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This cross-sectional study investigated the association between glaucoma and B vitamin dietary intake. A total of 5025 enrolled individuals participated in self-reported glaucoma questionnaire and 3264 participated in International Society Geographical and Epidemiological Ophthalmology (ISGEO) criteria. In self-reported glaucoma, the risk of having self-reported glaucoma was lower in the third quartile of vitamin B1 intake (odds ratio [odds ratio [OR] 0.63, 95% confidence interval [CI] 0.40–0.97), and P trend (P trend = 0.004) for vitamin B12 was significant; in males, the third quartile of vitamin B1 intake (OR 0.44, 95% CI 0.24–0.83) and the fourth quartile of vitamin B2 intake (OR 0.39, 95% CI 0.17–0.89) were associated with a lower risk. In glaucoma based on ISGEO criteria, the increase of niacin intake (OR 0.94, 95% CI 0.89–0.99) was negatively associated with the odds of self-reported glaucoma. After sex-stratified analysis, the third quartile of vitamin B6 intake (OR 0.21, 95% CI 0.08–0.60) in males were associated with reduced odds of glaucoma. The restricted cubic spline analysis revealed a nonlinear association of vitamin B2 (p for nonlinearity = 0.04) and B9 (p for nonlinearity = 0.024) intake with glaucoma diagnosed by ISGEO criteria in females.

Retinal diseases represent a leading cause of visual impairment and blindness worldwide, with early and accurate diagnosis being crucial for preventing irreversible vision loss. Although deep learning techniques have achieved significant advances in fundus image analysis, existing methods predominantly focus on single tasks, treating vessel segmentation and disease diagnosis as independent problems without fully leveraging their intrinsic relationships. Furthermore, the lack of transparency in deep model predictions limits clinical adoption; while full interpretability remains an open challenge, post-hoc techniques such as Grad-CAM can provide partial transparency by highlighting influential image regions. This study presents V-MNet, a vessel-guided multi-task deep learning framework that simultaneously achieves retinal vessel segmentation and multi-disease classification, and provides visual transparency through Grad-CAM-based class activation mapping to support clinical decision-making. The framework comprises three core modules: a shared encoder extracts multi-scale feature representations; a segmentation decoder employs a U-Net-style architecture to generate vessel masks; and a classification decoder incorporates an innovative vessel-guided mechanism that explicitly transfers structural priors from the segmentation branch to the classification task, enabling the model to precisely localize pathological regions. Concurrently, an integrated Grad-CAM module generates post-hoc class activation maps for each disease category, highlighting spatially relevant lesion regions for clinician review. Comprehensive experiments were conducted on four public datasets-RFMiD, ODIR-5K, DRIVE, and EyePACS-light-v2. Experiments demonstrate that V-MNet achieves a Dice coefficient of 0.831 and AUC of 0.985 for vessel segmentation tasks, and an average AUC of 0.978 with F1-score of 0.935 for multi-disease classification tasks, significantly outperforming single-task baseline models and existing state-of-the-art methods. Ablation studies systematically quantify the performance contributions of multi-task learning and the vessel-guided mechanism, confirming the effectiveness of the framework's core innovations. V-MNet demonstrates broad application potential as a computer-aided diagnostic tool by jointly leveraging vascular structure and disease pathology for superior performance and visual transparency. The vessel-guided multi-task design effectively exploits the intrinsic relationship between vessel segmentation and disease classification, while the integrated Grad-CAM module addresses the lack of model transparency, facilitating clinical adoption and supporting clinical decision-making.

