Search Results (522)

Background/Objectives: Ganglion cells are the projection neurons of the retina, and there are multiple types that differ in their morphology, light responses and central projections. Parasol cells are one of the major retinal ganglion cell types in primates. The presynaptic bipolar cells have been well-characterized, but less is known about the amacrine cells that provide the majority of their inputs. The goal of this study was to identify the amacrine cells presynaptic to the OFF subtype of parasol cells. Methods: Central retinal tissue from an adult macaque was processed for serial block-face scanning EM, and a volume of images of the inner retina located 2 mm temporal to the center of the fovea was analyzed. Results: All the OFF parasol cells in the volume were reconstructed. All the synaptic inputs of two OFF parasol cells were analyzed. They received 80% or more of their input from amacrine cells and the remainder from bipolar cells, almost entirely from the Off diffuse type. Many of the presynaptic amacrine cells were reconstructed sufficiently to be classified as wide-field or narrow-field, and the latter type predominated. Five specific types of presynaptic amacrine cells were identified as AII, A4, knotty bistratified type 1, A13 and wiry type 1. Notably, the same types of amacrine cells are also presynaptic to OFF midget ganglion cells, another major type. Conclusions: These findings suggest that differences between the light responses of midget and parasol ganglion cells likely arise from differences in the presynaptic bipolar cell types. Full article

In view of the fact that there are few reports on the preparation of NbC coating by high-power pulsed magnetron sputtering (HiPIMS) technology. In this study, the effects of NbC interlayer thickness on the microstructure, corrosion resistance and electrical conductivity of Nb/NbC/C multilayer coatings for proton exchange membrane fuel cell (PEMFC) bipolar plates were studied by using the high ionization characteristics of HiPIMS technology. A series of Nb/NbC/C multilayer coatings with varying NbC interlayer thicknesses was deposited via HiPIMS by modulating the deposition time (20, 40, and 60 min). The microstructure and properties of the coatings were characterized using scanning electron microscopy (SEM), Raman spectroscopy, interfacial contact resistance (ICR), and corrosion current, among other methods. The results indicate that as the NbC interlayer thickness increases, the total coating thickness increases from 0.43 μm to 1.42 μm. All coatings exhibit a uniform and dense microstructure lacking typical coarse columnar structures. Raman and XPS analyses show that the I_D/I_G ratio increases from 1.98 to 4.04, indicating an increase in sp²-hybridized bond content and a decrease in sp³ content. At a deposition time of 60 min, the coating achieved optimal performance, yielding a critical load (Lc1) of 31.9 N, the lowest average friction coefficient (0.27), the minimum corrosion current density, and an interfacial contact resistance of 7.5 mΩ·cm². These results demonstrate that the NbC interlayer thickness significantly governs the structure and properties of the Nb/NbC/C multilayer coatings. Specifically, an appropriate increase in the NbC interlayer thickness optimizes the sp²/sp³ hybrid bond ratio, thereby enhancing the overall coating performance. Full article

Psychiatric disorders represent a leading cause of disability worldwide and are characterized by substantial biological and therapeutic heterogeneity. Despite significant research efforts, peripheral biomarkers capable of guiding diagnosis, patient stratification, and personalized treatment selection are still lacking. Circulating cell-free DNA (cfDNA) has recently emerged as a promising candidate biomarker, as it may integrate signals of cellular damage, apoptotic activity, and immune activation across multiple tissues. Beyond its role as a marker, cfDNA may also actively contribute to disease processes by functioning as a damage-associated molecular pattern (DAMP), thereby perpetuating inflammatory signaling. The mitochondrial component of cfDNA (cf-mtDNA), which also possesses strong immunostimulatory properties, represents a particularly sensitive indicator of mitochondrial vulnerability to stress. In this context, the present review aims to synthesize the most recent evidence on cfDNA and cf-mtDNA in major psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). Specifically, we examine their association with psychological stress exposure and childhood trauma, as well as their involvement in inflammation-related pathophysiological mechanisms such as mitochondrial dysfunction, oxidative stress, and hypothalamic–pituitary–adrenal (HPA) axis dysregulation. Available evidence suggests that alterations in cfDNA may be present in subgroups of patients with MDD, BD, and SCZ. However, findings remain heterogeneous and sometimes contradictory, partly due to methodological limitations, including the lack of standardized analytical protocols and insufficient control for potential confounders. Nevertheless, cfDNA holds promise as a tool for inflammation-based patient stratification and for informing personalized therapeutic strategies. Future research directions include the integration of cfDNA within multi-omics frameworks, the analysis of cfDNA methylation profiles to infer tissue of origin, and the exploration of pharmacological strategies aimed at modulating cfDNA as a potential therapeutic target. Full article

