Synthesis and biological evaluation of tert-butyl ester and ethyl ester prodrugs of L-γ-methyleneglutamic acid amides for cancer.

In cancer cells, glutaminolysis is the primary source of biosynthetic precursors. Recent efforts to develop amino acid analogues to inhibit glutamine metabolism in cancer have been extensive. Our lab recently discovered many L-γ-methyleneglutamic acid amides that were shown to be as efficacious as tamoxifen or olaparib in inhibiting the cell growth of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells after 24 or 72 h of treatment. None of these compounds inhibited the cell growth of nonmalignant MCF-10A breast cells. These L-γ-methyleneglutamic acid amides hold promise as novel therapeutics for the treatment of multiple subtypes of breast cancer. Herein, we report our synthesis and evaluation of two series of tert-butyl ester and ethyl ester prodrugs of these L-γ-methyleneglutamic acid amides and the cyclic metabolite and its tert-butyl esters and ethyl esters on the three breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 and the nonmalignant MCF-10A breast cell line. These esters were found to suppress the growth of the breast cancer cells, but they were less potent compared to the L-γ-methyleneglutamic acid amides. Pharmacokinetic (PK) studies were carried out on the lead L-γ-methyleneglutamic acid amide to establish tissue-specific distribution and other PK parameters. Notably, this lead compound showed moderate exposure to the brain with a half-life of 0.74 h and good tissue distribution, such as in the kidney and liver. Therefore, the L-γ-methyleneglutamic acid amides were then tested on glioblastoma cell lines BNC3 and BNC6 and head and neck cancer cell lines HN30 and HN31. They were found to effectively suppress the growth of these cancer cell lines after 24 or 72 h of treatment in a concentration-dependent manner. These results suggest broad applications of the L-γ-methyleneglutamic acid amides in anticancer therapy.

Isolation of Two Plasticizers, Bis(2-ethylhexyl) Terephthalate and Bis(2-ethylhexyl) Phthalate, from Capparis spinosa L. Leaves.

Many plants have been known to be contaminated and accumulate plasticizers from the environment, including water sources, soil, and atmosphere. Plasticizers are used to confer elasticity and flexibility to various fiber and plastic products. Consumption of plasticizers can lead to many adverse effects on human health, including reproductive and developmental toxicity, endocrine disruption, and cancer. Herein, we report for the first time that two plasticizers, bis(2-ethylhexyl) terephthalate (DEHT) and bis(2-ethylhexyl) phthalate (DEHP), have been isolated from the leaves of Capparis spinosa L. (the caper bush), a plant that is widely used in food seasonings and traditional medicine. 297 mg/kg of DEHT and 48 mg/kg of DEHP were isolated from dried and grounded C. spinosa L. leaves using column chromatography and semi-preparative high-performance liquid chromatography. Our study adds to the increase in the detection of plasticizers in our food and medicinal plants and to the alarming concern about their potential adverse effects on human health.

Hemodynamics and Wall Shear Stress of Blood Vessels in Aortic Coarctation with Computational Fluid Dynamics Simulation.

The purpose of this study was to identify the characteristics of blood flow in aortic coarctation based on stenotic shape structure, stenosis rate, and the distribution of the wall load delivered into the blood vessels and to predict the impact on aneurysm formation and rupture of blood vessels by using a computational fluid dynamics modeling method. It was applied on the blood flow in abdominal aortic blood vessels in which stenosis occurred by using the commercial finite element software ADINA on fluid-solid interactions. The results of modeling, with an increasing stenosis rate and Reynolds number, showed the pressure drop was increased and the velocity was greatly changed. When the stenosis rate was the same, the pressure drop and the velocity change were larger in the stenosis with a symmetric structure than in the stenosis with an asymmetric one. Maximal changes in wall shear stress were observed in the area before stenosis and minimal changes were shown in stenosis areas. The minimal shear stress occurred at different locations depending on the stenosis shape models. With an increasing stenosis rate and Reynolds number, the maximal wall shear stress was increased and the minimal wall shear stress was decreased. Through such studies, it is thought that the characteristics of blood flow in the abdominal aorta where a stenosis is formed will be helpful in understanding the mechanism of growth of atherosclerosis and the occurrence and rupture of the abdominal aortic flow.

Effect of Intersection Angle of Input Channels in Droplet Generators.