The impact of environmental toxins, particularly organophosphate pesticides (OPs), on the progression of diabetic retinopathy (DR) remains insufficiently understood. Recent studies have highlighted the potential role of environmental pollutants in exacerbating diabetic complications, but the underlying mechanisms are still unclear. This study aims to explore the effect of diethyldithiophosphate (DEDT), an OP, on DR progression through modulation of the AMPK/Nrf2/HO-1 signaling pathway. Human retinal microvascular endothelial cells (HRMECs) and retinal pigment epithelial cells (ARPE-19) were cultured under high-glucose conditions to simulate diabetic stress. Cells were exposed to various concentrations of DEDT, and their viability, oxidative stress, tight junction integrity, and inflammation were assessed. Western blot, quantitative PCR, and enzyme-linked immunosorbent assay (ELISA) techniques were employed to evaluate the expression of key proteins in the AMPK/Nrf2/HO-1 pathway and inflammatory cytokines. In vivo, diabetic rat models were treated with DEDT to assess retinal damage and oxidative stress. The effects of AMPK activation were also evaluated using AICAR, an AMPK activator, to further explore the mechanistic role of AMPK/Nrf2/HO-1 signaling. Our results demonstrated that DEDT exposure significantly reduces retinal cell viability and disrupts tight junction proteins (ZO-1, Occludin, Claudin-5) under high-glucose conditions. Mechanistically, DEDT inhibited the AMPK/Nrf2/HO-1 pathway, leading to increased oxidative stress, enhanced inflammation, and elevated levels of apoptotic markers (Bax and Bcl-2). In vivo, DEDT exposure exacerbated retinal damage and oxidative stress in diabetic rats. Activation of AMPK by AICAR reversed these effects, restoring Nrf2 and HO-1 expression, improving cell viability, and protecting the blood-retinal barrier. These findings indicated that DEDT promotes DR progression by disrupting the AMPK/Nrf2/HO-1 signaling pathway. This study provided experimental evidence that DEDT accelerates diabetic retinopathy progression via inhibition of the AMPK/Nrf2/HO-1 pathway, contributing to increased oxidative stress and retinal barrier dysfunction. Our results emphasized the potential health risks associated with pesticide exposure, particularly in diabetic populations, and highlight the importance of regulating environmental toxins to prevent exacerbation of diabetic complications.

The study of retinal hemodynamics is pivotal for understanding both physiological and pathological conditions affecting the eye. Microcirculation in the retina exhibits unique rheological properties and flow dynamics compared to larger vessels. This computational study investigates the possible impact of elevated blood lipids on retinal vascular flow characteristics, focusing on viscosity increases and potential blockage effects. We utilized computational fluid dynamics to solve the incompressible Navier-Stokes equations for an image-based retinal vessel network under healthy conditions. Our findings reveal that arterial vessels have a higher average mainstream flow velocity than venous vessels, however, the latter experience higher wall shear stress (WSS) in those fine branch vessels, which are far away from the optical disc. Notably, vessels with more branches in the venous network are subjected to greater WSS. Then, we simulated the effect of elevated blood lipids by increasing venous viscosity by about 10-20%, which led to a proportional rise in WSS. Furthermore, we explored the potential blockage that may caused by elevated blood lipids, leading to localized increases in velocity and WSS. This study provides insights into the hemodynamic alterations induced by hyperlipidemia, highlighting the importance of considering systemic health parameters in ocular disease research and treatment.

The molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence of HSCs in vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance. Through our analyses, we nominate cooperating transcriptional regulators and identify how MECOM prevents the CTCF-dependent genome reorganization that occurs as HSCs differentiate. We show that this transcriptional network is co-opted in high-risk leukemias, thereby enabling these cancers to acquire stem cell properties. Collectively, we illuminate a regulatory network necessary for HSC self-renewal through the study of a rare experiment of nature. Modeling a rare bone marrow failure disorder due to haploinsufficiency for the MECOM transcription factor identifies a human hematopoietic stem cell regulatory network, which is co-opted by high-risk leukemias.

Background Angiogenesis and increased vascular permeability caused by endothelial cell dysfunction are crucial in diabetic retinopathy (DR). Pescadillo ribosomal biogenesis factor 1 (PES1) plays key roles in diabetes; however, its effect on DR has not been thoroughly investigated. This study evaluated the role of PES1 in angiogenesis and blood-retinal barrier functions of DR and explored the related regulatory mechanisms. Methods Integrated bulk RNA-seq and single-cell RNA-seq analyses were used to identify the key molecular target PES1 in this study. Western blot, scratch assay, tube formation assay, transwell, EdU proliferation assay, immunofluorescence, Evans Blue assay, PAS staining and H&E staining were used to detect the role of PES1 in angiogenesis and retinal barrier injury in vivo and in vitro, respectively. ChIP-seq was used to explore the regulatory mechanism. Results Integrated bulk RNA-seq and single-cell RNA-seq analyses revealed that high PES1 expression was significantly associated with DR. Under hyperglycemia conditions, elevated PES1 expression disrupted the retinal vascular barrier function and exacerbated vascular leakage and DR progression by inhibiting the expression of VE-cadherin and Occludin. Moreover, PES1 aggravated the imbalance between oxidation and anti-oxidation, leading to an excessive release of reactive oxygen species and further impairment of endothelial cell function. These biological processes were reversed by PES1-targeted siRNA/shRNA. Mechanistically, PES1 bound to the enhancer of VEGFR2 to regulate VEGFR2 mRNA expression, thereby influencing tube formation capacity and permeability of endothelial cells. Under diabetic conditions, PES1 upregulation was regulated by ELF3 binding to its promoter. Conclusions Our study confirmed that the ELF3/PES1/VEGFR2 signaling pathway is crucial for regulating retinal angiogenesis and blood-retinal barrier function in DR. Interventions targeting ELF3 or PES1 may serve as potential therapeutic strategies for DR.