Optogenetic gene therapy-based treatment offers a unique approach to bypass dysfunctional or degenerated photoreceptors in retinal degenerative disorders. Ambient light-activatable multi-characteristic opsin (MCO) targeted to bipolar cells of the retina has demonstrated partial vision restoration in animal models of retinitis pigmentosa (RP). Here, we describe the potential therapeutic efficacy of intravitreally delivered AAV-carried MCO-010 in a mouse model of Stargardt disease. MCO-010 treatment led to significantly improved behavioral outcomes in the visually guided radial arm water maze. Furthermore, longitudinal optical coherence tomographic imaging showed that the MCO-010 treatment led to no notable change in the retina thickness. Furthermore, the MCO-010-treated mice exhibited higher electrophysiological responses compared to the control group. Together, these findings demonstrate potential vision-restoring and disease-modifying aspects of ambient light-activatable intravitreal MCO-010 therapy. Full article

Bipolar plates are critical components of proton exchange membrane fuel cells (PEMFCs), strongly influencing thermal management, mechanical stability, and overall system efficiency. In this study, an integrated framework combining multiphysics simulation, artificial intelligence (AI), and data augmentation techniques was developed for PEMFC bipolar plate optimization. A coupled thermal–structural finite element model was established in COMSOL Multiphysics to evaluate temperature distribution, thermal stress, and structural deformation under varying operating conditions. A total of 80 parametric design cases were generated by varying six key parameters: hole radius, plate thickness, heating power, manifold pressure, plate number, and heat transfer coefficient. The dataset was expanded using SMOTE, GAN, and LLM-based augmentation techniques and used to train ANN, LR, RF, XGBoost, and SVR models. Model performance was evaluated using 5-fold cross-validation with MAE, RMSE, and LogCosh metrics. The results showed that ensemble tree-based methods, particularly RF and XGBoost, achieved the highest prediction accuracy and computational efficiency. XGBoost produced the best temperature prediction performance for the SMOTE-based dataset (RMSE = 3.668), while RF achieved the lowest stress prediction error (RMSE = 0.0490). GAN-augmented datasets provided stable and reliable predictions, whereas LLM-generated datasets resulted in higher prediction errors and lower physical consistency. Feature importance analysis revealed that plate thickness dominates displacement prediction (≈0.72 importance), manifold pressure governs stress behavior (≈0.999), and heating power is the primary factor affecting temperature prediction. The proposed AI-assisted surrogate modeling framework enables rapid and accurate thermo-mechanical prediction while significantly reducing computational cost compared to conventional multiphysics simulations. The findings demonstrate that integrating physics-based simulations with data-driven approaches provides an efficient strategy for the optimization of next-generation PEM fuel cell bipolar plates. Full article

Bipolar cancellation (BPC) is an efficiency-limiting phenomenon in bipolar nanosecond pulsed electric field (nsPEF) exposures, in which the second, opposite-polarity phase reduces or partially reverses the electroporation induced by the first phase. Nisin, a cationic antibiotic peptide, has been reported to interact with lipid membranes in bacterial systems and artificial bilayer models, where it may contribute to membrane destabilization and increased permeability during pulsed electric field exposure. This study investigated whether nisin may enhance the efficacy of bleomycin electrochemotherapy (ECT) in the presence of bipolar nanosecond pulses, which are typically associated with pronounced BPC effects. Pulsed electric field (PEF) parameters and drug concentrations were selected based on preliminary viability and Yo-Pro-1 uptake experiments in CLS-354 human squamous cell carcinoma cells. To evaluate the effect of nisin, cell viability and membrane permeabilization were assessed following exposure to 300 ns pulses across a range of bipolar PEF protocols, with or without nisin, while identical unipolar pulses were used for comparison. Nisin (50 µg/mL) increased membrane permeabilization across the tested range of field amplitudes (9–15 kV/cm) and burst repetition frequencies (0.1–1.66 MHz). The presence of nisin was also associated with increased efficacy of bleomycin-based ECT under both unipolar and symmetrical bipolar PEF conditions. Under the optimized parameters tested (13 kV/cm; 150 pulses of 300 ns at 1.66 MHz), bipolar nsPEFs in combination with nisin reached levels of efficacy comparable to those observed with unipolar waveforms, suggesting a potential attenuation of bipolar cancellation effects. Full article

