Xinzhou Zhang

Background: Osteoporosis is a major public health concern worldwide. As the predominant and long-lived bone cells, osteocytes serve as key regulators of bone remodeling and mechanotransduction. However, the molecular mechanisms underlying their regulatory roles remain poorly understood. The roles of talin1, a key focal adhesion protein linking integrins to the cytoskeleton, in regulation of osteocyte function and skeletal homeostasis remain unclear.

Background: Epithelial-mesenchymal transition (EMT) of tubular epithelial cells are one of the major pathological changes of diabetic nephropathy (DN). Cluster of differentiation 248 (CD248) has been reported to be associated with fibrosis after kidney injury. The aim of this study was to investigate the mechanism of CD248 in DN and its targeted compounds. Materials and methods: Virtual screening, molecular docking and Cellular thermal shift assays were used to explore potential small molecule compounds targeting CD248. In vitro DN model was established by treating human proximal renal tubular epithelial cell line HK-2 with high glucose (HG), and db/db mice were used as the animal model. siRNA transfection was used to knockdown CD248 in HK-2 cells, and HK-2 cells and the animals were treated with veratramine (VER) or neobavaisoflavone (NBIF). qPCR was used to detect the mRNA expression of CD248, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 (IL-6), and IL-1β. Western blot was used to assess protein expression level of CD248, EMT-associated proteins, fibrosis markers, and TGF-β1/Smads pathway-associated proteins. CCK-8 assay and flow cytometry were used to detect cell viability and apoptosis, respectively. Histopathological and various biochemical indicators were used to assess renal injury in animals. Results: CD248 was significantly up-regulated in HG-induced HK-2 cells. CD248 knockdown inhibited HG-induced cell proliferation inhibition, apoptosis and inflammatory response. HG stimulation significantly reduced the protein expression level of E-cadherin in HK-2 cells, and increased the expression levels of vimentin, α-smooth muscle actin (α-SMA), collagen I, collagen IV, fibronectin, TGF-β1, p-Smad2, p-Smad3, and Smad4, while CD248 knockdown reversed these effects. In addition, VER and neobavaisoflavone were found to bind with CD248, and they inhibited HG-induced apoptosis, inflammation, EMT and extracellular matrix synthesis in HK-2 cells, and ameliorate the renal injury of db/db mice. VER and NBIF also inhibited HG-induced activation of TGF-β1/Smads axis. Conclusion: CD248 participates in HG-induced EMT of renal tubular epithelial cells and renal fibrosis by regulating TGF-β1/Smads pathway, and VER and NBIF are two potential natural drugs which targets it to ameliorate DN.

Background: Chronic kidney disease (CKD) is associated with various health complications, including sleep disorders. Understanding the relationship between CKD and sleep disturbances is essential for improving patient management and outcomes in this population. Patients and methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) across two cycles (2015–2016 and 2017-2018), involving 4758 participants aged 20 years and older. Sleep disorders were evaluated via targeted questions from the Sleep Disorders Questionnaire. Chronic kidney disease (CKD) was classified by low estimated glomerular filtration rate (eGFR) and proteinuria. Logistic regression analyses examined the association between sleep disorders and CKD, adjusting for demographic and lifestyle confounders. Results: Among 4,758 participants, 863 (14%) were diagnosed with chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels and differential leukocyte counts were observed in the CKD cohort. CKD was associated with increased reports of snoring, sleep apnea, and sleep disturbances, along with higher fatigue levels. A significant positive association between CKD and sleep difficulties persisted in adjusted models. Infrequent snoring (1–2 times per week) demonstrated a negative association, whereas excessive daytime sleepiness (16–30 times/month) correlated positively with CKD. Significant associations between sleep disorders and CKD were observed in participants aged <60, with a BMI <28 kg/m², normal blood pressure, and CRP ≥1.8 mg/L. Sleep disorders were found to be correlated with obesity, hypertension, diabetes, CKD, and proteinuria. Notably, CKD patients with sleep difficulties had markedly elevated CRP levels compared to those without sleep issues, while other inflammatory markers were similarly elevated (P < 0.001). Conclusion: Patients with chronic kidney disease experience higher rates of sleep issues, highlighting the importance of addressing these problems in CKD management.