In this paper, we studied the effects of the intersection angle between the inlet channels on the droplet diameter using a COMSOL Multiphysics® simulation. We employed the level-set method to study the droplet generation process inside a microfluidic flow device. A flow-focusing geometry was integrated into a microfluidics device and used to study droplet formation in liquid-liquid systems. Droplets formed by this flow-focusing technique are typically smaller than the upstream capillary tube and vary in size with the flow rates. Different intersection angles were modeled with a fixed width of continuous and dispersed channels, orifices, and expansion channels. Numerical simulations were performed using the incompressible Navier-Stokes equations for single-phase flow in various flow-focusing geometries. As a result of modeling, when the dispersed flow rate and the continuous flow rate were increased, the flow of the continuous flow fluid interfered with the flow of the dispersed flow fluid, which resulted in a decrease in the droplet diameter. Variations in the droplet diameter can be used to change the intersection angle and fluid flow rate. In addition, it was predicted that the smallest diameter droplet would be generated when the intersection angle was 90°.

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides.

Herein we report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1-2 hours, which provides an environmentally friendly access to 3,4,5-trisubstituted isoxazoles, an important class of structures found in numerous bioactive natural products and pharmaceuticals. Additionally, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability.

Effects of Molybdenum on Improvement of Anti-Corrosion by Plasma Ion Nitriding for Austenitic Stainless Steels.

Corrosion characteristics of SUS 304 and SUS 316L under the marine environment were investigated by plasma ion nitriding at 450 °C with a gas ratio of 25% N2 and 75% H2 for 10 hours. In the anodic polarization experiment performed in natural seawater, noble pitting potential and wide passive region were exhibited in SUS 316L due to the synergistic effect of molybdenum and nitrogen even after plasma ion nitriding compared with SUS 304. In the corrosion rate obtained by an extrapolation method after plasma ion nitriding, a similar result of corrosion current density represented in SUS 304 while lower corrosion current density was analyzed in SUS 316L.

Evaluation of Durability Depending on Two Step Anodizing Process Time Using Sulfuric Acid Electrolyte.

Naturally grown aluminum oxide film is about 10 nm in thickness, which is extremely thin with low commercial value, so that Al and its alloys are electrochemically treated to form a layer much thicker than the natural one. Such film received attention from academic and industrial for its high hardness and excellent corrosion resistance, which allows it to be colored in the desired shade. However, almost no investigations have been conducted to improve durability with anodizing process application on aluminum vessels so far. In this study, the optimum process time was established by applying anodizing technology to artificially form oxide film with excellent wear resistance on the material surface. The results of the experiments revealed that the quality of oxide film affected the cavitation resistance depending on the different anodizing process times. Consequently, 40 minutes of process time is determined to be the optimum, showing least amount of damage.

Characterization of Cavitation-Erosion Resistance of Plasma Ion Nitrided 316L Stainless Steel Under Shock Wave in Seawater.

In this study, the characteristics of cavitation-erosion resistance of 316L stainless steel after plasma ion nitriding at various temperatures were investigated in natural seawater. Plasma ion nitriding was performed with N2 and H2 at a ratio of 1:4 from 400 to 500 °C for 10 hours. Micro-Vickers hardness measurement showed that the mechanical properties were improved by increasing hardness due to the formation of expanded austenite (S-phase) at 400 °C and 450 °C and γ'-Fe4N and CrN phases at 500 °C. In the cavitation-erosion test, weight loss and damage rate decreased with increasing nitriding temperatures up to 450 °C, while the depth of damage was found to be increased at 500 °C. The lowest weight loss and damage depth were obtained at 450 °C, which measured the thickest layer of γN phase. At 500 °C, cavitation-erosion damage was significantly occurred due to the internal residual stress accumulated during the plasma ion nitriding.

Influence of Sensitization on Mechanical Properties of AISI 304 Stainless Steel under High-Temperature.

This study investigated influence of sensitization on the mechanical properties of AISI 304 stainless steel. The small and tensile specimens were isothermally aged at 650 °C for up to 1000 hours. Microstructure and precipitates of these specimens were characterized by scanning electrode microscope with energy dispersive X-ray spectroscopy. The degree of sensitization of aged specimens was measured by double loop electrochemical potentiodynamic reactivation method. The tensile test was conducted to evaluate mechanical properties of these specimens. With the progress of aging, the degree of sensitization value drastically increased to more than 50% as Cr-rich carbides were precipitated in the austenite grain boundaries. Also, the mechanical properties were degraded, and fracture mode drastically changed from ductile to brittle. As a result, the surface damage and degradation of mechanical properties were correlated with the degree of sensitization value.

Cavitation Damage Characteristics of Shot Peened ALBC3 Alloy.

