Solid-state structures of sym-dibenzo-16-crown-5 and its derivatives

Solid-state structures of sym-dibenzo-16-crown-5 (1) and five derivatives with one or two substituents on the three-carbon bridge have been determined. The derivatives with three sp³-hybridized carbons include sym-(propyl)dibenzo-16-crown-5 (4), sym-(pentafluorophenoxy)-dibenzo-16-crown-5 (5), and sym-[di(methoxymethyl)]dibenzo-16-crown-5 (6). Structures of two derivatives with sp²-hybridization of the central carbon (7 and 8) were also determined. Twisting of the three-carbon bridge causes one of the terminal methylene groups to be oriented within the polyether cavity.     

Light‐Regulated Tetracycline Binding to the Tet Repressor

Elucidation of the signal‐transmission pathways between distant sites within proteins is of great importance in medical and bioengineering sciences. The use of optical methods to redesign protein functions is emerging as a general approach for the control of biological systems with high spatiotemporal precision. Here we report the detailed thermodynamic and kinetic characterization of novel chimeric light‐regulated Tet repressor (TetR) switches in which light modulates the TetR function. Light absorbed by flavin mononucleotide (FMN) generates a signal that is transmitted to As‐LOV and YtvA‐LOV fused TetR proteins (LOV=light–oxygen–voltage), in which it alters the binding to tetracycline, the TetR ligand. The engineering of light‐sensing protein modules with TetR is a valuable tool that deepens our understanding of the mechanism of signal transmission within proteins. In addition, the light‐regulated changes of drug binding that we describe here suggest that engineered light‐sensitive proteins may be used for the development of novel therapeutic strategies.     

Simultaneous determination of trifolirhizin, (–)‐maackiain, (–)‐sophoranone,and 2‐(2,4‐dihydroxyphenyl)‐5,6‐methylenedioxybenzofuran from Sophora tonkinensis in rat plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

A new liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of trifolirhizin, (–)‐maackiain, (–)‐sophoranone, and 2‐(2,4‐dihydroxyphenyl)‐5,6‐methylenedioxybenzofuran from Sophora tonkinensis in rat plasma using chlorpropamide as an internal standard. Plasma samples (50 μL) were prepared using a simple deproteinization procedure with 150 μL of acetonitrile containing 100 ng/mL of chlorpropamide. Chromatographic separation was carried out on an Acclaim RSLC120 C₁₈ column (2.1 × 100 mm, 2.2 μm) using a gradient elution consisting of 7.5 mM ammonium acetate and acetonitrile containing 0.1% formic acid (0.4 mL/min flow rate, 7.0 min total run time). The detection and quantitation of all analytes were performed in selected reaction monitoring mode under both positive and negative electrospray ionization. This assay was linear over concentration ranges of 50–5000 ng/mL (trifolirhizin), 25–2500 ng/mL ((–)‐maackiain), 5–250 ng/mL ((–)‐sophoranone), and 1–250 ng/mL 2‐(2,4‐dihydroxyphenyl)‐5,6‐methylenedioxybenzofuran) with a lower limit of quantification of 50, 25, 5, and 1 ng/mL for trifolirhizin, (–)‐maackiain, (–)‐sophoranone, and 2‐(2,4‐dihydroxyphenyl)‐5,6‐methylenedioxybenzofuran, respectively. All the validation data, including the specificity, precision, accuracy, recovery, and stability conformed to the acceptance requirements. The results indicated that the developed method is sufficiently reliable for the pharmacokinetic study of the analytes following oral administration of Sophora tonkinensis extract in rats.     

Novel Reductive Cleavage Reaction of Thiobenzoates with Samarium Diiodide: Convenient Synthesis of Disulfides

The reductive cleavage of thiobenzoates promoted by samarium diiodide afforded various kinds of disulfides in good yields under mild and neutral conditions.     

Study on the Alkylation and Sulfonylation of 3-Aryl-1-methyl-1,2,4-triazolin-5-ones

The alkylation and sulfonylation of 3-aryl-1-methyl-1,2,4-triazolin-5-ones (1) were studied with various alkyl halides and sulfonyl chlorides. The alkylation of 1 with methyl iodide and ethyl bromide afforded N-alkylated products, however with methyl 2-bromopropionate afforded O-alkylated products predominantly. The sulfonylation by methanesulfonyl chloride afforded a mixture of N-sulfonylated and O-sulfonylated products, while the sulfonylation by p-toluenesulfonyl chloride afforded mainly O-sulfonylated products.     

