CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A2A Receptor-Mediated Control of Fear Memory and Amygdala Plasticity

Adenosine A_2A receptors (A_2AR) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A_2AR activation is ensured by ATP-derived extracellular adenosine formed by ecto-5′-nucleotidase or CD73. We now tested whether CD73 is also responsible to provide for the activation of A_2AR in controlling fear memory and amygdala long-term potentiation (LTP). The bilateral intracerebroventricular injection of the CD73 inhibitor αβ-methylene ADP (AOPCP, 1 nmol/ventricle/day) phenocopied the effect of the A_2AR blockade by decreasing the expression of fear memory, an effect disappearing in CD73-knockout (KO) mice and in forebrain neuronal A_2AR-KO mice. In the presence of PPADS (20 μM) to eliminate any modification of ATP/ADP-mediated P2 receptor effects, both AOPCP (100 μM) and the A_2AR antagonist, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 (50 nM), decreased LTP magnitude in synapses of projection from the external capsula into the lateral amygdala, an effect eliminated in slices from both forebrain neuronal A_2AR-KO mice and CD73-KO mice. These data indicate a key role of CD73 in the process of A_2AR-mediated control of fear memory and underlying synaptic plasticity processes in the amygdala, paving the way to envisage CD73 as a new therapeutic target to interfere with abnormal fear-like emotional processing.     

In Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators

ABCB11 is responsible for biliary bile acid secretion at the canalicular membrane of hepatocytes. Variations in the ABCB11 gene cause a spectrum of rare liver diseases. The most severe form is progressive familial intrahepatic cholestasis type 2 (PFIC2). Current medical treatments have limited efficacy. Here, we report the in vitro study of Abcb11 missense variants identified in PFIC2 patients and their functional rescue using cystic fibrosis transmembrane conductance regulator potentiators. Three ABCB11 disease-causing variations identified in PFIC2 patients (i.e., A257V, T463I and G562D) were reproduced in a plasmid encoding an Abcb11-green fluorescent protein. After transfection, the expression and localization of the variants were studied in HepG2 cells. Taurocholate transport activity and the effect of potentiators were studied in Madin–Darby canine kidney (MDCK) clones coexpressing Abcb11 and the sodium taurocholate cotransporting polypeptide (Ntcp/Slc10A1). As predicted using three-dimensional structure analysis, the three variants were expressed at the canalicular membrane but showed a defective function. Ivacaftor, GLP1837, SBC040 and SBC219 potentiators increased the bile acid transport of A257V and T463I and to a lesser extent, of G562D Abcb11 missense variants. In addition, a synergic effect was observed when ivacaftor was combined with SBC040 or SBC219. Such potentiators could represent new pharmacological approaches for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the function of the transporter.     

The effect of royal jelly and propolis alone and in combination on inhibition of Aspergillus parasiticus growth,aflatoxin production,and aflR gene expression

The objective of this study was to determine the inhibitory effect of royal jelly (RJ) and propolis on growth, aflatoxin production and aflR gene expression in Aspergillus parasiticus. Inhibitory effect of RJ and propolis against a standard strain of A. parasiticus(ATCC 15517) was determined alone and in combination in accordance with the CLSI M38-A2 and checkerboard methods, respectively. The aflatoxin concentrations in the control and treated media were determined by HPLC. Also, the quantitative changes in the aflR gene expression were analyzed. The minimum inhibitory concentrations (MIC) of RJ and propolis alone were 3,200 and 100μg/ml, respectively. Also, the MICs of RJ and propolis in combination were 200 and 25μg/ml, respectively. When combined, a synergistic interaction was observed with a FICI of 0.312. Total levels of aflatoxin decreased from 386.1ppm to 8.72, 3.01 and 1.75ppm at 1,600μg/ml of RJ, 50μg/ml of propolis and 100+12.5μg/ml of RJ and propolis, respectively. In addition, the level of afIR gene expression was significantly decreased after treatment with RJ and propolis extracts alone and with their combination. The findings reveal that RJ and propolis extracts, either alone or in combination, have a significant inhibitory effect on aflR gene expression in aflatoxin production.     

The excellent photocatalytic activity of novel Cs3PW12O40/WO3 composite toward the degradation of rhodamine B

In this paper, a simple one-pot thermal decomposition method was successfully used to synthesize a novel Cs₃PW₁₂O₄₀/WO₃ composite for the first time. The synthesized composite was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), FTIR, diffuse reflectance spectroscopy (DRS) and N₂ adsorption-desorption techniques. The photocatalytic activity to degrade RhB molecules over Cs₃PW₁₂O₄₀/WO₃ composite was evaluated under xenon light irradiation. The results indicated the complete degradation of RhB molecules over Cs₃PW₁₂O₄₀/WO₃ composite after 30?min irradiation. However, the photocatalytic degradation of RhB over WO₃ and Cs₃PW₁₂O₄₀ after 80?min light irradiation are nearly 52%, and 68%, respectively. The enhanced photocatalytic activity of Cs₃PW₁₂O₄₀/WO₃ composite compared with WO₃, and Cs₃PW₁₂O₄₀ was ascribed to the strong interaction between WO₃ and Cs₃PW₁₂O₄₀, which effectively reduces the recombination of photogenerated electron-hole pairs. Based on experimental results, the possible mechanism of photocatalytic reactions on the Cs₃PW₁₂O₄₀/WO₃ composite photocatalyst was investigated, and the hydroxyl radical (OH) and superoxide radical (O₂^?) were determined as the main active species in the photocatalytic degradation of RhB over Cs₃PW₁₂O₄₀/WO₃ composite.     

