Phenotypic Discovery of SB1501, an Anti-obesity Agent,through Modulating Mitochondrial Activity

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.     

Charge Transportation and Chirality in Liquid Crystalline Helical Network Phases of Achiral BTBT-Derived Polycatenar Molecules

First examples of multichain (polycatenar) compounds, based on the π-conjugated [1]benzothieno[3,2-b]benzothiophene unit are designed, synthesized, and their soft self-assembly and charge carrier mobility are investigated. These compounds, terminated by the new fan-shaped 2-brominated 3,4,5-trialkoxybenzoate moiety, form bicontinuous cubic liquid crystalline (LC) phases with helical network structure over extremely wide temperature ranges (>200 K), including ambient temperature. Compounds with short chains show an achiral cubic phase with the double network, which upon increasing the chain length, is at first replaced by a tetragonal 3D phase and then by a mirror symmetry is broken triple network cubic phase. In the networks, the capability of bypassing defects provides enhanced charge carrier mobility compared to imperfectly aligned columnar phases, and the charge transportation is non-dispersive, as only rarely observed for LC materials. At the transition to a semicrystalline helical network phase, the conductivity is further enhanced by almost one order of magnitude. In addition, a mirror symmetry broken isotropic liquid phase is formed beside the 3D phases, which upon chain elongation is removed and replaced by a hexagonal columnar LC phase.     

Reusable and durable electrostatic air filter based on hybrid metallized microfibers decorated with metal-organic-framework nanocrystals

As global air pollution becomes increasingly severe,various types of fibrous filters have been devel-oped to improve air filter performance.However,fibrous filters have limitations such as high packing density that generally causes high-pressure drop and ultimately deterioration in the filtration effi-ciency.High-pressure particulate matter precipitators are limited in terms of scope for commercialization because they require high voltage supplies and ozone generators.In this study,we develop fibrous fil-ters with enhanced durability and improved performance using metallized microfibers decorated with metal-organic-framework(MOF)nanocrystals.Not only does the efficiency of the developed filters remain at or above 97％for 0.50-1.5 μm PMs but the durability also significantly increases.In addi-tion,using the water purification ability of the MOF,we explore the dye degradation effect of the hybrid microfibers by immersing them into Rhodamine B aqueous solution.In such an experiment the Rho-damine B aqueous solution is completely purified by the presence of the hybrid microfibers under the UV irradiation.     

Trans-differentiation of human adipose-derived mesenchymal stem cells into cardiomyocyte-like cells on decellularized bovine myocardial extracellular matrix-based films

In this study, we aimed at fabricating decellularized bovine myocardial extracellular matrix-based films (dMEbF) for cardiac tissue engineering (CTE). The decellularization process was carried out utilizing four consecutive stages including hypotonic treatment, detergent treatment, enzymatic digestion and decontamination, respectively. In order to fabricate the dMEbF, dBM were digested with pepsin and gelation process was conducted. dMEbF were then crosslinked with N-hydroxysuccinimide/1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (NHS/EDC) to increase their durability. Nuclear contents of native BM and decellularized BM (dBM) tissues were determined with DNA content analysis and agarose-gel electrophoresis. Cell viability on dMEbF for 3rd, 7th, and 14th days was assessed by MTT assay. Cell attachment on dMEbF was also studied by scanning electron microscopy. Trans-differentiation capacity of human adipose-derived mesenchymal stem cells (hAMSCs) into cardiomyocyte-like cells on dMEbF were also evaluated by histochemical and immunohistochemical analyses. DNA contents for native and dBM were, respectively, found as 886.11?±?164.85 and 47.66?±?0.09?ng/mg dry weight, indicating a successful decellularization process. The results of glycosaminoglycan and hydroxyproline assay, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), performed in order to characterize the extracellular matrix (ECM) composition of native and dBM tissue, showed that the BM matrix was not damaged during the proposed method. Lastly, regarding the histological study, dMEbF not only mimics native ECM, but also induces the stem cells into cardiomyocyte-like cells phenotype which brings it the potential of use in CTE.     