Severe mental disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), are leading causes of global disability, yet current treatments remain largely symptomatic and fail to alter disease trajectories. Converging evidence from genetics, longitudinal studies, and systems neuroscience supports a dimensional and transdiagnostic architecture of psychopathology, involving shared polygenic risk and overlapping neurodevelopmental and circuit-level alterations. Traditional approaches—such as post-mortem brain analysis, neuroimaging, and animal models—have delineated core molecular perturbations (e.g., dopaminergic, glutamatergic, and GABAergic dysfunction), as well as informed translational frameworks for mechanistic investigation, but remain constrained by restricted access to dynamic processes and incomplete recapitulation of human-specific biology. The advent of human-derived cellular models, particularly human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), has partially addressed these limitations, enabling the study of patient-specific neurodevelopment and synaptic function in vitro. Within this evolving landscape, the olfactory neuroepithelium (ONE) has emerged as an accessible source of neural progenitors, obtainable through minimally invasive procedures, providing a window into living human neurobiology. ONE-derived cells retain donor-specific genetic and epigenetic signatures while recapitulating disease-relevant phenotypes across major psychiatric disorders, including altered neurodevelopmental dynamics, synaptic gene expression, and inflammatory profiles. Here, we present a narrative review of the principal cellular and tissue models used in biological psychiatry, examining their respective strengths, limitations, and translational relevance across experimental contexts. By situating these approaches within a unified framework, we aim to clarify their complementarity, identify current gaps, and outline future directions, highlighting the emerging potential of ONE-based models to bridge genetic risk, cellular dysfunction, and clinical phenotype, thereby advancing precision psychiatry. Full article

Major depressive disorder (MDD) is associated with altered membrane lipids, but the causal species remain uncertain. Using two-sample Mendelian randomization (MR) on lipidomic GWAS data and the latest MDD meta-analysis (~400,000 cases; 1.5 million controls), we identified 49 lipid species linked to MDD risk, notably enriched for phosphatidylcholines. Protective lipids were enriched for long-chain polyunsaturated fatty acids (20:3–20:5), whereas shorter-chain or less unsaturated species, particularly 18:2-containing lipids, increased risk. These associations were also observed in a subset of clinically assessed MDD cases. Colocalization supported shared causal variants between many lipid traits and MDD, prominently at the FADS1/2 locus and additional loci, suggesting multiple entry points into lipid metabolism that differ partly from bipolar disorder. MR-implicated lipid shifts overlapped with cortisol-induced changes in a human cell stress model and were often reversed by co-treatment with St. John’s wort extract (Ze 117). Cholesteryl ester 20:3 emerged as a robust candidate marker, showing protective MR effects in two cohorts, colocalizing genetic support, normalization by Ze 117, and an inverse correlation with depressive symptom severity in a non-clinical sample. Together, these results define a depression-associated lipidomic signature centered on polyunsaturated fatty acid metabolism with biomarker and therapeutic potential. Full article

Decarbonizing air travel poses a major technological challenge, driven by the substantial power requirements of the drivetrain and the demanding weight and volume constraints of airborne systems. One promising avenue involves leveraging the high specific energy of hydrogen by designing compact, high-power fuel cell stacks to supply power for electric drivetrains. However, a key drawback of such propulsion architectures is the substantial heat generated within the fuel cells, which necessitates bulky and heavy thermal management systems to ensure safe and continuous operation. This study investigates a proposed air-based thermal management system, which operates by introducing pulsating heat pipes into the bipolar plates of a High-Temperature Polymer Electrolyte Membrane Fuel Cell (HT-PEM FC) stack. If proven to be feasible, heat pipe assisted air cooling may provide the benefit of reducing overall system complexity by decreasing the number of components in the thermal management system. To evaluate the thermal performance of the proposed system, a one-dimensional thermal model was initially developed in a previous study to describe the temperature distribution along the length of a heat pipe. Building upon this foundation, the present work extends the model by incorporating a two-dimensional Computational Fluid Dynamic (CFD) analysis to account for geometry-specific effects within the hexagonal design. Results indicate that the heat transfer from the hexagonal heat pipe geometry to the coolant air flow was marginally overestimated in previous analytical calculations. Revised heat transfer rates led to a shift in the predicted temperature distributions, resulting in the need for either increased external airflow, extended condenser sections, or reduced inlet temperatures to maintain target operating conditions. Although these adjustments may result in a slight increase in system mass and parasitic power consumption, the overall impact is limited, and the heat pipe-assisted air cooling approach remains theoretically feasible. Based on the results, design modifications are proposed and their impact on thermal performance is evaluated to address the challenges of heat rejection and temperature uniformity. A modification based on variation and optimization of PHP meander lengths was evaluated using the updated model and it significantly improved temperature homogeneity across the evaporator. Full article

