Aberrant METTL14 gene expression contributes to malignant transformation of benzene-exposed myeloid cells.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Unlocking synergies of drawdown operation: Multi-objective optimization of reservoir emergency storage capacity.

Optimizing reservoir drawdown operations holds significant implications for hydropower generation, water supply, and drought mitigation strategies. However, achieving multi-objective optimization in reservoir drawdown operations poses fundamental challenges, particularly considering emergency storage capacity and seasonal drought patterns. This study introduces a novel multi-objective optimization framework tailored for a mega reservoir, focusing on drawdown operations to enhance hydropower generation and water supply reliability. A drawdown operation model leveraging a multi-objective ant lion optimizer is developed to simultaneously maximize reservoir hydropower output and minimize water shortage rates. China's Three Gorges Reservoir (TGR), situated over the upper reaches of the Yangtze River, constitutes the case study, with the standard operation policy (SOP) serving as a benchmark. Results showcase the efficacy of the proposed method, with substantial improvements observed: a 10.6% increase in hydropower output, a 6.0% reduction in water shortage days, and a 9.5% decrease in minimal reservoir water release compared to SOP. This study provides robust technical and scientific bolster to optimize reservoir ESC and enhance the synergy between hydropower generation, water supply, and drought resilience. Additionally, it offers decision-makers actionable strategies that account for emergency water supply capacities. These strategies aim to support mega reservoir's resilience against extreme drought events facilitating the collaboration between modelers and policy-makers, by means of intelligent optimization and decision-making technologies.

A rapid near-infrared turn on fluorescence probe for the detection of sulfite in food and its application in biological imaging.

A near-infrared fluorescent "turn on" probe DTMI featuring simple skeleton was constructed easily. It undergoes a structure transformation from an A-π-A to a D-π-A framework towards SO32-. Besides, DTMI is capable of distinctive sensing sulfite with a fast response and a significant Stokes shift as well as with high sensitivity, excellent selectivity, long-term stability of fluorescence signals, and good anti-interference ability. The detection limit (LOD) of DTMI for sulfite within the linear concentration range of 0.5-10 µM is 27.39 nM. More importantly, DTMI has been favorably utilized for detecting sulfite in food samples such as red wine and vermicelli. Based on its low biotoxicity, DTMI has been successfully applied in imaging experiments involving HeLa cells, onion inner epidermal cells, and zebrafish. Therefore, the results show that the presented probe possesses potential sensing activity towards sulfite in complex biological system and food samples.