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.     

Charge‐Induced Unzipping of Isolated Proteins to a Defined Secondary Structure

Here we present a combined experimental and theoretical study on the secondary structure of isolated proteins as a function of charge state. In infrared spectra of the proteins ubiquitin and cytochrome c, amide I (C=O stretch) and amide II (N–H bend) bands can be found at positions that are typical for condensed‐phase proteins. For high charge states a new band appears, substantially red‐shifted from the amide II band observed at lower charge states. The observations are interpreted in terms of Coulomb‐driven transitions in secondary structures from mostly helical to extended C₅‐type hydrogen‐bonded structures. Support for this interpretation comes from simple energy considerations as well as from quantum chemical calculations on model peptides. This transition in secondary structure is most likely universal for isolated proteins that occur in mass spectrometric experiments.     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

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.     

Analysis of creep due to grain-boundary diffusion in hexagonal microstructures

For steady-state deformation caused by grain-boundary diffusion in hexagonal microstructures, the stress distribution on grain boundaries and the macroscopic strain rates are analysed by taking the effects of viscous grain-boundary sliding into account. The maximum normal stress and the extent of stress concentration are shown to decrease as the grain-boundary viscosity increases. For infinite viscosity and/or extremely small grain sizes, the distribution of the normal stress becomes uniform on grain boundaries. The strain rates are predicted by both the stress analysis and the energy balance method, and the two strain rates are consistent with each other. The predicted strain rates also decrease as the grain-boundary viscosity increases. The present analysis reveals that the grain-size exponent is dependent on the grain size and the grain-boundary viscosity: the exponent becomes unity for small grain sizes and/or high viscosity, while it is three for large grain sizes and/or low viscosity. Recent experimental observations that the strain rates of nano-sized grain are much lower than those predicted by grain-boundary diffusion are explained by the increasing contribution of viscous grain-boundary sliding with decreasing grain size.     

Novel fabrication route for carbon-free and dense CuInSe2 (CIS) thin films via a non-vacuum process for solar cell application

Carbon-free CuInSe₂ (CIS) thin film with a dense microstructure has been prepared using a novel non-vacuum based fabrication route. Cu_xS_y and In₂Se₃ binary nanoparticles, approximately 10 nm in size, were synthesized by a low temperature colloidal process. The precursor film was deposited using the coating ink formulated with the binary nanoparticles and pyridine, and then annealed in the rapid thermal annealing (RTA) chamber at 540 °C for 15 min under selenium (Se) atmosphere. Scanning electron micrographs, X-ray diffraction patterns and Raman spectra showed a phase pure carbon-free and dense CIS thin film was prepared in this method. A solar cell device fabricated using this CIS thin film showed the following photovoltaic characteristics: V_OC = 350 mV, J_SC = 24.72 mA cm⁻², FF = 38.73% and η = 3.36% under standard AM 1.5 condition.     

Machine learning identification of symmetrized base states of Rydberg atoms

Studying the complex quantum dynamics of interacting many-body systems is one of the most challenging areas in modern physics. Here, we use machine learning (ML) models to identify the symmetrized base states of interacting Rydberg atoms of various atom numbers (up to six) and geometric configurations. To obtain the data set for training the ML classifiers, we generate Rydberg excitation probability profiles that simulate experimental data by utilizing Lindblad equations that incorporate laser intensities and phase noise. Then, we classify the data sets using support vector machines (SVMs) and random forest classifiers (RFCs). With these ML models, we achieve high accuracy of up to 100% for data sets containing only a few hundred samples, especially for the closed atom configurations such as the pentagonal (five atoms) and hexagonal (six atoms) systems. The results demonstrate that computationally cost-effective ML models can be used in the identification of Rydberg atom configurations.     

Design,Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA1 and hA3 Adenosine Receptor

Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they induce tumor proliferation and suppress immune cell function. There are four types of human adenosine receptor (hARs): hA₁, hA_2A, hA_2B, and hA₃. Both hA₁ and hA₃ AR play an important role in tumor proliferation. We designed and synthesized novel 1,3,5-triazine derivatives through amination and Suzuki coupling, and evaluated them for binding affinities to each hAR subtype. Compounds 9a and 11b showed good binding affinity to both hA₁ and hA₃ AR, while 9c showed the highest binding affinity to hA₁ AR. In this study, we discovered that 9c inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that 9c caused an increase in intracellular reactive oxygen species (ROS) and a depolarization of the mitochondrial membrane potential. The binding mode of 1,3,5-triazine derivatives to hA₁ and hA₃ AR were predicted by a molecular docking study.