Copper alloys have widely used for marine plants, ship building equipment, and renewable energy facilities under marine environment due to its excellent castability, durability, and corrosion resistance. In this study, the surface of ALBC3 alloy was modified with shot peening time to improve the strength and cavitation characteristics. For evaluation of cavitation resistance, cavitation experiments for the non-shot peened and shot-peened specimens were performed to investigate the extent of damage and determine the weight loss. As a result, the shot peened ALBC3 alloys improved cavitation resistance. In particular, the shot peening time of 3.5 min was considered to be the optimum shot peening condition since it presented an improvement of 35.7% in cavitation resistance.

Effect of Applied Current Density on Cavitation-Erosion Characteristics for Anodized Al Alloy.

Surface finishing is as important as selection of material to achieve durability. Surface finishing is a process to provide surface with the desired performance and features by applying external forces such as thermal energy or stress. This study investigated the optimum supply current density for preventing from cavitation damages by applying to an anodizing technique that artificially forms on the surface an oxide coating that has excellent mechanical characteristics, such as hardness, wear resistance. Result of hardness test, the greater hardness was associated with greater brittleness, resulting in deleterious characteristics. Consequently, under conditions such as the electrolyte concentration of 10 vol.%, the processing time of 40 min, the electrolyte temperature of 10 °C, and the current density of 20 mA/cm2 were considered to be the optimum anodizing conditions for improvement of durability in seawater.

Cavitation Erosion Behavior of Electroless Ni-P Coating and Optimization of Process Parameter Using Analysis of Variance with Orthogonal Array.

This study investigated the cavitation erosion resistance of electroless Ni-P (EN) coated gray cast iron (GCI) in seawater solution. Furthermore, the optimum coating design parameters were examined to minimize cavitation erosion damage through analysis of variance (ANOVA) based on the L9 orthogonal array. In this study, four coating design factors were used: concentration of source of nickel (A), concentration of reducer agent (B), deposition temperature (C), and pressure of shot peening (D). In accordance with the regulation of the modified ASTM G32, the cavitation erosion experiment was conducted for 1 hour in a seawater solution to find the optimum design parameters which can minimize the cavitation erosion damage. Besides, ANOVA was performed to verify the contribution of each coating design parameter. As a result, the concentration of reducer agent among the EN process parameters was determined as the most significant factor in the cavitation erosion behavior.

Antimycin-type depsipeptides: discovery, biosynthesis, chemical synthesis, and bioactivities.

Covering: up to 2016Antimycin-type depsipeptides are a family of natural products with great structural diversity and outstanding biological activities. These compounds have typically been isolated from actinomycetes and are generated from hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly lines. This review covers the literature on the four classes of antimycin-type depsipeptides, which differ by macrolactone ring size, and it discusses the discovery, biosynthesis, chemical synthesis, and biological activities of this family of compounds.

Electrochemical Corrosion Characteristics of Arc-Ion-Plated AlTiN Coating for Marine Application.

In this study, aluminum titanium nitride (AlTiN) coating was deposited by arc ion plating onto mirror finish STS 304 plate. The surface and cross-section of the coating was characterized by SEM and EDX analysis. Several electrochemical corrosion experiments were performed including rest potential measurement, potentiodynamic polarization experiment and Tafel analysis. The result of the experiments indicated that the AlTiN coating presented lower corrosion current density than the substrate material (STS 304) under uniform corrosion environment. It was also observed that AlTiN coating may have a risk of being attacked by localized corrosion attack such as pitting when pores or micro/nano particles in the coating are exposed to chloride ion containing corrosion environment, especially marine environment.

Determination of sulfuric acid concentration for anti-cavitation characteristics of Al alloy by two step anodizing process to forming nano porous.

Al alloy is a highly active metal but forms a protective oxide film having high corrosion resistance in atmosphere environment. However, the oxide film is not suitable for practical use, since the thickness of the film is not uniform and it is severly altered with formation conditions. This study focused on developing an aluminum anodizing layer having hardness, corrosion resistance and abrasion resistance equivalent to a commercial grade protective layer. Aluminum anodizing layer was produced by two-step aluminum anodizing oxide (AAO) process with different sulfuric acid concentrations, and the cavitation characteristics of the anodized coating layer was investigated. In hardness measurement, the anodized coating layer produced with 15 vol.% of sulfuric acid condition had the highest value of hardness but exhibited poor cavitation resistance due to being more brittle than those with other conditions. The 10 vol.% of sulfuric acid condition was thus considered to be the optimum condition as it had the lowest weight loss and damage depth.

Susceptibility of Escherichia coli from community-acquired urinary tract infection to fosfomycin, nitrofurantoin, and temocillin in Korea.

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Effects of hydrogen permeation on the mechanical characteristics of electroless nickel-plated free-cutting steel for application to the hydrogen valves of hydrogen fuel cell electric vehicles.

