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N6-methyladenosine (m6A) is a representative of RNA methylation modification, which plays a critical role in the epigenetic modification process of regulating human diseases. As a key protein for m6A, methyltransferase 3 (METTL3) had been identified to be associated with a variety of diseases. The publications related to METTL3 were searched in the Web of Science Core Collection from the earliest mention to July 1st, 2022. Being screened by the retrieval strategy, a total of 1,738 articles related to METTL3 were retrieved. Much of our work focused on collecting the data of annual publication outputs, high-yielding countries/regions/authors, keywords, citations, and journals frequently published for qualitative and quantitative analysis. We found that diseases with high correlations to METTL3 not only included various known cancers but also obesity and atherosclerosis. In addition to m6A-related enzyme molecules, the most frequent key molecules were MYC proto-oncogene (C-MYC), Enhancer of zeste homolog 2 (EZH2), and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN). METTL3 and methyltransferase 14 (METTL14) may function through opposite regulatory pathways in the same disease. “Leukemia,” “Liver Cancer,” and “Glioblastoma” were speculated to be potential hotspots in METTL3 related study. The number of publications had significantly surged year by year, demonstrating the growing importance of the research on epigenetic modification in the pathology of various diseases.

Understanding the near-ground vertical and temporal photochemical O3 formation mechanism is important to mitigate the O3 pollution. Here, we measured the vertical profiles of O3 and its precursors at six different heights from 5-335 m using a newly built vertical observation system in Pearl River Delta (PRD) region, China. The net photochemical ozone production rate (P (O3)net) and O3 formation sensitivities at various heights were diagnosed using an observation-based model coupled with the Master Chemical Mechanism (MCM v3.3.1). Moreover, for the assessment of model performance and the causative factors behind O3 pollution episodes, the net photochemical ozone production rate (P (O3)net) was measured at 5 m ground level utilizing a custom-built detection system. In total three O3 pollution episodes and two non-episodes were captured. The identified O3 pollution episodes were found to be jointly influenced by both photochemical production and physical transport, with local photochemical reactions play a dominate role. The high index of agreement (IOA) calculated from comparing the modelled and measured P (O3)net values indicated the rationality to investigate the vertical and temporal variability of O3 formation mechanism using modelling results. However, the measured P (O3)net values were generally higher than the modelled P (O3)net values, particularly under high NOx conditions, which may indicate a potential underestimation of total RO2 by the model. Throughout the measurement period, the contribution of different reaction pathways to O3 production remained consistent across various heights, with HO2+NO as the major O3 production pathway, followed by RO2+NO. We saw P (O3)net decreased with the increase of the measurement height, primarily attributed to the decreased O3 precursors anthropogenic organic compounds (AVOC) and oxygenated volatile organic compounds (OVOC). O3 formation regimes were similar at different heights during both episodes and non-episodes, which was located either in volatile organic compounds (VOCs) sensitive regime or in transition regime and more sensitive to VOCs. Diurnally, photochemical O3 formation typically remained in the VOCs sensitive regime during the morning and noon time, but in the transitional regime and more sensitive to VOCs in the afternoon at around 16:00 LT. The vertical and temporal O3 formation are most sensitive to AVOC and OVOC, which suggests that targeting VOCs, especially AVOC and OVOC, for control measures is more practical and feasible at the observation site. The vertical temporal analysis of O3 formation mechanisms near the ground surface in this study provides critical foundational knowledge for formulating effective short-term emergency and long-term strategies to combat O3 pollution in the PRD region of China. [ABSTRACT FROM AUTHOR]

Purpose: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. Materials and Methods: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/ FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. Results: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells' (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. Conclusions: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective: Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase‐like 3 (METTL3) in affecting PCa development by regulating miR‐148a‐3p expression via N6‐methyladenosine (m6A) modification was investigated. Methods: METTL3, miR‐148a‐3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT‐qPCR and Western blotting. The m6A modification level of miR‐148a‐3p was observed by Me‐RIP assay. Bioinformatics website predicted miR‐148a‐3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual‐luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK‐8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry. Results: METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up‐regulated miR‐148a‐3p by promoting the m6A modification of pri‐miR‐148a‐3p in PCa cells. miR‐148a‐3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR‐148a‐3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down‐regulating miR‐148a‐3p and up‐regulating TXNIP. Conclusion: METTL3 promoted miR‐148a‐3p by mediating the m6A modification of pri‐miR‐148a‐3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice. [ABSTRACT FROM AUTHOR]

Abstract Oesophageal cancer (OC) is associated with high morbidity and mortality, and surgery is the most effective approach to treat it. In order to reduce surgical risks and duration of surgery, we explored a new strategy to determine tumour margins in surgery. In this study, we included 128 cancerous and 128 noncancerous database entries obtained from 32 human patients. Using internal extractive electrospray ionization-MS, in positive ion detection mode, the relative abundances of m/z 104.13, m/z 116.10, m/z 132.13, and m/z 175.13 were higher in cancer tissue while the relative abundances of m/z 82.99, m/z 133.11, m/z 147.08, m/z 154.06, and m/z 188.05 were higher in normal tissue. Using partial least squares analysis, the mass spectra of cancer samples was discriminated from those of normal tissues, and the discriminatory ions were obtained from loading plots. Dimethylglycine(m/z 104), proline(m/z 116), isoleucine(m/z 132), asparagine(m/z 133), glutamine(m/z 147), and arginine(m/z 175) were identified by collision-induced dissociation experiments. Using the ROC curve analysis, we verified the validity of six amino acids for the identification of tumour tissue. Further investigations of tissue amino acids may allow us to better understand the underlying mechanisms involved in OC and develop novel means to identify tumour tissue during operation.