Modafinil (MOD) is a nootropic nonamphetamine medication of growing therapeutic interest. Despite the drug's rapidly expanding usage, little is known about its toxic effects on male reproduction. The present study aimed to reveal the dose-dependent MOD-induced reproductive toxicity and the potential mitigating effects of selenium (Se) in testis. Adult male rats were administered MOD300 or 600 mg/kg/day alone for 14 days or co-treated with Se either 0.1 or 0.2 mg/kg/day for 21 days. Functional, biochemical (Testosterone, Follicle-stimulating hormone, Luteinizing hormone, Nitric oxide, Malondialdehyde, Superoxide Dismutase, and Total Antioxidant Capacity), molecular, histopathological, and Transmission electron microscopy examinations were studied. Results revealed that MOD doses significantly induced deterioration of erectile function and sperm quality accompanied by a significant alteration in reproductive hormonal levels (Total and Free testosterone, LH, and FSH). MOD doses also evoked a significant increase in MDA, and NO, with a significant decrease in SOD and TAC. Furthermore, upregulation of the PI3K/Akt/NF-ҡB pathway and the increased expression of the inflammatory gene (iNOS) were demonstrated with both MOD doses. Molecular docking highlighted the virtual mechanism of binding of MOD towards the tested proteins. The observed toxicity was further confirmed by the histopathological and ultrastructural changes. The results demonstrated a significant improvement in the parameters when a Se dose of 0.2 mg/kg/day was co-administered. In conclusion, MOD interferes with male reproductive function in a dose-dependent manner, and Se may be a potentially helpful new approach for abating such toxicity.

This paper presents an adaptive fixed-time fault-tolerant control scheme for nonstrict-feedback nonlinear systems subject to actuator faults, input saturation, and external disturbances. Radial basis function neural networks approximate unknown nonlinear functions within the system. To address the complexity typically associated with the traditional backstepping design, command filtering is introduced, significantly simplifying the control development process. An error compensation technique is further incorporated to reduce the impact of filtering-induced errors on system performance. To effectively handle input saturation, a smooth non-affine approximation is utilized to represent the saturation behavior. The proposed controller is developed using Lyapunov-based analysis and backstepping design, ensuring both transient and steady-state tracking objectives are met. A funnel constraint mechanism is integrated to maintain the tracking error within predefined performance bounds. Theoretical analysis confirms the fixed-time stability of the closed-loop system, and simulation examples are provided to demonstrate the effectiveness and feasibility of the proposed approach.

Chitosan, a natural biological macromolecule, was employed to coat boswellic acids extract nanoparticles (CT/BA NPs) to enhance their gastroprotective potential. This study evaluated the therapeutic effects of CT/BA NPs compared to free boswellic acids (BA) in a murine model of ethanol-induced gastric ulcers. Histological analysis showed that CT/BA NPs preserved gastric gland integrity and minimized inflammatory infiltration, achieving a ~ 97% reduction in ulcer index compared to the ulcer group, whereas BA alone achieved ~ 80% protection. CT/BA NPs treatment markedly modulated key growth factors, with TGF-α and TGF-β1 increased by more than 100% relative to the ulcer group, while VEGF expression was suppressed by ~ 74%, indicating more controlled angiogenesis. In addition, CT/BA NPs significantly reduced RAS and ERK levels (by ~ 1.6- and 1.2-fold, respectively) and lowered TNF-α compared to BA, highlighting their role in regulating the RAS-ERK signaling pathway. The superior mucoadhesive properties of CT/BA NPs (76.4% vs. 15.8% for BA NPs) improved gastric mucosal retention, contributing to localized therapeutic effects. Collectively, these findings demonstrate that CT/BA NPs provide promising gastroprotection by promoting epithelial healing, modulating growth factors and signaling pathways, and mitigating ulcer severity.