Emergent dynamics of the first‐order stochastic Cucker‐Smale model and application to finance

In this paper, we study stochastic aggregation properties of the financial model for the N‐asset price process whose dynamics is modeled by the weakly geometric Brownian motions with stochastic drifts. For the temporal evolution of stochastic components of drift coefficients, we employ a stochastic first‐order Cucker‐Smale model with additive noises. The asset price processes are weakly interacting via the stochastic components of drift coefficients. For the aggregation estimates, we use the macro‐micro decomposition of the fluctuations around the average process and show that the fluctuations around the average value satisfies a practical aggregation estimate over a time‐independent symmetric network topology so that we can control the differences of drift coefficients by tuning the coupling strength. We provide numerical examples and compare them with our analytical results. We also discuss some financial implications of our proposed model.     

Effects of Induced Exosomes from Endometrial Cancer Cells on Tumor Activity in the Presence of Aurea helianthus Extract

Endometrial cancer (EC) cells metastasize to various regions, including the ovaries, fallopian tubes, cervix, blood, liver, bone, and brain. Various carcinogens are known to cause EC. Exosomes are released from several types of cells and contain various cellular components. In this study, flow cytometry and quantitative PCR were used to evaluate marker levels, cell migration, cell invasion, and mitochondrial membrane potential, and cellular senescence tests were used to estimate cancer activity. The microRNAs were profiled using next-generation sequencing. Although tocopherol-α and rutin content in Aurea helianthus is high, A. helianthus extract was more useful in modulating tumor activity compared to the two aforementioned substances. Notably, we established that the extract induced bioactive exosomes in EC cells, and profiling of miRNAs in the extract-inducing exosomes (EIE) indicated their potency to be developed as a biological drug. The extract and EIE contributed to the following five biological process categories for EC cells: (1) cell migration and invasion suppression, (2) cellular senescence activation by attenuating mitochondrial membrane potential and enhancing autophagy, (3) reproductive cancer activity attenuation, (4) drug susceptibility activation, and (5) EIE containing miRNAs associated with decreasing inflammation.     

High-efficiency organic solar cells enabled by an alcohol-washable solid additive

The solvent additive strategy has been widely utilized to boost the power conversion efficiency (PCE) of organic solar cells(OSCs).However,the residual solvent ...     

Cu(ii)-BODIPY photosensitizer for CAIX overexpressed cancer stem cell therapy

Chemoresistance originating from cancer stem cells (CSCs) is a major cause of cancer treatment failure and highlights the need to develop CSC-targeting therapies. Although enormous progress in both photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been made in recent decades, the efficacy of these modalities against CSC remains limited. Here, we report a new generation photosensitizer, CA9-BPS-Cu(ii), a system that combines three subunits within a single molecule, namely a copper catalyst for CDT, a boron dipyrromethene photosensitizer for PDT, and acetazolamide for CSC targeting via carbonic anhydrase-9 (CA9) binding. A therapeutic effect in MDA-MB-231 cells was observed that is ascribed to elevated oxidative stress mediated by a combined CDT/PDT effect, as well as through copper-catalysed glutathione oxidation. The CSC targeting ability of CA9-BPS-Cu(ii) was evident from the enhanced affinity of CA9-BPS-Cu(ii) towards CD133-positive MDA-MB-231 cells where CA9 is overexpressed vs. CD133-negative cells. Moreover, the efficacy of CA9-BPS-Cu(ii) was successfully demonstrated in a xenograft mouse tumour model.

Chemoresistance originating from cancer stem cells (CSCs) is a major cause of cancer treatment failure and highlights the need to develop CSC-targeting therapies.     

Tomographic imaging of incipient dental-caries using optical coherence tomography and comparison with various modalities

We present the optical coherence tomography (OCT) made to investigate the early dental caries in human teeth and compare its results with those taken by conventional imaging modalities including light illuminating examination (LIE), digital intra-oral radiography (DIOR), and electron probe micro analyzer (EPMA). Morphological features and caries-involved areas of the dental structure were mainly investigated by LIE, DIOR, and OCT to study the infection of the caries lesion in pits and fissures. The biochemical information acquired with EPMA and the morphological features taken with OCT in the early stage of caries were compared and analyzed to present an objective and practical index for the degree of caries. The experimental results allow us to conclude that OCT could be used to provide quantitative analysis of caries based on the reflectivity difference in the specimen.