Tang Hospital

Autophagy has recently attracted increasing attention for its critical involvement in Alzheimer’s Disease (AD) pathogenesis. However, the role of microtubule-associated protein 1 light chain 3 A (LC3A) and B (LC3B), key autophagic-associated proteins in cognitive decline, AD risk, and underlying pathology remain unclear. This study included 568 participants from the Alzheimer’s Disease Neuroimaging Initiative with cerebrospinal fluid (CSF) measurements of LC3A and LC3B. We systematically assessed the associations of LC3A and LC3B with cognition, dementia risk, AD biomarkers, microglial activity, brain volume, and metabolism through both cross-sectional and longitudinal analyses. Additionally, subgroup analyses based on ATN classification were conducted to evaluate stage-specific effects, and Receiver operating characteristic (ROC) analyses were employed to explore the clinical predictive value of LC3A and LC3B. Finally, mediation models were used to investigate the potential mechanisms by which LC3A and LC3B affect AD pathology and cognition. Elevated CSF LC3A and LC3B levels were negatively associated with cognition, while positively associated with amyloid deposition, total tau (t-tau), phosphorylated tau (p-tau), progranulin (PGRN), and soluble Triggering Receptor Expressed on Myeloid Cells-2 (sTREM2) at baseline. Higher CSF LC3A and LC3B concentrations were linked to an increased risk of dementia, accelerated longitudinal cognitive decline, greater brain atrophy, faster accumulation of t-tau, and longitudinal associations with sTREM2. Individuals with TN+ exhibited significantly higher CSF LC3A and LC3B levels compared to those with TN−. Moreover, CSF LC3A alone could predict TN−/TN+ status with an area under the curve (AUC) of 0.903, which increased to 0.939 when combined with amyloid PET. Similarly, CSF LC3B alone yielded an AUC of 0.876, rising to 0.913 when combined with amyloid PET. Finally, amyloid deposition and microglial activation individually or jointly, mediated the effects of LC3A and LC3B on tau pathology and cognitive decline. CSF LC3A and LC3B, reflecting autophagic activation, are linked to elevated tau pathology and an increased risk of AD. They may jointly contribute to AD pathological progression alongside amyloid deposition and microglial activation. LC3A and LC3B as robust candidate biomarkers for monitoring pathological burden, stratifying disease risk, and informing clinical evaluation in AD.

BackgroundMedulloblastoma (MB) is a common central nervous system malignancy in children, and its relationship with lactate metabolism has become an important area of cancer research in recent years, especially in metabolic reprogramming. This study aimed to determine the effects of lactate metabolism-related genes in the biological mechanisms involved in MB.MethodsA single-cell analysis was performed on the GEO dataset (GSE155446) in order to analyse the lactate metabolism-related characteristics of differing MB cell populations. Following this, MB cells were divided according to their lactate metabolism-related characteristics, and further developmental trajectories between MB subsets were analyzed. Further studies encompassed cell communication and pathway analysis to elucidate their function and association with immune cells. Additionally, a MB-related bulk dataset (GSE85217) was procured for machine learning-based identification of core lactate-metabolism related genes, with the objective of gaining novel insights into clinical diagnosis and therapeutic targets.ResultsIn light of the findings from the scRNA-seq analysis, three primary cell types were identified. It was found that cells in MB clusters exhibited distinct biological functions. Metabolic analysis of MB clusters revealed heterogeneity in glycolysis, gluconeogenesis, and lactate metabolism reprogramming. The lactate-metabolism related genes score (LMRGs score) was found to be significantly elevated in MB clusters. Furthermore, differential expression analysis among MB cell clusters revealed distinct metabolic profiles. The Random Forest learning method confirmed that COX4I1, CYC1, MECP2, MYC, NDUFAF3, NDUFS3, COX20, CALR, POMT1 and C1QBP are highly expressed in MB.ConclusionsThe results of the present study demonstrate a close association between lactate-metabolism-related genes and their functions, and the development of MB.

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES 1999-2004), including 19,507 participants. Multivariable weighted logistic were employed to investigate the association of serum albumin with hypertension. The potential mediating role of body mass index (BMI), C-reactive protein (CRP), and extracellular fluid (ECF) was explored. Secondary analyses included subgroup analyses and restricted cubic spline (RCS). Serum albumin per 1 g/L increase was associated with 10% lower hypertension prevalence (OR=0.90, 95%CI:0.89-0.91, p <0.001). This remained significant after full adjustment (including age, sex, race/ethnicity, education level, smoking status, drinking status, sodium in-take, potassium intake, fat intake, total saturated fatty acids [TSFA] intake, carbohydrate intake, protein in-take, energy intake, diabetes, coronary heart disease, creatinine, alanine aminotransferase [ALT], and NHANES cycle)(OR = 0.98, 95%CI: 0.96-1.00, p = 0.031). No evidence of non-linearity was observed in the RCS analysis (p for non-linearity = 0.708). BMI mediated 42.75% (95%CI: 38.19%-48.33%), CRP 12.24% (95%CI: 9.29%-15.43%), and ECF 4.05% (95%CI: 2.74%-5.43%) of the association (all p <0.001). Results were robust in sensitivity analyses. The serum albumin levels were negatively associated with the prevalence of hypertension. Mediation analyses demonstrated a significant mediating effect of BMI, CRP and ECF, suggesting that serum albumin might be related to hypertension, potentially mediated by BMI, ECF, and CRP.

