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Glioblastoma (GBM) is known for its aggressive nature and poor prognosis, with currently no effective treatment available. Research has shown that introducing fluorinated functional groups into different parts of natural product quinoline significantly affects its anti-tumor activity. Therefore, this study synthesized the trifluoromethyl quinoline derivative FKL296 to investigate its anti-tumor effect on GBM and reveal its mechanism of action. In vitro and in vivo studies have shown that FKL296 effectively inhibitd the growth of GBM and is relatively safe and low toxicity, whice also induced cell apoptosis and autophagy. Additionally, protein kinase profiling and molecular docking analyses have revealed a strong binding affinity between FKL296 and SGK1. Cellular thermal shift assay experiments have confirmed the targeting of SGK1 by FKL296 and its role in enhancing SGK1 stability. Bioinformatics analysis and pathway validation indicated that FKL296 targeted SGK1 and inhibited autophagy in tumor cells through the mTOR/FOXO3a signaling pathway. In summary, FKL296 may become a promising drug for the treatment of GBM.

Simple Summary: Antibiotic growth promoters are encountering diminishing social acceptance due to escalating public concern regarding the potential risks of drug residues to human health. Traditional Chinese medicine (TCM), with its extensive history of use for human health, has been validated as safe and effective through numerous clinical practices. TCM encompasses a wide range of natural herbs and plants that are used to treat or prevent diseases or promote health. The natural constituents of TCM minimize the risk of drug residue accumulation, making it a potential alternative to antibiotics in livestock feed. The present study introduced a TCM extract as a potential substitute for antibiotics that could improve feed efficiency and alter nutrient metabolism in sheep. The findings offer significant data for advancing research into TCM's application in boosting ruminant productivity. Traditional Chinese medicine (TCM) encompasses a wide range of natural herbs and plants that are used to treat or prevent diseases or promote health. This study aimed to evaluate the effect of feeding a TCM formula extract on nitrogen (N) balance, microbial nitrogen supply (MNS), and plasma leucine kinetics in sheep. Six sheep were fed with mixed hay (Hay-diet) only or supplemented with 2% TCM (mixture of Astragalus root, Angelica root, and Atractylodes rhizome; TCM-diet) in a crossover design over two 21-day periods. An isotope dilution of [1-13C]leucine was used to measure the rate of plasma leucine turnover. Purine derivative (PD) excretion in urine was determined to estimate the MNS. The TCM-diet significantly increased N intake (p < 0.01) and N digestibility (p = 0.02) compared to the Hay-diet, with less N excretion (p = 0.02) in feces, while no significant difference was observed between diets in terms of N excretion in urine and N retention. Total PD excretion and MNS were higher (p < 0.01), as well as the turnover rate of plasma leucine tended to be higher (p = 0.06) with the supplementation of TCM. The present results suggested that the TCM formula could be considered as a potential feed additive for ruminant production. [ABSTRACT FROM AUTHOR]

The composite bonded-bolted hybrid joint (BBHJ) is widely focused and developed in aerospace and aviation fields for its full consideration of advantages of bolt and bonded joint. In this review, the relative research development of this BBHJ in composite structures at home and abroad is thoroughly summarized. Focusing on enhancing load sharing and structure bearing ability, the research status, research development and related achievements are introduced from the aspects of composite repairing and damage tolerance, forming process and force-transferring route, parametric influence and load sharing, adhesive de-bonding inhibition and multi-bolt load sharing, and the bearing strength prediction. The existing problems, probable solutions and future developing direction of this joint style is further discussed in order to provide useful reference for the further application of BBHJ in composite structure.

As a synthetic functional analog of salicylic acid, 2,6-dichloroisonicotinic acid (INA) is effective in inducing the host disease resistance of a plant against a pathogen. The effects of INA on controlling postharvest blue and green molds and anthracnose decay and defense-related enzymes on citrus fruits were investigated, and the ascorbic acid of naturally infected citrus flavedo was also measured. Results showed that 1.0 mmol L−1 INA treatments significantly reduced blue and green molds and anthracnose decay development on both wound-inoculated fruit and naturally-infected fruit compared with the control fruit. The treatment effectively enhanced the β-1,3-glucanase (GLU), chitinase (CHI), phenylalanine ammonia-lyase (PAL) and peroxidase (POD) activities and the polyphenol oxidase (PPO) in flavedo. The results presented here suggest that INA might be used as a chemical fungicide substitution to control postharvest diseases in citrus fruits.

Background Epimedium is a famous medicinal plant in China, Southeast Asian and some other regions. Flavonoids are regarded as its supremely important active constituents used in phytomedicines and/or functional foods. It is of theoretical and applied significance to optimize the procedure for extraction of flavonoids with high bioactivity from Epimedium, to unveil extraction mechanism, to identify chemical composition of flavonoids, to analyze free radical-scavenging ability of flavonoids, and to investigate their effects on the model organism Drosophila melanogaster. Methods Box-Behnken design was applied to optimization of extraction procedure. Laser diffraction particle size analysis was used to clarify extraction mechanism. Chemical composition of flavonoids was analyzed using high-performance liquid chromatography. Antiradical capacities of flavonoids were determined by chemical-based assay. Then, effects of flavonoids on catalase (CAT) and glutathione peroxidase (GSH-Px) in D. melanogaster were investigated for the first time. Results The optimal condition for ultrasonic extraction of antioxidant flavonoids from Epimedium pubescens was achieved and extraction mechanism was discussed. Epimedium flavonoids contained icariin, epimedin A, epimedin B and epimedin C. Epimedium flavonoids exhibited the ability to scavenge ABTS+ and DPPH⋅ radicals with EC50 values of 55.8 and 52.1 µg/ml, respectively. Moreover, Epimedium flavonoids were able to increase activities of CAT and GSH-Px in D. melanogaster. For females, oral administration of flavonoids improved CAT and GSH-Px activities by 13.58% and 5.18%, respectively. For males, oral administration of flavonoids increased CAT and GSH-Px activities by 13.90% and 5.65%, respectively. Conclusion Flavonoids ultrasonically extracted from E. pubescens considerably affected antioxidant defense system in D. melanogaster. Flavonoids of E. pubescens showed great potential for becoming a natural antioxidant because of their antiradical ability and effects on CAT and GSH-Px of the model organism.

Four complexes, [Cu4L2(OCH3)2(CH3OH)2]·2H2O (1), [Zn2L2Cl4]·2H2O·2CH3OH (2), [Hg2L2Br4]·4CH3OH (3), and {[CdL2Cl2]·4H2O·4CH3OH}n (4), have been synthesized and characterized from a bis(pyridylhydrazone) ligand (L) with copper(II), zinc(II), mercury(II) or cadmium(II), respectively. Complex 1 exists as a centrosymmetric tetranuclear dimer with L as deprotonated tridentate ligand. Complexes 2 and 3 exist as centrosymmetric metallamacrocycles with L as bidentate ligand. Complex 4 exists as a 1D looped-chain coordination polymer. The thermal stabilities and vapor adsorption properties of the four complexes were investigated as well.

In the title compound, C17H12O4, there is an intramolecular O—H...O hydrogen bond. The dihedral angle between the indane ring system [maximun deviation = 0.023 (2) Å] and the benzene ring is 37.42 (9)°.