Thermodynamic performance analysis of three solid oxide fuel cell and gas microturbine hybrid systems for application in auxiliary power units

In this study, three different configurations of a solid oxide fuel cell and gas microturbine hybrid system are evaluated for application in auxiliary power units. The first configuration is a common hybrid system in auxiliary power units, utilizing a fuel cell stack in the structure of the gas turbine cycle. The other configurations use two series and parallel fuel cell stacks in the structure of the gas turbine cycle. The main purpose of this research is thermodynamic analysis, evaluation of the performance of the proposed hybrid systems in similar conditions, and selection of an appropriate system in terms of efficiency, power generation, and entropy generation rate. In this study, the utilized fuel cells were subjected to electrochemical, thermodynamic, and thermal analyses and their working temperatures were calculated under various working conditions. Results indicate that the hybrid system with two series stacks had maximum power generation and efficiency compared with the other two cases. Moreover, the simple hybrid system and the system with two parallel stacks had relatively equal pure power generation and efficiency. According to the investigations, hybrid system with two series fuel cell stacks, which had 3424 and 1712 cells, respectively, can achieve the electrical efficiency of over 48%. A hybrid system with two parallel fuel cell stacks, in which each stack had 2568 cells, had the electrical efficiency of 46.3%. Findings suggested that maximum electrical efficiency occurred between the pressure ratios of 5–6 in the proposed hybrid systems.     

Effect of sand and clay fouling on the shear strength of railway ballast for different ballast gradations

Ballast contamination by fine materials such as sand and clay in railway track at arid regions is an important issue that causes track instability problems and settlement due to reduction of shear strength of ballast. In this paper, the results of direct shear box test conducted on clean ballast, sand-fouled ballast and clay-fouled ballast for different ballast gradations are reported and discussed. For this purpose, three different fouling amounts according to fouling index are added to clean ballast. Test results show that by increasing the fouling percentage, the ballast shear strength always decreases both for sand and clay fouled ballast. However, the amount of shear strength reduction is low at high normal stresses. Clay contamination has more adverse effect on the shear strength of ballast compared with sand contamination. Also, the results of tests for evaluation of gradation effect on shear strength of fouled ballast which are conducted on various gradations according to American Railway Engineering and Maintenance-of-Way Association, show that the maximum particle size as well as uniformity coefficient affect the shear strength of ballast. Also, an empirical equation is presented to observe the effect of ballast gradation on reduction of shear strength with regard to amount of fouling material and normal stress.     

Pressure Management in Water Distribution Systems Using a Self-Tuning Controller to Distribute the Available Potable Water with Equality

The rapid population growth of cities in developing countries (DC) make difficult to distribute the available potable water (PW) with equality. The distribution problem arises from an insufficient amount of PW and because cities water distribution systems (WDS) are not efficient. The novelty of this paper is a self-tuning controller (STC) proposed to manage, along the day, the pressure of water through the nodes of a WDS. It means, pressure management (PM) is proposed to control water levels (WLs) in householders tanks (HTs). The objective is to satisfy with equality the PW demand at different zones of a city forcing the flow of water by managing the pressure. The proposed STC performance is tested on the digital simulator developed to characterize the hydraulic operation of a WDS. The dynamic behaviour of the WDS is determined by the variation of the WL in the tanks of the WDS when water is supplied or extracted from them. The WDS of Mexico City is analysed and the proposed STC is applied to a simplified WDS. The results allow to conclude that the proposed STC could become a supporting tool for the decision making of WDS operators.     

Imaging of two-dimensional unsaturated moisture flows in uncracked and cracked cement-based materials using electrical capacitance tomography

The development of visualizing tools to monitor unsaturated moisture flow in cement-based materials is of great importance, as most degradation processes in cement-based materials are connected to and take place in the presence moisture. This paper investigates the ability of electrical capacitance tomography (ECT) to image two-dimensional (2D) unsaturated moisture flow in cement-based materials. In ECT, the electrical permittivity distribution within an object is reconstructed based on measured capacitances between electrodes attached on the object’s surface. In a series of experiments, mortar specimens with and without discrete cracks were imaged with ECT during a 2D moisture ingress. The results show that ECT is able to monitor the evolution of the moisture flow, and to approximate the shape and position of the moisture front. These findings indicate that ECT is a viable method for monitoring and visualizing 2D unsaturated moisture flow in cement-based materials in the presence and absence of discrete cracks.