As one of the prevalent posttranscriptional modifications of RNA, N⁷-methylguanosine (m⁷G) plays essential roles in RNA processing, metabolism, and function, mainly regulated by the methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) complex. Emerging evidence suggests that the METTL1/WDR4 complex promoted or inhibited the processes of many tumors, including head and neck, lung, liver, colon, bladder cancer, and teratoma, dependent on close m⁷G methylation modification of tRNA or microRNA (miRNA). Therefore, METTL1 and m⁷G modification can be used as biomarkers or potential intervention targets, providing new possibilities for early diagnosis and treatment of tumors. This review will mainly focus on the mechanisms of METTL1/WDR4 via m⁷G in tumorigenesis and the corresponding detection methods.

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world’s population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD expresses normal or low body mass index; thus, the condition is called non-obese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. Furthermore, preclinical results from non-obese animal models with NAFLD are unclear. Gut microbiota and their metabolites in non-obese/lean-NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora, and intestinal metabolites in a non-obese NAFLD mouse model established using a methionine-choline-deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels, as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16S RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes:Bacteroidota ratio was increased. g_ Tuzzerella , s_ Bifidobacterium pseudolongum , and s_ Faecalibaculum rodentium were the predominant species in non-obese NAFLD mice. Fecal metabolomics using liquid chromatography-tandem mass spectrometry revealed the potential biomarkers for the prognosis and diagnosis of non-obese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid, and estriol. Our findings could be useful to identify and develop drugs to treat non-obese NAFLD and lean NAFLD. IMPORTANCE: Patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4′-phosphate, together with the predominant flora including g_ Tuzzerella , s_ Bifidobacterium pseudolongum , and s_ Faecalibaculum rodentium , were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant.

Objective: This study explores the cost-effectiveness of atezolizumab monotherapy compared with chemotherapy as first-line treatment for stage IIIB or IV non-small cell lung cancer (IIIB/IV-NSCLC) ineligible for platinum-based chemotherapy from a US payer perspective.Design: This is based on the IPSOS clinical trial. We conducted a comprehensive assessment of the cost-effectiveness of atezolizumab monotherapy versus single-agent chemotherapy over a 15-year duration. Employing a robust Markov model incorporating data from 453 patients, we calculated total costs, life-years (LYs), quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of $150 000 per QALY. We performed one-way, two-way and probabilistic sensitivity analyses to validate our model.Setting: The US payer perspective.Participants: A cohort with NSCLC ineligible for treatment with a platinum-containing regimen from IPSOS clinical trial.Interventions: Atezolizumab monotherapy versus chemotherapy.Primary outcome measure: Cost, QALYs, LYs and ICER.Result: Chemotherapy resulted in an average survival of 0.930 QALYs (1.528 LYs) per patient at an average cost of $67 579. Atezolizumab treatment provided an additional 0.309 QALYs but incurred an extra cost of $66 472, leading to an ICER of $215 069 per QALY compared with chemotherapy. The cost of atezolizumab had the most significant impact on the model outcomes. Probabilistic sensitivity analysis showed that atezolizumab had a 30.2% probability of being considered cost-effective at a WTP threshold of $150 000 per QALY in the USA. These results remained consistent across various scenarios and sensitivity analyses employing both deterministic and probabilistic approaches.Conclusion: The current price of atezolizumab renders it an unlikely cost-effective treatment option for patients with IIIB/IV-NSCLC from the payer’s perspective in the USA. To achieve cost-effectiveness, substantial discounts are necessary.Trial registration number: The IMpower-110, an open-label, randomised, phase 3 clinical trial (NCT02409342). The IPSOS clinical trial (NCT03191786).