Transition-metal-free synthesis of 1,4-benzoxazepines via [4+3]-cycloaddition of para-quinone methides with azaoxyallyl cations

A formal[4+3]-cycloaddition reaction of ortho-hydroxyphenyl-substituted para-quinone methides(p-QMs)with in-situ generated azaoxyallyl cations is reported.The reaction occurs under very mild reaction conditions(transition-metal free,room temperature,cheap inorganic base)and provides a very efficient route to a series of biologically important 1,4-benzoxazepine derivatives in good to excellent yields.     

Dielectric Properties Investigation of Metal–Insulator–Metal (MIM) Capacitors

This study presents the construction and dielectric properties investigation of atomic-layer-deposition Al₂O₃/TiO₂/HfO₂ dielectric-film-based metal–insulator–metal (MIM) capacitors. The influence of the dielectric layer material and thickness on the performance of MIM capacitors are also systematically investigated. The morphology and surface roughness of dielectric films for different materials and thicknesses are analyzed via atomic force microscopy (AFM). Among them, the 25 nm Al₂O₃-based dielectric capacitor exhibits superior comprehensive electrical performance, including a high capacitance density of 7.89 fF·µm⁻², desirable breakdown voltage and leakage current of about 12 V and 1.4 × 10⁻¹⁰ A·cm⁻², and quadratic voltage coefficient of 303.6 ppm·V⁻². Simultaneously, the fabricated capacitor indicates desirable stability in terms of frequency and bias voltage (at 1 MHz), with the corresponding slight capacitance density variation of about 0.52 fF·µm⁻² and 0.25 fF·µm⁻². Furthermore, the mechanism of the variation in capacitance density and leakage current might be attributed to the Poole–Frenkel emission and charge-trapping effect of the high-k materials. All these results indicate potential applications in integrated passive devices.     

Euphorbiasteroid Abrogates EGFR and Wnt/β-Catenin Signaling in Non-Small-Cell Lung Cancer Cells to Impart Anticancer Activity

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3β^S9 with a parallel increase in β-TrCP and phosphorylation of GSK-3β^Y216. Lithium chloride treatment increased the phosphorylation of GSK-3β^S9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells.     

DNA Interaction,DNA Photocleavage,Photocytotoxicity In Vitro,and Molecular Docking of Naphthyl-Appended Ruthenium Complexes

With the development of metal-based drugs, Ru(II) compounds present potential applications of PDT (photodynamic therapy) and anticancer reagents. We herein synthesized two naphthyl-appended ruthenium complexes by the combination of the ligand with naphthyl and bipyridyl. The DNA affinities, photocleavage abilities, and photocytotoxicity were studied by various spectral methods, viscosity measurement, theoretical computation method, gel electrophoresis, and MTT method. Two complexes exhibited strong interaction with calf thymus DNA by intercalation. Production of singlet oxygen (¹O₂) led to obvious DNA photocleavage activities of two complexes under 365 nm light. Furthermore, two complexes displayed obvious photocytotoxicity and low dark cytotoxicity towards Hela, A549, and A375 cells.     

An unexpected all-metal aromatic tetranuclear silver cluster in human copper chaperone Atox1

Metal clusters, such as iron–sulfur clusters, play key roles in sustaining life and are intimately involved in the functions of metalloproteins. Herein we report the formation and crystal structure of a planar square tetranuclear silver cluster when silver ions were mixed with human copper chaperone Atox1. Quantum chemical studies reveal that two Ag 5s¹ electrons in the tetranuclear silver cluster fully occupy the one bonding molecular orbital, with the assumption that this Ag₄ cluster is Ag₄²⁺, leading to extensive electron delocalization over the planar square and significant stabilization. This bonding pattern of the tetranuclear silver cluster represents an aromatic all-metal structure that follows a 4n + 2 electron counting rule (n = 0). This is the first time an all-metal aromatic silver cluster was observed in a protein.

Metal clusters, such as iron–sulfur clusters, play key roles in sustaining life and are intimately involved in the functions of metalloproteins.     

