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Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive degenerative disease of skeletal muscle, characterized by intramuscular inflammation, muscle regeneration disorder and replacement of muscle with fibroadipose tissue. DMD is caused by the absence of normal dystrophy. Impaired self-renew ability and limited differentiation capacity of satellite cells are proved as main reasons for muscle regeneration failure. The deficiency of estrogen impedes the process of muscle regeneration. However, the role of estrogen receptor β (ERβ) in muscle regeneration is still unclear. This study aims to investigate the role and the pharmacological effect of ERβ activation on muscle regeneration in mdx mice. This study showed that mRNA levels of ERβ and myogenic-related genes both witnessed increasing trends in dystrophic context. Our results revealed that treatment with selective ERβ agonist (DPN, diarylpropionitrile) significantly increased myogenic differentiation 1 (MyoD-1) level and promoted muscle regeneration in mdx mice. Similarly, in mdx mice with muscle-specific estrogen receptor α (ERα) ablation, DPN treatment still promoted muscle regeneration. Moreover, we demonstrated that myoblasts differentiation was accompanied by raised nuclear accumulation of ERβ. DPN treatment augmented the nuclear accumulation of ERβ and, thus, contributed to myotubes formation. One important finding was that forkhead box O3A (FOXO3A), as a pivotal transcription factor in Myod-1 transcription, participated in the ERβ-promoted muscle regeneration. Overall, we offered an interesting explanation about the crucial role of ERβ during myogenesis.

Abstract Background Chronic lymphocytic leukemia (CLL) is one of the most frequent occurring types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. At present, the molecular mechanism driving the pathogenesis and progression of CLL is not fully understood. The protein Synaptotagmin 7 (SYT7) encoded by the SYT7 gene has been found to be closely related to the development of various solid tumors, but its role in CLL is unclear. In this study, we investigated the function and molecular mechanism of SYT7 in CLL. Methods The expression level of SYT7 in CLL was determined by immunohistochemical staining and qPCR. The role of SYT7 in promoting CLL development was verified by in vivo and in vitro experiments. The molecular mechanism of SYT7 in CLL was elucidated by methods such as GeneChip analysis and Co-immunoprecipitation assay. Results Malignant behaviors such as proliferation, migration, and anti-apoptosis of CLL cells were significantly inhibited after SYT7 gene knockdown. In contrast, SYT7 overexpression promoted CLL development in vitro. Consistently, the knockdown of SYT7 also inhibited xenograft tumor growth of CLL cells. Mechanistically, SYT7 promoted CLL development by inhibiting SYVN1-mediated KNTC1 ubiquitination. The KNTC1 knockdown also attenuated the effects of SYT7 overexpression on development of CLL. Conclusions SYT7 regulates the progression of CLL through SYVN1-mediated KNTC1 ubiquitination, which has potential value for molecular targeted therapy of CLL.

The side pile is a crucial mechanical component in station construction using the PBA (pile-beam-arch) method, and its stability during the construction process cannot be overstated. The mechanical differences between single-row and double-row side piles in this construction method have garnered significant attention, yet few studies have been conducted on this matter. Therefore, this paper employs numerical simulation to compare the deformation and mechanical properties of single-row and double-row side piles (the adopted pile type is micro steel pipe pile, abbreviated as MSPP) in a metro station using the PBA method. The findings are validated through the model experiment. It is found that the soil arch effect created by the front-row pile of the double-row piles serves as the primary lining, offering a certain shielding effect to the soil stress behind the back-row pile. Notably, the soil stress values in double-row pile conditions are slightly higher compared to single-row pile condition, leading to a noticeably smaller final deformation of the pile top. The combined bending moments and axial forces of the front-row and back-row piles in double-row piles exceed those of a single-row pile. Specifically, bending moments are highest in single-row piles, followed by front-row piles and then back-row piles, while axial forces are highest in single-row piles, followed by back-row piles and then front-row piles. This suggests that the bending moments and axial forces of double-row piles are smaller than those of a single-row pile. The internal force distribution within the double-row pile is more balanced, thereby enhancing the lining strength and improving the station’s safety through the PBA method. The findings in this paper can serve as valuable references for the design and construction of similar projects.

The side pile is a crucial mechanical component in station construction using the PBA (pile-beam-arch) method, and its stability during the construction process cannot be overstated. The mechanical differences between single-row and double-row side piles in this construction method have garnered significant attention, yet few studies have been conducted on this matter. Therefore, this paper employs numerical simulation to compare the deformation and mechanical properties of single-row and double-row side piles (the adopted pile type is micro steel pipe pile, abbreviated as MSPP) in a metro station using the PBA method. The findings are validated through the model experiment. It is found that the soil arch effect created by the front-row pile of the double-row piles serves as the primary lining, offering a certain shielding effect to the soil stress behind the back-row pile. Notably, the soil stress values in double-row pile conditions are slightly higher compared to single-row pile condition, leading to a noticeably smaller final deformation of the pile top. The combined bending moments and axial forces of the front-row and back-row piles in double-row piles exceed those of a single-row pile. Specifically, bending moments are highest in single-row piles, followed by front-row piles and then back-row piles, while axial forces are highest in single-row piles, followed by back-row piles and then front-row piles. This suggests that the bending moments and axial forces of double-row piles are smaller than those of a single-row pile. The internal force distribution within the double-row pile is more balanced, thereby enhancing the lining strength and improving the station's safety through the PBA method. The findings in this paper can serve as valuable references for the design and construction of similar projects. [ABSTRACT FROM AUTHOR]