Development of Potent Adenosine Monophosphate Activated Protein Kinase (AMPK) Activators

Previously, we reported the identification of a thiazolidinedione‐based adenosine monophosphate activated protein kinase (AMPK) activator, compound 1 (N‐[4‐({3‐[(1‐methylcyclohexyl)methyl]‐2,4‐dioxothiazolidin‐5‐ylidene}methyl)phenyl]‐4‐nitro‐3‐(trifluoromethyl)benzenesulfonamide), which provided a proof of concept to delineate the intricate role of AMPK in regulating oncogenic signaling pathways associated with cell proliferation and epithelial–mesenchymal transition (EMT) in cancer cells. In this study, we used 1 as a scaffold to conduct lead optimization, which generated a series of derivatives. Analysis of the antiproliferative and AMPK‐activating activities of individual derivatives revealed a distinct structure–activity relationship and identified 59 (N‐(3‐nitrophenyl)‐N′‐{4‐[(3‐{[3,5‐bis(trifluoromethyl)phenyl]methyl}‐2,4‐dioxothiazolidin‐5‐ylidene)methyl]phenyl}urea) as the optimal agent. Relative to 1 , compound 59 exhibits multifold higher potency in upregulating AMPK phosphorylation in various cell lines irrespective of their liver kinase B1 (LKB1) functional status, accompanied by parallel changes in the phosphorylation/expression levels of p70S6K, Akt, Foxo3a, and EMT‐associated markers. Consistent with its predicted activity against tumors with activated Akt status, orally administered 59 was efficacious in suppressing the growth of phosphatase and tensin homologue (PTEN)‐null PC‐3 xenograft tumors in nude mice. Together, these findings suggest that 59 has clinical value in therapeutic strategies for PTEN‐negative cancer and warrants continued investigation in this regard.     

Liquid flow in polyurethane foams for filtration applications: a study on their characterization and permeability estimation

Journal of Porous Materials - Open-cell polyurethane foams have been investigated for various filtration applications to treat industrial byproducts and waste water. Flow-related morphological...     

Polymeric nanofibers containing solid nanoparticles prepared by electrospinning and their applications

Generally, polymer solution or sol–gel is used to produce electrospun nanofibers via the electrospinning technique. In the utilized sol–gel, the metallic precursor should be soluble in a proper solvent since it has to hydrolyze and polycondensate in the final solution; this strategy straitens the applications of the electrospinning process and limits the category of the electrospinnable materials. In this study, we are discussing electrospinning of a colloidal solution process as an alternative strategy. We have utilized many solid nanopowders and different polymers as well. All the examined colloids have been successfully electrospun. According to the SEM and FE SEM analyses for the obtained nanofiber mats, the polymeric nanofibers could imprison the small nanoparticles; however, the big size ones were observed attaching the nanofiber mats. Successfully, the proposed strategy could be exploited to prepare polymeric nanofibers incorporating metal nanoparticles which might have interesting properties compared with the pristine. For instance, PCL/Ti nanofiber mats exhibited good bioactivity compared with pristine PCL. The proposed strategy can be considered as an innovated methodology to prepare a new class of the electrospun nanofiber mats which cannot be obtained by the conventional electrospinning technique.     

Functionalization of Electrospun Titanium Oxide Nanofibers with Silver Nanoparticles: Strongly Effective Photocatalyst

In the present study, we are introducing silver-doped titanium oxide nanofibers produced by electrospinning technique. Calcination of dry nanofiber mats consisting of silver nitrate–titanium isopropoxide/PVAc in air at 600°C for 1 h leads to produce Ag-doped titania nanofibers. Two dyes have been invoked to check the photocatalytic ability of the produced nanofibers; methylene blue dihydrate and methyl red. The obtained results indicated that the silver-doped titanium oxide nanofibers can eliminate >92% of the methylene blue dye within 10 min only. In a case of methyl red, almost the dye was decayed (93%) within 3 h.     

