Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F

Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possible mechanism behind the impact of GTW on spermatogenesis, we administered 4 groups of 4-week-old male mice with different doses of GTW. We found a dose-dependent decrease in the number of germ cells after 40 days of GTW treatment, and an increase in apoptotic cells from the low-dose to the high-dose group. During this same period the dimethylated level of histone H3 lysine 9 (H3K9me2) in GTW-treated testes germ cells declined. Additionally, spermatogonial stem cells (SSCs) from 6-day-old mice were isolated to evaluate the possible effect of GTW or triptolide on development of SSCs. We found a significantly higher incidence of apoptosis and lower dimethylation level of H3K9me2 in the SSCs of GTW or triptolide treatment than in controls. Thus, these data suggest that the GTW-induced apoptosis might be responsible for the fertility impairment in mice. This damage could be traced back to the early stages of spermatogenesis. GTW also affected the epigenetic modification of H3K9 in spermatogenesis. Molecular dynamics simulation suggested that triptolide and dimethylated or trimethylated H3K9 might have similar interaction mechanisms with EED (embryonic ectoderm development). These candidate activation mechanisms provide the first glimpse into the pathway of GTW-induced gonad toxicity, which is crucial for further research and clinical application

Modeling Flaw Pulse-Echo Signals in Cylindrical Components Using an Ultrasonic Line-Focused Transducer with Consideration of Wave Mode Conversion

Investigations on flaw responses can benefit the nondestructive testing of cylinders using line-focused transducers. In this work, the system function, the wave beam model, and a flaw scattering model are combined to develop an ultrasonic measurement model for line-focused transducers to predict flaw responses in cylindrical components. The system function is characterized using reference signals by developing an acoustic transfer function for line-focused transducers, which works at different distances for both planar and curved surfaces. The wave beams in cylindrical components are modeled using a multi-Gaussian beam model, where the effects of wave mode conversion and curvatures of cylinders are considered. Simulation results of wave beams are provided to analyze their propagation behaviors. The proposed ultrasonic measurement model is certified from good agreement between the experimental and predicted signals of side-drilled holes. This work provides guidance for evaluating the detection ability of line-focused transducers in cylindrical component testing applications