Electroless nickel plating is a suitable technology for the hydrogen industry because electroless nickel can be mass-produced at a low cost. Investigating in a complex environment where hydrogen permeation and friction/wear work simultaneously is necessary to apply it to hydrogen valves for hydrogen fuel cell vehicles. In this research, the effects of hydrogen permeation on the mechanical characteristics of electroless nickel-plated free-cutting steel (SUM 24L) were investigated. Due to the inherent characteristics of electroless nickel plating, the damage (cracks and delamination of grain) and micro-particles by hydrogen permeation were clearly observed at the grain boundaries and triple junctions. In particular, the cracks grew from grain boundary toward the intergranualr. This is because the grain boundaries and triple junctions are hydrogen permeation pathways and increasing area of the hydrogen partial pressure. As a result, its surface roughness increased by a maximum of two times, and its hardness and adhesion strength decreased by hydrogen permeation. In particular, hydrogen permeation increased the friction coefficient of the electroless nickel-plated layer, and the damage caused by adhesive wear was significantly greater, increasing the wear depth by up to 5.7 times. This is believed to be due to the decreasing in wear resistance of the electroless nickel plating layer damaged by hydrogen permeation. Nevertheless, the Vickers hardness and the friction coefficient of the electroless nickel plating layer were improved by about 3 and 5.6 times, respectively, compared with those of the free-cutting steel. In particular, the electroless nickel-plated specimens with hydrogen embrittlement exhibited significantly better mechanical characteristics and wear resistance than the free-cutting steel.

Strain-Programmed Adhesive Patch for Accelerated Photodynamic Wound Healing.

As an alternative to tissue adhesives, photochemical tissue bonding is investigated for advanced wound healing. However, these techniques suffer from relatively slow wound healing with bleeding and bacterial infections. Here, the versatile attributes of afterglow luminescent particles (ALPs) embedded in dopamine-modified hyaluronic acid (HA-DOPA) patches for accelerated wound healing are presented. ALPs enhance the viscoelastic properties of the patches, and the photoluminescence and afterglow luminescence of ALPs maximize singlet oxygen generation and collagen fibrillogenesis for effective healing in the infected wounds. The patches are optimized to achieve the strong and rapid adhesion in the wound sites. In addition, the swelling and shrinking properties of adhesive patches contribute to a nonlinear behavior in the wound recovery, playing an important role as a strain-programmed patch. The protective patch prevents secondary infection and skin adhesion, and the patch seamlessly detaches during wound healing, enabling efficient residue clearance. In vitro, in vivo, and ex vivo model tests confirm the biocompatibility, antibacterial effect, hemostatic capability, and collagen restructuring for the accelerated wound healing. Taken together, this research collectively demonstrates the feasibility of HA-DOPA/ALP patches as a versatile and promoting solution for advanced accelerated wound healing, particularly in scenarios involving bleeding and bacterial infections.

The effects of maintaining temperature in annealing heat treatment for an FSWed 6061-T6 Al alloy.

The technological development of all kinds of lightweight transportation devices including vehicles, aircraft, ships, etc. has progressed markedly with the demand for energy saving and environmental protection. Aluminum alloy is in the spotlight as it is a suitable environmentally friendly material. However, deformation is a major problem during the welding process because aluminum alloy has a large thermal expansion coefficient. In addition, it is known that its corrosion resistance is excellent; nevertheless, in practice, considerable corrosion is generated and this is a major problem. To solve this problem, the friction stir welding (FSW) technology is applied extensively at various industrial fields as a new welding technique. This method involves a process in which materials are joined by frictional heat and physical force. Therefore, we evaluated improvements in mechanical properties and corrosion resistance through annealing heat treatment after FSW. The electrochemical experiment did not show a significant difference. However, the microstructure observation showed defectless, fine crystal particles, indicating excellent properties at 200-225°C.

An investigation on the optimum corrosion protection potential for minimization of cavitation damage using the potentiostatic method in seawater.

In this study, we replaced the expensive blade material with an aluminum-bronze alloy that has excellent corrosion resistance and cavitation characteristics and developed the corrosion protection method to improve durability using an electrochemical method. The objective of this study was to identify the electrochemical corrosion protection conditions to minimize cavitation damage due to generating hydrogen gas (2H2O + 2e⁻ → 2OH⁻ + H2) by means of hydrogen overvoltage before the impact pressure of the cavity is transferred to the surface. In the constant potential experiment under the cavitation environment, the energy was reflected or cancelled out by collision of the cavities with the hydrogen gas generated by the hydrogen overvoltage. As a result, the optimal corrosion prevention potential in the dynamic state is assumed to be the range of -1.4 to -1.7 V, which is the range at which active polarization took place.