Polyacrylamide hydrogel application in sand control with compressive strength testing

Sand production is one of the major problems in sandstone reservoirs. Different mechanical and chemical methods have been proposed to control sand production. In this paper, we propose a chemical method based on using polyacrylamide/chromium triacetate hydrogel to investigate sand production in a synthetic sandpack system. To this end, a series of bulk experiments including the bottle test and rheological analysis along with compression tests were conducted. Experimental results indicated that the compressive strength of the sandpack was increased as much as 30 times by injecting 0.5 pore volume of hydrogel. Also, it was found that the increases in cross-linker and polymer concentrations exhibited a positive impact on the compressive strength of the sandpack, mostly by cross-linker concentration(48 psi). Hydrogel with a higher value of cross-linker could retain its viscoelastic properties against the strain which was a maximum of 122% for 0.5 weight ratio of cross-linker/polymer. The presence of salts, in particular divalent cations, has a detrimental effect on the hydrogel stability. The maximum strain value applied on hydrogel in the presence of CaCl_2 was only about 201% as compared to 1010% in the presence of distilled water. Finally, thermogravimetric analysis and its derivative showed that the hydrogel could retain its structure up to 300 °C. The results of this study revealed the potential application of the hydrogel to control sand production.     

Incremental learning framework for real‐world fraud detection environment

For detecting malicious bidding activities in e‐auctions, this study develops a chunk‐based incremental learning framework that can operate in real‐world auction settings. The self‐adaptive framework first classifies incoming bidder chunks to counter fraud in each auction and take necessary actions. The fraud classifier is then adjusted with confident bidders' labels validated via bidder verification and one‐class classification. Based on real fraud data produced from commercial auctions, we conduct an extensive experimental study wherein the classifier is adapted incrementally using only relevant bidding data while evaluating the subsequent adjusted models' detection and misclassification rates. We also compare our classifier with static learning and learning without data relevancy.     

Nanotechnology-based combinational drug delivery systems for breast cancer treatment

Modern chemotherapeutic anticancer treatments have come a long way in the fight against breast cancer, thus bringing science closer to a cure. However, the nature of these drugs is to attack both cancerous and non-cancerous cells at the same time. In our studies, we synthesized Magnetic Cyclodextrin-polyurethane based nano-composite (Fe₃O₄-ECA-PU-CD) which is a drug delivery system using a biocompatible magnetic polymer that directs chemotherapeutic drugs to cancerous regions in the body with an external magnet. This nano-composite was able to facilitate the loading and simultaneous release of the hydrophilic antitumor drug Doxorubicin (DOX) along with the hydrophobic antitumor drug docetaxel. The composite was made using a simple co-precipitation method with magnetic nano-particles (MNPs) followed by a silica coating process and an in situ polymerization process. Verification of synthesis for the drug carrier was carried out using techniques such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and a vibrating sample magnetometer (VSM) to measure magnetic properties. Drug loading and release efficiencies were monitored using an HPLC-UV detector. Finally, an MTT assay was performed in order to evaluate the biocompatibility and toxicity of the synthetic nano-composite on MCF7 cell lines. Our findings present a new biocompatible drug delivery system with a high capacity for loading and directing two different chemotherapeutic drugs simultaneously to cancer sites with little to no toxicity to the surrounding non-cancerous cells. These studies present a viable tool for cancer treatment and research where the cancer is efficiently removed while the patient remains healthy.     

Characterization and reactivity of VMgO catalysts prepared by wet impregnation and sol–gel methods

This paper reports the study of physicochemical, surface, and catalytic properties of two series of VMgO catalysts prepared by two different methods: wet impregnation and sol–gel. The characterizations of the elaborated materials were performed using N₂-sorption (Brunauer, Emmett and Teller (BET)), X-ray diffraction, Raman, transmission electron microscopy–energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy analyses. The catalytic properties of the elaborated materials were investigated in the isopropanol decomposition reaction to determine their acid–base character and in the selective oxidation of n-butane to evaluate their dehydrogenation properties. The preparation method and vanadium content strongly affected the properties of our materials. The sol–gel method leads to smaller crystallite size, higher specific surface area, and uniform particle distribution compared to the impregnation one. Both impregnation and SG solids promote the formation of acetone, which is related to the presence of strong basic sites (O^2? species) on the catalytic exposed surface. The more pronounced basic character was obtained through the SG samples. The sol–gel samples exhibited the highest catalytic activity and C4-olefin selectivity in the partial oxidation of n-butane. Whatever the preparation procedure, the nature of surface oxygen species plays an important role in the orientation of catalytic performances.