Purpose: This study aimed to investigate the impact of mental health and lifestyle factors on women with angina with nonobstructive coronary arteries (ANOCA), and to identify potential risk factors associated with ANOCA. Methods: In this cross-sectional study, 84 female patients diagnosed with ANOCA and 42 age-matched healthy women served as controls. All participants underwent endothelial function testing and laboratory assessments. Demographic data, psychological status, and lifestyle behaviors were evaluated using self-administered questionnaires, Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), and Post-Traumatic Stress Disorder Checklist—Civilian Version (PCL-C). Group differences in key variables were analyzed, and logistic regression was performed to identify independent risk factors and examine potential mediation effects. Results: Compared with controls, women with ANOCA exhibited significantly higher scores on HADS-depression, HADS-anxiety, PCL-C, and PSS, along with lower exercise frequency, elevated serum hs-C-reactive protein (hs-CRP), and higher white blood cell (WBC) counts (all P < 0.05). They were also more likely to report anxiety, depression, post-traumatic stress symptoms, poor sleep quality, and short sleep duration (all P < 0.05). Hypertension was more prevalent in ANOCA group, while no difference was found in peripheral vascular function. After multivariable adjustment, depressive symptoms, higher PSS scores, elevated WBC counts, and hs-CRP levels were identified as independent risk factors. Mediation analysis revealed that anxiety fully mediated the associations of exercise frequency (β = − 0.07, P > 0.05) and poor sleep quality (β = 0.48, P > 0.05) with ANOCA, and partially mediated the link between short sleep duration and ANOCA (β = 1.86, P < 0.01). Conclusion: Women with ANOCA are more likely to experience psychological distress, unhealthy lifestyle habits, and systemic inflammation. Depression, perceived stress, elevated WBC counts, and hs-CRP levels are independent risk factors, and unhealthy lifestyle may affect ANOCA by exacerbating anxiety.

Introduction: Epilepsy is a neurological disorder characterized by sudden, abnormal discharges of neuronal activity in the brain. Electroencephalogram (EEG) analysis is the primary technique for detecting epileptic seizures, and accurate seizure detection is essential for clinical diagnosis, therapeutic intervention, and treatment planning. However, traditional methods rely heavily on manual feature extraction, and current deep learning-based approaches still face challenges in frequency adaptability, multi-scale feature integration, and phase alignment.Methods: To address these limitations, we propose an Adaptive Multi-Scale Phase-Aware Fusion Network (AMS-PAFN). The framework integrates three novel components: (1) a Dynamic Frequency Selection (DFS) module employing Gumbel-SoftMax for adaptive spectral filtering to enhance seizure-related frequency bands; (2) a Multi-Scale Feature Extraction (MCFE) module using hierarchical downsampling and temperature-controlled multi-head attention to capture both macro-rhythmic and micro-transient EEG patterns; and (3) a Multi-Scale Phase-Aware Fusion (MCPA) module that aligns temporal features across scales through phase-sensitive weighting.Results: The AMS-PAFN was evaluated on the CHB-MIT dataset and achieved state-of-the-art performance, with 98.97% accuracy, 99.53% sensitivity, and 95.21% specificity (Subset 1). Compared to STFTormer, it showed a 1.58% absolute improvement in accuracy (97.39% → 98.97%) and a 2.66% increase in specificity (92.55% → 95.21%). Ablation studies validated the effectiveness of each module, with DFS improving specificity by 6.87% and MCPA enhancing cross-scale synchronization by 5.54%.Discussion: The AMS-PAFN demonstrates strong potential for clinical seizure recognition through its adaptability to spectral variability and spatiotemporal dynamics, making it well-suited for integration into real-time epilepsy monitoring and alert systems.

Objective: The American Heart Association has recently emphasized the significance of the cardiovascular-kidney-metabolic (CKM) syndrome. However, the cumulative impact of these factors on cardiorespiratory fitness remains inadequately characterized. This study aimed to examine the responses observed during cardiopulmonary exercise testing (CPET) of CKM syndrome patients and explore the potential correlation between cardiorespiratory fitness and hemoglobin concentration in this cohort. Design: Cross-sectional study. Methods: We retrospectively collected medical data of 8206 patients who underwent CPET from 2012– 2022. Among the 878 individuals enrolled, 12 were healthy controls, 809 had isolated CVD, and 57 were in CKM stage 4. After propensity score matching, 112 patients were included in the matched cohort analysis, with 56 each in the CVD and CKM groups. CPET responses were compared between the groups using propensity matched analysis. Additionally, simple mediation models were employed to investigate the potential mediating role of hemoglobin concentration in the association between CKM syndrome and peak VO₂. Results: After propensity score-matching, CKM stage 4 was associated with diminished cardiorespiratory fitness compared to the other two groups. This included diminished exercise capacity, reflected by shorter exercise time, lower maximum workload (and its percent predicted value), and reduced peak VO2 (including its percent predicted value and peak VO2/kg). Additionally, cardiac autonomic function was impaired, as evidenced by decreased heart rate recovery (HRR) and a reduced slope of HR recovery (all p< 0.05). Mediation model regression analysis indicated a significant and direct detrimental effect of CKM syndrome on peak VO₂ (β = − 228.502; P = 0.003), and a significant indirect partial effect of hemoglobin concentration on the direct effect (β = − 335.718; P < 0.001), with the percentage mediated through hemoglobin concentration of 46.9%. Conclusion: Individuals with CKM syndrome demonstrate compromised responses to CPET manifested by diminished exercise capacity and cardiac autonomic function. While diminished peak oxygen uptake can be partly explained by hemoglobin concentration as we found, further research is necessary to understand other underlying mechanisms.