No abstract

Background Dysregulation of the epitranscriptome causes abnormal expression of oncogenes in the tumorigenic process. Previous studies have shown that NAT10 can regulate mRNA translation efficiency through RNA acetylation. However, the role of NAT10‐mediated acetylation modification in bladder cancer remains elusive. Methods The clinical value of NAT10 was estimated according to NAT10 expression pattern based on TCGA data set and the tumor tissue array. Acetylated RNA immunoprecipitation sequencing was utilized to explore the role of NAT10 in mRNA ac4C modification. Translation efficiency and mRNA stability assay were applied to study the effect of NAT10‐deletion on target genes. The nude mouse model and genetically engineered mice were conducted to further verify the characteristics of NAT10 in promoting BLCA progression and regulating downstream targets. Results NAT10 was essential for the proliferation, migration, invasion, survival and the stem‐cell‐like properties of bladder cancer cell lines. NAT10 was responsible for mRNA ac4C modification in BLCA cells, including BCL9L, SOX4 and AKT1. Deficient NAT10 in both xenograft and transgenic mouse models of bladder cancer reduced the tumor burden. Furthermore, acetylated RNA immunoprecipitation sequencing data and RNA immunoprecipitation qPCR results revealed that NAT10 is responsible for a set of ac4C mRNA modifications in bladder cancer cells. Inhibition of NAT10 led to a loss of ac4C peaks in these transcripts and represses the mRNA's stability and protein expression. Mechanistically, the ac4C reduction modification in specific regions of mRNAs resulting from NAT10 downregulation impaired the translation efficiency of BCL9L, SOX4 and AKT1 as well as the stability of BCL9L, SOX4. Conclusions In summary, these findings provide new insights into the dynamic characteristics of mRNA's post‐transcriptional modification via NAT10‐dependent acetylation and predict a role for NAT10 as a therapeutic target in bladder cancer. Highlights NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumourigenic properties. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1. NAT10 may serve as an effective and novel therapeutic target for BLCA.

In this paper, we present a novel vibration-based piezoelectric energy harvester, capable of collecting power at multiple operating frequencies and autonomously adapting itself to the dominant ambient frequencies. It consists of a compact dual-frequency resonator designed such that the first two fundamental natural frequencies are in the range of [50, 100] Hz, which is a typical frequency range for ambient vibrations in industrial environments. A magnetic frequency-tuning scheme is incorporated into the structure, which enables the frequency agility of the system. In contrast to single frequency harvesters, the presented approach combines multi-resonance and frequency tunability of both modes enabling a larger operative bandwidth. We experimentally demonstrate independent bi-directional tunability of our dual-frequency design. Furthermore, a control algorithm based on maximum amplitude tracking has been implemented for self-adaption of the system. The latter has been demonstrated in a system-level simulation model, which integrates the dual-frequency resonator, the magnetic tuning, and the control algorithm.

In response to the dilemma between economic development and environmental protection, green finance is an effective tool for environmental regulation. Based on the stochastic frontier analysis method to measure the energy efficiency of China’s provinces from 2001 to 2017, the promotion effect of green finance on energy efficiency and the intermediary effect of green technology innovation are tested and analyzed in our study. The results show that green finance can significantly improve energy efficiency. Specifically, green finance makes stronger effect on energy efficiency in provinces with rich resource endowments, high levels of economic development, and high degree of marketization. Green finance can improve energy efficiency through the development of new energy technologies and disruptive green innovation, which provides important supports for formulating policies to optimize energy structure and improve energy efficiency.