To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16–13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.

Fabric composites are widely employed in self-lubricating bearing liners as solid lubrication materials. Although the tribological behaviors of fabric composites have been extensively studied, the cryogenic tribological properties and mechanisms have been scarcely reported and are largely unclear to instruct material design for aerospace and other high-tech applications. Herein, the tribological properties of polytetrafluoroethylene (PTFE)-based hybrid-fabric composites were investigated at cryogenic and ambient temperatures in the form of pin-on-disk friction under heavy loads. The results suggest that the friction coefficients of the hybrid-fabric composites obviously increase with a decrease in wear when the temperature drops from 25 to −150 °C. Moreover, thermoplastic polyetherimide (PEI), as an adhesive for fabric composites, has better cryogenic lubrication performance than thermosetting phenol formaldehyde (PF) resin, which can be attributed to the flexible chemical structure of PEI. The excellent lubrication performance of hybrid-fabric composites is attributed to the transfer film formed by PTFE fibers on the surface of fabrics.

To verify that Triptolide alleviates hyperosmotic stress-induced damage to human corneal epithelial cells (HCECs) by suppressing pyroptosis via the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor family, pyrin domain-containing 3 (TLR4/NF-κB/NLRP3) axis. HCECs were divided into six groups: control (CG), hyperosmotic model (MG, 500 mOsm for 12 h), hyperosmotic model with LPS (MG + LPS), triptolide intervention (THSG, 30 nM in 500 mOsm medium), triptolide with LPS (THSG + LPS), and triptolide-only (TOG, 30 nM in standard medium). Cell viability was detected using Cell Counting Kit-8 (CCK-8). The pyroptosis rate was measured by flow cytometry, and lactate dehydrogenase (LDH) release was quantified to assess cytotoxicity. Inflammatory cytokines interleukin-1β (IL-1β) and interleukin-8 (IL-8) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression levels of NLRP3 and NF-κB were analyzed by quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. NF-κB p65 nuclear translocation was detected by immunofluorescence. Compared to the CG (100.00 ± 0.00)%, MG significantly reduced HCECs proliferation to (54.47 ± 3.10)% and increased the pyroptosis rate to (40.28 ± 3.74)%. LPS further exacerbated these effects in the MG + LPS. The levels of inflammatory cytokines IL-1β and IL-8 were markedly elevated under hyperosmotic conditions, and further increased with LPS stimulation. THSG significantly ameliorated hyperosmotic-induced injury: cell proliferation increased to (86.47 ± 5.51)%, the pyroptosis rate decreased to (17.01 ± 2.33)%, and the release of IL-1β and IL-8 was substantially reduced. Triptolide also downregulated mRNA and protein expression of NLRP3 and NF-κB, and inhibited NF-κB p65 nuclear translocation. In the THSG + LPS group, triptolide partially reversed the LPS-enhanced inflammatory and pyroptotic responses, though its protective effect was attenuated compared to THSG without LPS. Notably, TOG showed no adverse effects on normal HCECs, with proliferation, pyroptosis rate, and inflammatory cytokine levels comparable to those of the CG. Triptolide alleviates hyperosmotic stress-induced pyroptosis and inflammatory injury in HCECs, likely through inhibiting the TLR4/NF-κB/NLRP3 pathway. This study suggests the potential of triptolide in treating hyperosmolarity-related ocular surface diseases.

Sloping seabeds are widely found in offshore areas, especially around coral reefs, where complex topography significantly affects wave–current propagation characteristics and seabed dynamic responses. However, previous studies have mainly focused on flat seabed cases, while investigations of sloping seabed responses around piles under wave–current interaction is limited. In this study, a three-dimensional numerical model is used to investigate the wave–current-induced sloping seabed response around a monopile. By comparing the variations in pore pressure and effective stress around the pile, the spatial heterogeneity of the seabed dynamic response was revealed. The results show that the variation in current velocity significantly affected the distribution of pore pressure and effective stress. Moreover, the disturbances on both lateral sides of the pile tended to stabilize as the current velocity increased, and the amplitude of the free surface gradually approached a steady state. This research fills the gap in the field of wave–current-induced sloping seabed response around piles and provides a theoretical basis for the analysis of offshore pile foundation stability under complex terrain conditions.