Carcinoembryonic antigen (CEA) is a key tumor biomarker, and its sensitive detection is critical for early diagnosis and treatment monitoring. This work presents a novel “turn-on” fluorescent aptasensor for sensitive and cost-effective detection of CEA, based on a FAM-labeled CEA aptamer (FAM-Aptamer) as the recognition unit, and Ce-UiO-66 nanoparticles as an efficient quenching platform. The Ce-UiO-66 material was synthesized and comprehensively characterized by SEM, TEM, XPS, FT-IR, Raman and XRD, demonstrating a high quenching efficiency (QE) of 99.95
Bisphenol A (BPA), an environmental endocrine disruptor, is implicated in hepatocellular carcinoma (HCC), but its molecular mechanisms are unclear. This study employed an integrative computational framework to identify potential BPA-related molecular targets in HCC, assess their statistical clinical value, and generate hypotheses regarding their roles within the tumor microenvironment. BPA and HCC targets were retrieved from public databases and intersected with differentially expressed genes in HCC, identifying fifteen overlapping genes statistically enriched in cell cycle regulation, p53 signaling, and viral carcinogenesis. Six hub genes (MKI67, CCNA2, EZH2, CCNB1, CDK1, BIRC5) were significantly upregulated in HCC with high internal cross-validated diagnostic accuracy (AUC > 0.96), although these estimates may be susceptible to overfitting and require external validation. Molecular docking and dynamics simulations predicted stable BPA binding to six proteins (Ki67, Cyclin A2, EZH2, Cyclin B1, CDK1, Survivin), with van der Waals forces calculated as the primary driving energy contribution by MM-PBSA. The two-gene (CCNB1/EZH2) risk model showed statistical associations with patient survival, validated internally and externally, although its generalizability remains limited. Mendelian randomization provided genetic evidence consistent with a potential risk-associated role for CCNB1 and a protective-associated role for EZH2. Single-cell analysis localized high CCNB1 and EZH2 expression to malignant and proliferative T-cells, correlating with specific immune infiltration patterns and checkpoint expression. In conclusion, these computational findings suggest a statistical and structural association between BPA exposure and HCC-related core cell-cycle regulators (e.g., CCNB1/EZH2). The data generate the hypothesis that CCNB1 and EZH2 may serve as prognostic biomarkers and potential contributors to HCC biology, possibly through coordinated effects on cell cycle dysregulation and immune microenvironment remodeling, though direct evidence of in vivo molecular targeting by BPA or causal pathway activation is not established by this study. These findings provide novel insights into BPA’s putative role in hepatocarcinogenesis and offer clues for future experimental validation regarding risk assessment and therapeutic strategies.
Bone mass accumulation in childhood and adolescence forms the foundation for lifelong bone health, and vitamin D deficiency remains prevalent. This study aims to investigate the association between dietary patterns in children and adolescents and bone health. This study population comprised 3,299 children and adolescents aged 6 to 18 from Shenzhen, China. Dietary intake data were collected using a validated semi-quantitative food frequency questionnaire (FFQ). Bone health was assessed by measuring the speed of sound (SOS) in the calcaneus using quantitative ultrasound (QUS). The SOS reflects bone density and microstructure, with a higher value indicating better bone quality. Dietary patterns were extracted from 18 food groups using principal component analysis (PCA) and reduced-rank regression (RRR). The 25-hydroxyvitamin D (25(OH)D) level was chosen as the response variable for RRR, quantified by liquid chromatography-mass spectrometry. The association between dietary patterns and SOS by means of generalized linear models (GLM) and restricted cubic splines models (RCS). Five dietary patterns were identified via PCA, namely the ultra-processed, seafood-egg-soup, plant-based, meat-based, and nut-dairy-fruit dietary patterns. RRR identified a vitamin D-related dietary pattern characterized by high consumption of fish and other seafood, dairy, fruits, and eggs, and low consumption of snack foods and fried foods. Both the nut-dairy-fruit (β = 3.50, 95
Abstract Objective To investigate the utility of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) for early detection of renal injury 24 h after cardiac arrest and cardiopulmonary resuscitation. Materials and methods Twenty-four male Sprague–Dawley rats were randomized into cardiac arrest (n = 15) and sham-operated (n = 9) groups. Five cardiac arrest rats died during the procedure, resulting in 10 cardiac arrest and 9 sham rats for analysis. IVIM-MRI and renal parameters were assessed 24 h after cardiac arrest and cardiopulmonary resuscitation. Diffusion-related parameters, including apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and exponential ADC (eADC), were obtained. The primary imaging endpoint was defined as D. Following completion of MRI, renal function, histopathology, and expression of apoptosis markers (Bcl-2, Caspase-3), water channel protein aquaporin-3, and tight junction proteins (zonula occludens-1, occludin) were subsequently evaluated. Results Despite preserved conventional renal function, IVIM MRI detected early renal alterations 24 h after cardiac arrest. Compared with the sham group, eADC, D, ADC, D*, and f values were all significantly reduced. Histopathological analysis revealed pronounced tubular epithelial injury, increased apoptosis (Bcl-2, p < 0.001; Caspase-3, p = 0.010), and reduced expression of aquaporin-3 (p = 0.039), zonula occludens-1 (p < 0.001), and occludin (p < 0.001). Conclusion IVIM MRI enables early, noninvasive detection of renal injury 24 h after cardiac arrest and CPR, reflecting tubular injury, tight junction disruption, and perfusion deficits, potentially facilitating timely intervention and improving prognosis. Relevance statement This approach may facilitate individualized therapy and improve post-cardiac arrest syndrome outcome. Key Points The long-term outcomes of cardiac arrest remain poor due to post-cardiac arrest syndrome. IVIM MRI enables early, noninvasive detection of renal injury after cardiac arrest and cardiopulmonary resuscitation. This approach may facilitate individualized therapy and improve post-cardiac arrest syndrome. Graphical Abstract
The pathogenesis of primary aldosteronism (PA) remains incompletely understood. Current pharmacological therapies have significant limitations, thus highlighting the importance of recognizing new therapeutic targets for the diagnosis and treatment of PA. This study employed two-sample Mendelian randomization (MR) analysis, colocalization, summary data-based Mendelian randomization (SMR) analysis, and mediation analysis to recognize new therapeutic targets for the diagnosis and treatment of PA. Our analysis revealed a significant positive connection between increased FES eQTL expression and reduced PA risk. Concurrently, to elucidate the underlying metabolic mechanisms through which the FES eQTL influences PA, we identified immune cells as significant mediators of this pathway. Specifically, The FES eQTL was found to elevate the risk level of CD3 expression on TD CD8br immune cells (OR = 1.116885, 95