One‐Pot Thioetherification of Aryl Halides Using Thiourea and Alkyl Bromides Catalyzed by Copper(I) Iodide Free from Foul‐Smelling Thiols in Wet Polyethylene Glycol (PEG 200)

In this article, we have developed a new protocol for the thioarylation of structurally diverse alkyl bromides such as benzyl, cinnamyl, n‐octyl, cyclohexyl, cyclopentyl, and tert‐butyl bromides with aryl iodides, bromides and an activated chloride using thiourea catalyzed by copper(I) iodide in wet polyethylene glycol (PEG 200) as an eco‐friendly medium in the presence of potassium carbonate at 80 and 100 °C under an inert atmosphere. The process is free from foul‐smelling thiols which makes this method more practical for the thioetherification of aryl halides. Another important feature of this method is the variety of alkyl bromides which are commercially available for the in situ generation of thiolate ions with respect to the existing protocols in which the less commercially available thiols are directly used for the preparation of arylthio ethers.     

Optimization of peroxidase-catalyzed oxidative coupling process for phenol removal from wastewater using response surface methodology

Hydroxylated aromatic compounds (HACs) are considered to be primary pollutants in a wide variety of industrial wastewaters. Horseradish peroxidase (HRP) is suitable for the removal of these toxic substances. However, development of a mathematical model and optimization of the HRP-based treatment considering the economical issues by novel methods is a necessity. In the present study, optimization of phenol removal from wastewater by horseradish peroxidase (HRP) was carried out using response surface methodology (RSM) and central composite design (CCD). As the initial experimental design, 2(4-1) half-fraction factorial design (H-FFD) is accomplished in triplicate at two levels to select the most significant factors and interactions in the phenol removal procedure. Temperature (degrees C), pH, concentration of enzyme (unit mL(-1)), and H202 (mM) were determined as the most effective independent variables. Finally, a fourfactor-five coded level CCD, 30 runs, was performed in order to fit a second-order polynomial function to the results and calculate the economically optimum conditions of the reaction. The goodness of the model was checked by different criteria including the coefficient of determination (R2 = 0.93), the corresponding analysis of variance ((Pmodel > F) < 0.0001) and parity plot (r = 0.96). These analyses indicated that the fitted model is appropriate for this enzymatic system. With the assumption that the minimum enzyme concentration was 0.26 unit mL(-1), the analysis of the response surface contour and surface plots defined the optimum conditions as follows: pH = 7.12, hydrogen peroxide concentration 1.72 mM, and 10 degrees C. This work improves phenol removal operation economically by applying minimum enzyme concentration and highest removal in comparison with previous studies.     

Synthesis of zirconium tungstate–zirconia core–shell composite particles

In this work, ZrW₂O₈–ZrO₂ core–shell composite particles were synthesized. ZrW₂O₈ that was used in the core is a material with negative coefficient of thermal expansion, and it was synthesized from a high-pH precursor based on use of tungstic acid and zirconium acetate. Shell layer was composed of ZrO₂ nanocrystallites and precipitated from an aqueous solution by urea hydrolysis. While volume of the shell was effectively controlled by the initial zirconium ion concentration in the solutions, the rate of precipitation was a function of the ratio of initial concentrations of urea to zirconium ions. It is hypothesized that isolation of the ZrW₂O₈ within a layer of ZrO₂, will be a key element in solving problems associated with reactivity of ZrW₂O₈ towards other components in sintering of ceramic–ceramic composites with tuned or zero thermal expansion coefficient.     

Three‐dimensional multiphase flow model to study channel flow dynamics of PEM fuel cells

A three‐dimensional multiphase flow model has been developed to study dynamics of a water droplet on the surface of the channel of proton exchange membrane fuel cell. Results are presented based on solving full Navier–Stokes equations for Newtonian liquids. The volume‐of‐fluid method is used to numerically determine the deformation of free surfaces. Water droplet and channel fluid properties determine whether the droplet deforms and remain stationary or disintegrate. We have shown the dependency of the water flooding to the flow rate and pressure drop in the channel has been introduced as a tool to determine water flooding in the channel. Copyright © 2010 John Wiley & Sons, Ltd.