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Functional studies of the RNA N 6 -methyladenosine (m 6 A) modification have been limited by an inability to map individual m 6 A-modified sites in whole transcriptomes. To enable such studies, here, we introduce m 6 A-selective allyl chemical labeling and sequencing (m 6 A-SAC-seq), a method for quantitative, whole-transcriptome mapping of m 6 A at single-nucleotide resolution. The method requires only ~30 ng of poly(A) or rRNA-depleted RNA. We mapped m 6 A modification stoichiometries in RNA from cell lines and during in vitro monocytopoiesis from human hematopoietic stem and progenitor cells (HSPCs). We identified numerous cell-state-specific m 6 A sites whose methylation status was highly dynamic during cell differentiation. We observed changes of m 6 A stoichiometry as well as expression levels of transcripts encoding or regulated by key transcriptional factors (TFs) critical for HSPC differentiation. m 6 A-SAC-seq is a quantitative method to dissect the dynamics and functional roles of m 6 A sites in diverse biological processes using limited input RNA. m 6 A-SAC-seq uses chemical labeling to quantify m 6 A at single-base resolution in the mammalian transcriptome.

Multiple myeloma (MM) and its precursors monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are 2–3 times more common in African Americans (AA) than European Americans (EA). Although epigenetic changes are well recognized in the context of myeloma cell biology, the contribution of 5-hydroxymethylcytosines (5hmC) to racial disparities in MM is unknown. Using the 5hmC-Seal and next-generation sequencing, we profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 342 newly diagnosed patients with MM ( n  = 294), SMM ( n  = 18), and MGUS ( n  = 30). We compared differential 5hmC modifications between MM and its precursors among 227 EA and 115 AA patients. The captured 5hmC modifications in cfDNA were found to be enriched in B-cell and T-cell-derived histone modifications marking enhancers. Of the top 500 gene bodies with differential 5hmC levels between MM and SMM/MGUS, the majority (94.8%) were distinct between EA and AA and enriched with population-specific pathways, including amino acid metabolism in AA and mainly cancer-related signaling pathways in EA. These findings improved our understanding of the epigenetic contribution to racial disparities in MM and suggest epigenetic pathways that could be exploited as novel preventive strategies in high-risk populations.

N -methyldeoxyadenosine (6mA or m dA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited. We use Tetrahymena thermophila as a model organism to examine the effects of 6mA on nucleosome positioning. Independent methods reveal the enrichment of 6mA near and after transcription start sites with a periodic pattern and anti-correlation relationship with the positions of nucleosomes. The distribution pattern can be recapitulated by in vitro nucleosome assembly on native Tetrahymena genomic DNA but not on DNA without 6mA. Model DNA containing artificially installed 6mA resists nucleosome assembling compared to unmodified DNA in vitro. Computational simulation indicates that 6mA increases dsDNA rigidity, which disfavors nucleosome wrapping. Knockout of a potential 6mA methyltransferase leads to a transcriptome-wide change of gene expression. These findings uncover a mechanism by which DNA 6mA assists to shape the nucleosome positioning and potentially affects gene expression.

Background N 6 -methyldeoxyadenosine (6mA or m 6 dA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited. Results We use Tetrahymena thermophila as a model organism to examine the effects of 6mA on nucleosome positioning. Independent methods reveal the enrichment of 6mA near and after transcription start sites with a periodic pattern and anti-correlation relationship with the positions of nucleosomes. The distribution pattern can be recapitulated by in vitro nucleosome assembly on native Tetrahymena genomic DNA but not on DNA without 6mA. Model DNA containing artificially installed 6mA resists nucleosome assembling compared to unmodified DNA in vitro. Computational simulation indicates that 6mA increases dsDNA rigidity, which disfavors nucleosome wrapping. Knockout of a potential 6mA methyltransferase leads to a transcriptome-wide change of gene expression. Conclusions These findings uncover a mechanism by which DNA 6mA assists to shape the nucleosome positioning and potentially affects gene expression.

Functional studies of the RNA N -methyladenosine (m A) modification have been limited by an inability to map individual m A-modified sites in whole transcriptomes. To enable such studies, here, we introduce m A-selective allyl chemical labeling and sequencing (m A-SAC-seq), a method for quantitative, whole-transcriptome mapping of m A at single-nucleotide resolution. The method requires only ~30 ng of poly(A) or rRNA-depleted RNA. We mapped m A modification stoichiometries in RNA from cell lines and during in vitro monocytopoiesis from human hematopoietic stem and progenitor cells (HSPCs). We identified numerous cell-state-specific m A sites whose methylation status was highly dynamic during cell differentiation. We observed changes of m A stoichiometry as well as expression levels of transcripts encoding or regulated by key transcriptional factors (TFs) critical for HSPC differentiation. m A-SAC-seq is a quantitative method to dissect the dynamics and functional roles of m A sites in diverse biological processes using limited input RNA.

IntroductionFirst-degree relatives of colorectal cancer (CRC) patients have a twofold to fourfold increased risk of CRC. Tailored communication interventions have shown efficacy in improving their risk awareness and screening participation. While computer-based tailoring systems offer convenience, they often overlook the integration of healthcare professionals’ verbal input, potentially limiting effectiveness and long-term impact. To address this gap, we developed ScreenTalk, an intelligent voice-interactive tailored communication system that employs intelligent speech interaction to automate the tailoring process, enhance message credibility and improve scalability within CRC screening workflows.Methods and analysisThis study is a two-arm, cluster-randomised controlled trial with a hybrid type I design involving 314 participants across three tertiary general hospitals in Guangzhou, China. Participants in both groups will receive usual care. Additionally, the intervention group will receive a 1-month tailored intelligent voice-interactive intervention, whereas the control group will receive unrelated health education to control for attention. Screening uptake (primary outcomes) and health beliefs (secondary outcomes) are measured at baseline and at 3 months, 6 months, 9 months and 12 month post the intervention. Implementation outcomes including reach, implementation, adoption and maintenance will be assessed through questionnaire, qualitative interviews and tailored system record.Ethics and disseminationThe trial has been approved by the Ethics Committee of the Sun Yat-sen University (IRB No. L2024SYSU-HL-054). Information on the purpose and process of this study will be provided to the participants before recruitment, and written signatures will be collected from all participants to ensure their voluntary participation and protection of their rights and privacy.Trial registrationNCT06710860 on ClinicalTrials.gov. Registered 26 November 2024. Date and version: 3.0, 14 July 2025.

The essential cause of menopause is ovarian failure, which can cause decline in sex hormones (especially estrogen) that can increase the risk of metabolic diseases, such as cardiovascular disease and osteoporosis. This study screened 1511 eligible patients from 2148 perimenopausal and postmenopausal women, measuring various physiological and biochemical indicators to analyze differences among age groups (40–44, 45–49, and 50–54 years) with laboratory techniques. The study found no significant difference in the incidence of cardiovascular disease betweenperimenopausal and postmenopausal women. But the incidence of osteoporosis was higher in postmenopausal women and was associated with age ( p  < 0.05). Additionally, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), total cholesterol (TC), lumbar spine bone mineral density (BMD) (T1), right femoral BMD (T2) and femoral neck BMD were significantly correlated in both groups. Significant differences were observed in FSH, LH, E 2 , TC, low-density lipoprotein (LDL), L2-L4, T 1 , femoral neck reduction and T 2 among women in different age groups. Correlation analysis indicated that age increased the risk of cardiovascular disease and osteoporosis in bothperimenopausal and postmenopausal women. This study contributes to a deeper understanding of the pathogenesis of cardiovascular disease and osteoporosis in perimenopausal and menopausal women.