Search

In recent years, inflammatory disorders have emerged as a significant concern for human health. Through ongoing research on anti‐inflammatory agents, alpinetin has shown promising anti‐inflammatory properties, including involvement in epigenetic modification pathways. As a crucial regulator of epigenetic modifications, Mecp2 may play a role in modulating the epigenetic effects of alpinetin, potentially impacting its anti‐inflammatory properties. To test this hypothesis, two key components, p65 (a member of NF‐KB family) and p300 (a type of co‐activator), were screened by the expression profiling microarray, which exhibited a strong correlation with the intensity of LPS stimulation in mouse macrophages. Meanwhile, alpinetin demonstrates the anti‐inflammatory properties through its ability to disrupt the synthesis of p65 and its interaction with promoters of inflammatory genes, yet it did not exhibit similar effects on p300. Additionally, Mecp2 can inhibit the binding of p300 by attaching to the methylated inflammatory gene promoter induced by alpinetin, leading to obstacles in promoter acetylation and subsequently impacting the binding of p65, ultimately enhancing the anti‐inflammatory capabilities of alpinetin. Similarly, in a sepsis mouse model, it was observed that homozygotes overexpressing Mecp2 showed a greater reduction in organ damage and improved survival rates compared to heterozygotes when administered by alpinetin. However, blocking the expression of DNA methyltransferase 3A (DNMT3A) resulted in the loss of Mecp2′s anti‐inflammatory assistance. In conclusion, Mecp2 may augment the anti‐inflammatory effects of alpinetin through epigenetic 'crosstalk', highlighting the potential efficacy of a combined therapeutic strategy involving Mecp2 and alpinetin for anti‐inflammatory intervention. [ABSTRACT FROM AUTHOR]

Inclined hole arrays on superalloys have important applications in aeroengines. However, defects occur during fabrication of inclined holes using thermal drilling methods, i.e. electrical discharge drilling (EDD), including a recast layer and microcracks on the hole wall. Therefore, abrasive water flow polishing (AWFP) of a superalloy inclined hole array machined via EDD was investigated in this study. Two types of specimens were designed: a hole array of identical size and a hole array with an identical inclination angle. The fluid simulation revealed that the fluid velocity and pressure on the lower edge of the inclined hole were significantly higher than those on the upper edge when the fluid flowed forward. The fluid characteristics exhibited opposite trends when backward flow was implemented. Time-division bidirectional flow can effectively compensate for flow field nonuniformity and improve material removal consistency during polishing. The experimental results show that for inclined holes with identical inclination angles, the size expansion decreases with an increase in the hole diameter owing to the lower fluid velocity and material removal volume in the relatively larger holes. Consequently, surface roughness Ra increases with hole size. For inclined holes with identical diameters, the size expansions of the entrance and exit approach the same level; whereas, Ra decreased with an increase in the inclination angle. The hole taper slightly reduced in all cases. Using garnet abrasives with 1300 mesh size, 1.5 wt.% abrasive concentration, and 3 MPa fluid pressure, the surface roughness Ra of target holes was reduced from pre-polishing ≥ 5.0 μ m to approximately post-polishing 1.0 μ m. The recast layer on the hole wall caused by EDD was completely removed. [ABSTRACT FROM AUTHOR]