EGFAFS: A Novel Feature Selection Algorithm Based on Explosion Gravitation Field Algorithm

Feature selection (FS) is a vital step in data mining and machine learning, especially for analyzing the data in high-dimensional feature space. Gene expression data usually consist of a few samples characterized by high-dimensional feature space. As a result, they are not suitable to be processed by simple methods, such as the filter-based method. In this study, we propose a novel feature selection algorithm based on the Explosion Gravitation Field Algorithm, called EGFAFS. To reduce the dimensions of the feature space to acceptable dimensions, we constructed a recommended feature pool by a series of Random Forests based on the Gini index. Furthermore, by paying more attention to the features in the recommended feature pool, we can find the best subset more efficiently. To verify the performance of EGFAFS for FS, we tested EGFAFS on eight gene expression datasets compared with four heuristic-based FS methods (GA, PSO, SA, and DE) and four other FS methods (Boruta, HSICLasso, DNN-FS, and EGSG). The results show that EGFAFS has better performance for FS on gene expression data in terms of evaluation metrics, having more than the other eight FS algorithms. The genes selected by EGFAGS play an essential role in the differential co-expression network and some biological functions further demonstrate the success of EGFAFS for solving FS problems on gene expression data.     

Effect of Different Processing Methods on the Chemical Constituents of Scrophulariae Radix as Revealed by 2D NMR-Based Metabolomics

Scrophulariae Radix (SR) is one of the oldest and most frequently used Chinese herbs for oriental medicine in China. Before clinical use, the SR should be processed using different methods after harvest, such as steaming, “sweating”, and traditional fire-drying. In order to investigate the difference in chemical constituents using different processing methods, the two-dimensional (2D) ¹H-¹³C heteronuclear single quantum correlation (¹H-¹³C HSQC)-based metabolomics approach was applied to extensively characterize the difference in the chemical components in the extracts of SR processed using different processing methods. In total, 20 compounds were identified as potential chemical markers that changed significantly with different steaming durations. Seven compounds can be used as potential chemical markers to differentiate processing by sweating, hot-air drying, and steaming for 4 h. These findings could elucidate the change of chemical constituents of the processed SR and provide a guide for the processing. In addition, our protocol may represent a general approach to characterizing chemical compounds of traditional Chinese medicine (TCM) and therefore might be considered as a promising approach to exploring the scientific basis of traditional processing of TCM.     

HIGH-FREQUENCY VIBRATIONS OF CORRUGATED CYLINDRICAL PIEZOELECTRIC SHELLS

Coupled extensional and flexural cylindrical vibrations of a corrugated cylindrical piezoelectric shell consisting of multiple pieces of circular cylindrical surfaces smoothly connected along their generatrix are studied. To validate the results for the case of relatively thick shells or equivalently high-frequency modes with short wavelengths, existing analysis is extended by considering shear deformation and rotatory inertia. An analytical solution is obtained. Based on the solution, resonant frequencies and mode shapes are calculated.     

Development of a Quantitative Method for Detection of Multiclass Veterinary Drugs in Feed Using Modified QuPPe Extraction and LC–MS/MS

A method was developed for the rapid and quantitative analysis of 30 veterinary drugs belonging to 17 classes (amphenicols (1), anthelmintics (1), cephalosporins (4), coccidiostats (1), lincosamides (1), macrolide (1), nitroimidazole (1), penicillins (3), phenylhydrazines (1), polypeptides (1), pyrethrins (1), quinolones (5), sulfonamides (3), tetracycline (3), neuroleptic agents (1), triazene trypanocidal agents (1), other. (1)) in feeds. The proposed method with a modified Quick Polar Pesticides (QuPPe) sample preparation was validated for the determination of 30 veterinary drugs in feed samples by liquid chromatography triple-quadrupole mass spectrometry (LC–MS/MS). The sample was extracted with methanol containing 1% acetic acid and purified by dispersive solid-phase extraction (d-SPE) with C18. Good linearity (r² ≥ 0.98) was observed, and the LOQ values ranged from 10 to 200 µg/kg. Average recoveries ranged from 70.8 to 118.4%, and the relative standard deviation was ≤ 18.7%. This validated method was used in the determination of 30 veterinary drugs in 142 feed samples obtained from South Korea. The results show that lincomycin was present in only one of the tested feed samples, although it was detected at a value lower than the LOQ. In conclusion, this multi-residue method can be used for screening through the detection and quantitation of residual multiclass veterinary drugs in feed samples.