Exploring the molecular mechanism of Epimedium for the treatment of ankylosing spondylitis based on network pharmacology, molecular docking, and molecular dynamics simulations.

Ankylosing spondylitis (AS) is a rheumatic disease that causes inflammation and bone formation in the spine. Despite significant advances in treatment, adverse side effects have triggered research into natural compounds. Epimedium (EP) is a traditional Chinese herb with a variety of pharmacological activities, including antirheumatic, anti-inflammatory, and immunomodulatory activities; however, its direct effects on AS treatment and the underlying molecular mechanisms have not been systematically studied. Thus, here, we used network pharmacology, molecular docking, and molecular dynamics simulations to explore the targets of EP for treating AS. We constructed an interaction network to elucidate the complex relationship between EP and AS. Sixteen active ingredients in EP were screened; 80 potential targets were identified. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone, anhydroicaritin, and luteolin were the core components and TNF, IL-6, IL-1ß, MMP9, and PTGS2 were the core targets. The GO and KEGG analyses indicated that EP may modulate multiple biological processes and pathways, including the AGE-RAGE, TNF, NF-κB/MAPK, and TLR signaling pathways, for AS treatment. Molecular docking and molecular dynamics simulations showed good affinity between the active components and core targets of EP, with stable binding within 100 nanoseconds. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone possessed the highest free energy of binding to PTGS2 and TNF (-115.575 and - 87.676 kcal/mol, respectively). Thus, EP may affect AS through multiple pathways, including the alleviation of inflammation, oxidative stress, and immune responses. In summary, we identified the active components and potential targets of EP, highlighting new strategies for the further experimental validation and exploration of lead compounds for treating AS.

Strain Rate Dependence and Recrystallization Modeling for TC18 Alloy during Post-Deformation Annealing.

In this paper, the dependence of dynamic recrystallization (DRX) and post-dynamic recrystallization (PDRX) of TC18 alloy on strain rate within the range of 0.001 s-1~1 s-1 was investigated through isothermal compression and subsequent annealing in the single-phase region. Electron backscatter diffraction (EBSD) characterization was employed to quantify microstructure evolution and to reveal the recrystallization mechanism. At the thermo-deformation stage, the DRX fraction does not exceed 10% at different strain rates, due to the high stacking fault energy of the ß phase. During the subsequent annealing process, the total recrystallization fraction increases from 10.5% to 79.6% with the strain rate increasing from 0.001 s-1 to 1 s-1. The variations in the geometrically necessary dislocation (GND) density before and after annealing exhibit a significant discrepancy with the increasing strain rate, indicating that the GND density is a key factor affecting the PDRX rate. The PDRX mechanisms, namely meta-dynamic recrystallization (MDRX), continuous static recrystallization (CSRX) and discontinuous static recrystallization (DSRX), were also revealed during the annealing process. A new kinetic model coupling DRX and PDRX was proposed to further describe the correlation between recrystallization and the strain rate during continuous deformation and annealing. This new model facilitates the prediction of recrystallization fraction during isothermal deformation and annealing of titanium alloys.