Acute coronary syndrome (ACS) is a high-risk disease among cardiovascular diseases. This study is to screen for lncRNA ceRNA regulatory network in acute coronary syndrome associated with percutaneous coronary intervention (PCI) and to validate the XIST/miR-212-3p/CALCOCO2/OPTN axes. lncRNA, miRNA, and mRNA expression microarray data were retrieved and downloaded from the GEO database. Dysregulated lncRNAs and miRNAs were collected using the GEO database. Target genes were predicted and subjected to KEGG pathway analysis. The serum levels of lncRNA XIST, miR-212-3p, CALCOCO2, and OPTN were detected by RT-qPCR. The H9C2 hypoxia-reoxygenation (H/R) injury model was established. The cell viability was detected. The related indicators of mitophagy were detected by flow cytometry and Western blot. Six PCI-related lncRNAs were identified in ACS, linked to 44 PCI-associated miRNAs and 159 PCI-associated mRNAs. KEGG pathway analysis suggested the mitophagy pathway, which involved XIST/miR-212-3p/CALCOCO2/OPTN axes. The levels of XIST, CALCOCO2, and OPTN were increased while the level of miR-212-3p was decreased in PCI patients. Taken together, our results suggest that lncRNA-miRNA-mRNA networks associated with PCI in ACS were presented. In the H/R cell model, XIST promoted mitophagy through miR-212-3p/CALCOCO2/OPTN. XIST can promote mitophagy through the miR-212-3p/CALCOCO2/OPTN axis, thereby alleviating myocardial cell injury.

Cardiometabolic multimorbidity (CMM) poses a significant global health challenge. The atherogenic index of plasma (AIP) is a promising biomarker for cardiometabolic risk, but there is limited information on its cumulative effect on CMM and the underlying mechanisms. This study investigated the association of cumulative AIP exposure with CMM risk, and explored the mediating roles of the triglyceride glucose (TyG) index and body mass index (BMI). This study was based on data from 5,454 participants from the China Health and Retirement Longitudinal Study (CHARLS, 2011 baseline). The participants were stratified into tertiles of cumulative AIP (cuAIP) and classified into three distinct AIP trajectory groups using k-means clustering. Associations between cuAIP levels, AIP trajectories, and CMM incidence were assessed using logistic. The relationship between cuAIP and CMM was further examined using receiver operating characteristic (ROC) curve analysis and restricted cubic splines (RCS). Structural equation modeling was used to evaluate the mediating roles of the TyG index and BMI. Finally, subgroup and sensitivity analyses were conducted to validate the results. A total of 385 CMM cases were observed during the 7-year follow-up. Cluster analysis revealed the highest CMM incidence (12.1%) in the persistently high AIP trajectory group. Logistic regression models indicated that the highest cuAIP group (OR 2.81, 95% CI: 1.95-4.14) and high AIP trajectory group (OR 2.34, 95% CI: 1.68-3.28) had the highest CMM risk, with consistent results in sensitivity analyses and most subgroups. The AUC of cuAIP for predicting CMM was 0.648, and RCS curves demonstrated increasing CMM incidence with rising cuAIP levels. Mediation analysis indicated that the TyG index and BMI mediated 74% and 26% of the total effect, respectively. This study establishes AIP as an independent predictor of CMM, whereby its effect is primarily mediated by the TyG index and BMI. These findings support the implementation of integrated clinical strategies to effectively prevent CMM and its associated diseases.

Assessing lesion severity and optimizing percutaneous coronary intervention (PCI) are crucial for improving long-term outcomes in patients with coronary artery disease. Both strategies offer advantages over angiography alone; however, direct comparisons for revascularization decision-making are limited. This study evaluates and compares outcomes of FFR versus intravascular ultrasound (IVUS)-guided PCI strategies. We searched PubMed, Cochrane Central, and ScienceDirect from inception till April 2025. Data for various outcomes were extracted after computing the random-effect model and risk ratio (RR) with a 95% confidence interval (CI). The quality assessment of the included randomized controlled trials and observational studies was conducted using the Cochrane Risk of Bias 2 (ROB-2) and the Newcastle-Ottawa Scale, respectively. Publication bias was assessed visually through funnel plots and statistically through Egger's regression test. We included 5 studies comparing FFR and IVUS in 4714 patients undergoing PCI. The FFR and IVUS groups demonstrated comparable results across all endpoints including major adverse cardiovascular events (RR: 1.05; 95% CI: 0.84-1.30; P = 0.68), all-cause mortality (RR: 0.84; 95% CI: 0.50-1.39; P = 0.49), cardiac death (RR: 1.05; 95% CI: 0.59-1.87; P = 0.87), nonfatal myocardial infarction (RR: 1.31; 95% CI: 0.70-2.44; P = 0.40), and target vessel revascularization (RR: 1.20; 95% CI: 0.78-1.84; P = 0.40). The FFR (either hyperemic or angiography-driven) and IVUS groups showed comparable clinical outcomes in PCI for intermediate coronary lesions. However, FFR adds value with enhanced cost-efficiency and a physiology-driven approach that avoids unnecessary interventions. Selection should depend on patient factors, operator expertise, and institutional resources.