Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome.

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Comprehensive assessment of fine motor movement and cognitive function among older adults in China: a cross-sectional study.

BACKGROUND: Fine motor skills are closely related to cognitive function. However, there is currently no comprehensive assessment of fine motor movement and how it corresponds with cognitive function. To conduct a complete assessment of fine motor and clarify the relationship between various dimensions of fine motor and cognitive function. METHODS: We conducted a cross-sectional study with 267 community-based participants aged ≥ 60 years in Beijing, China. We assessed four tests performance and gathered detailed fine motor indicators using Micro-Electro-Mechanical System (MEMS) motion capture technology. The wearable MEMS device provided us with precise fine motion metrics, while Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. We adopted logistic regression to analyze the relationship between fine motor movement and cognitive function. RESULTS: 129 (48.3%) of the participants had cognitive impairment. The vast majority of fine motor movements have independent linear correlations with MoCA-BJ scores. According to logistic regression analysis, completion time in the Same-pattern tapping test (OR = 1.033, 95%CI = 1.003-1.063), Completion time of non-dominant hand in the Pieces flipping test (OR = 1.006, 95%CI = 1.000-1.011), and trajectory distance of dominant hand in the Pegboard test (OR = 1.044, 95%CI = 1.010-1.068), which represents dexterity, are related to cognitive impairment. Coordination, represented by lag time between hands in the Same-pattern tapping (OR = 1.663, 95%CI = 1.131-2.444), is correlated with cognitive impairment. Coverage in the Dual-hand drawing test as an important indicator of stability is negatively correlated with cognitive function (OR = 0.709, 95%CI = 0.6501-0.959). Based on the above 5-feature model showed consistently high accuracy and sensitivity at the MoCA-BJ score (ACU = 0.80-0.87). CONCLUSIONS: The results of a comprehensive fine-motor assessment that integrates dexterity, coordination, and stability are closely related to cognitive functioning. Fine motor movement has the potential to be a reliable predictor of cognitive impairment.

Interaction between smoking during pregnancy and gestational diabetes mellitus and the risk of cesarean delivery: evidence from the National Vital Statistics System 2019.

OBJECTIVE: To explore the interaction between smoking during pregnancy (SDP) and gestational diabetes mellitus (GDM) on the risk of cesarean delivery. METHODS: This retrospective cohort study utilized data from the National Vital Statistics System (NVSS) 2019. The NVSS database provides data on births and deaths as well as maternal characteristics in the United States. The duration of follow-up was 38.74 ± 2.12 weeks. The outcome was the method of delivery, including vaginal and cesarean delivery. The multivariate logistic regression model was adopted to assess the associations of SDP and GDM with the method of delivery. The interaction between SDP and GDM was examined via calculating the relative excess risk of interaction (RERI), the attributable proportion of interaction (API) and the synergy index (S). Subgroup analyses were conducted based on age, race, prepregnancy body mass index (BMI), and primiparity. RESULTS: The study included 3352615 puerperae. Compared with women who did not smoke during pregnancy, those who smoked during pregnancy had a significantly higher risk of cesarean delivery [odds ratio (OR)=1.07, 95% confidence intervals (CI): 1.05-1.10, p < 0.001]; women with GDM had a significantly greater risk of cesarean delivery than those without (OR = 1.31, 95%CI: 1.30-1.33, p < 0.001). In contrast to women who did not smoke during pregnancy and did not have GDM, those who smoked during pregnancy and had GDM exhibited an increased risk of a cesarean section (OR = 1.47, 95%CI: 1.40-1.54, p < 0.001). RERI was 0.08 (95%CI: 0.01-0.15), API was 0.06 (95%CI: 0.01-0.10), and S was 1.21 (95%CI: 1.04-1.40) suggested that there was an interaction between SDP and GDM, and it was a synergistic effect. There was a synergism between SDP and GDM in women of non-advanced age (RERI = 0.07, 95%CI: 0.001-0.15; API = 0.05, 95%CI: 0.003-0.10; S = 1.17, 95%CI: 1.001-1.36), in white women (RERI = 0.08, 95%CI: 0.004-0.16; API = 0.05, 95%CI: 0.01-0.10; S = 1.19, 95%CI: 1.02-1.39), in women who were overweight before pregnancy (RERI = 0.13, 95%CI: 0.05-0.21; API = 0.08, 95%CI: 0.04-0.13; S = 1.33, 95%CI: 1.14-1.55), and in primiparae (RERI = 0.20, 95%CI: 0.08-0.31; API = 0.12, 95%CI: 0.06-0.19; S = 1.50, 95%CI: 1.23-1.84). CONCLUSION: SDP and GDM were associated with an increased risk of cesarean delivery, and a synergistic effect existed between SDP and GDM on the risk of cesarean delivery, especially in women of non-advanced age, white women, women who were overweight before pregnancy, and primiparae.

LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes.

Diabetic nephropathy (DN), characterized by glomerular injury, is a common complication of both type 1 and type 2 diabetes, accompanied by massive proteinuria. Podocytes are reported to play pivotal roles in maintaining the glomerular filtration barrier. In addition, the expression of long non-coding RNAs (lncRNAs) ANRIL was upregulated in type 2 diabetes patients. Hence, the aim of this study was to investigate the underlying mechanisms implicated the role of LncRNA ANRIL in podocyte injury in DN. The concentration of inflammatory cytokines was quantified by the corresponding enzyme-linked immunosorbent assay (ELISA) kits. The mRNA levels of the target gene were determined by reverse transcription and real-time quantitative PCR (RT-qPCR). The expressions of proteins were evaluated by Western blot. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) level were measured by corresponding commercial kits. Finally, the apoptosis of podocytes was analyzed by TUNEL assay. In our study, LncRNA ANRIL was highly expressed in high glucose (HG)-induced podocytes. Moreover, LncRNA ANRIL silencing attenuated HG-induced inflammation, oxidative stress, and apoptosis and induced MME overexpression in podocytes. Interestingly, MME knockdown abolished the suppressive effect of LncRNA ANRIL silencing on HG-induced inflammation, oxidative stress, and apoptosis in podocytes. LncRNA ANRIL silencing alleviates HG-induced inflammation, oxidative stress, and apoptosis via upregulation of MME in podocytes. Hence, LncRNA ANRIL may be a novel and effective target to ameliorate podocyte injury in DN.