed with dibutyltin dimethoxide in the presence of montmorillonites, the surface of which were previously exchanged with (functionalized) long alkyl chains ammonium cations. Then, these highly filled PCL nanocomposites were added as masterbatches in commercial PCL and PVC by melt blending. The intercalation of PCL chains within the silicate layers by in situ polymerization proved to be very efficient, leading to the formation of intercalated and/or exfoliated structures depending on the organo-clay. These masterbatches were readily dispersed into the molten PCL and PVC matrices yielding intercalated/exfoliated layered silicate nanocomposites which could not be obtained by melt blending the matrix directly with the same organo-modified clays. The formation of nanocomposites was assessed both by X-ray diffraction and transmission electronic microscopy. Interestingly, this so-called ‘masterbatch’ two-step process allowed for preparing PCL nanocomposites even with non-modified natural clay, i.e. sodium montmorillonite, which showed a material stiffness much higher than the corresponding microcomposites recovered by direct melt intercalation. The thermal stability of PCL nanocomposites as a function of clay content was investigated by thermogravimetry (TGA).     

Diastereoselective Heterogeneous Catalytic Hydrogenation of Aromatic or Heteraromatic Compounds

The diastereoselective hydrogenation catalyzed by heterogeneous metallic catalysts uses a covalently bound chiral auxiliary to induce the chirality. It remains an active synthetic methodology in the asymmetric synthesis of chiral products and may proceed with high diastereoselectivity. This review describes recent examples using this method, such as hydrogenation of C=C, C=O, and C=N bonds. The use of a chiral auxiliary group has also been successfully applied to the hydrogenation of aromatic and heteroaromatic rings. The choice of the chiral auxiliary was found to play a key role in the asymmetric hydrogenation. The results could be explained in terms of steric effect, with a preferred conformation of the adduct substrate and the addition occurring from the less bulky side. The catalytic metal, the support and the presence of additives were also found to have a significant influence.