Bipolar disorder (BD) is characterized by mood swings between mania and depression, sharing overlapping symptomatic and genetic risk factors with other mood disorders. Long non-coding RNAs (lncRNAs) show specific spatiotemporal precision in distinct cell types in the human brain, and understanding the precise mechanisms of lncRNAs in mood switching in BD is fundamental to deciphering the key molecular networks underlying BD diagnosis and therapy. In this review, we summarize the classification of BD subtypes, the differences between BD and multiple mood disorders, and the functional potential of lncRNAs in BD. Future studies of these lncRNAs will facilitate the development of RNA-based diagnosis for BD. Full article

Background/Objectives: Total knee arthroplasty (TKA) is often associated with extensive bleeding and the need for intraoperative and postoperative blood transfusions. Due to concern about the risks associated with them, a push has been made in surgery toward the development of new intraoperative blood management devices and innovative postoperative care strategies. Tranexamic acid (TXA), fibrin sealant and standard electrocautery are widely used in orthopedic surgery, since several studies provided evidence about their efficacy and safety. A new device, the bipolar sealer system (BSS), provides hemostasis at lower temperature (<100°) than conventional electrocautery. It does not produce smoke, necrosis or burn tissue. Methods: In this study, we retrospectively analyzed data from 480 patients who underwent TKA between January 2017 and December 2024. The cohort was divided into two groups based on the hemostatic protocol adopted. The control group enrolled 240 patients who received the standard protocol with TXA and fibrin sealant, while the study group enrolled 240 patients who followed protocol with Aquamantys BSS and TXA. Hematological parameters, including hemoglobin (Hb), hematocrit (HCT) and red blood cells (RBCs) were analyzed preoperatively (T0) and postoperatively: immediately after surgery (T1), at day one (T2) and day three (T3). Results: Changes in hemoglobin from baseline to postoperative follow-up were significantly lower among patients who received TXA plus BSS and those receiving TXA plus fibrin sealant, with p-values of 0.0003 at T1 (immediately after surgery), 0.027 at T2 (one day post-op), and 0.0001 at T3 (three days post-op). Comparable results were observed for HCT and RBC values. Conclusions: These data demonstrate that Aquamantys is more effective than fibrin glue in controlling blood loss after knee replacement surgery, not only immediately after the procedure but also in the following days. Full article

This study investigated the comparative performance of anion exchange membranes (AEMs), cation exchange membranes (CEMs), and bipolar membranes (BPMs) in dual-chamber microbial fuel cells (MFCs) operated under fed-batch real wastewater conditions. The experimental studies focused on electrical output; pH shifts; and changes in chemical oxygen demand (COD), total nitrogen, total phosphorus, and ammonia concentrations. The results revealed distinct performance profiles for each membrane type. The CEM system supported high removal of COD, TN, and ammonia (≈75–85% ± 2%). In contrast, the AEM achieved excellent phosphorus removal (≈95% ± 2%) alongside strong COD reduction, although nitrogen and ammonia removal were comparatively lower. BPM systems exhibited lower COD removal (typically <65%) but achieved moderate and stable reductions in TN, ammonia, and phosphorus while producing electrical output consistently higher than AEMs and at intermediate levels relative to CEMs. Quantitative analysis of power generation further confirmed this trend, with CEM delivering the highest output (8.93 mW/m²), BPM providing moderate performance (3.38 mW/m²), and AEM producing the lowest (1.5 mW/m²). The results emphasize that membranes influence the balance between nutrient removal and energy recovery and that aligning membrane selection with specific treatment objectives may advance MFCs from laboratory demonstrations toward practical applications. Full article

This narrative review outlines the structure and essential functions of ocular proteoglycans (PGs) in visual processing as documented in the extensive literature on this subject matter. The eye, as one of the most complex sensory organs, relies on the coordinated activity of various tissues and cell types, with PGs playing a central role in facilitating communication and maintaining tissue function. These molecules stabilise ocular tissues; for example, SPACRCAN (IMPG2) and hyaluronan aggregates in the interphotoreceptor matrix protect photoreceptors from oxidative stress. Specialised heparan sulfate PGs, such as pikachurin, eyes-shut, and the neurexin family, stabilise synapses and ensure synaptic specificity and plasticity. Pikachurin is particularly important for the rapid transmission of visual signals at the bipolar ribbon synapse. A diverse array of chondroitin sulfate (aggrecan, versican, neurocan, brevican, phosphacan, NG2), keratan sulfate (SV2), and heparan sulfate (perlecan, agrin, collagen XVIII) PGs are differentially expressed in ocular tissues, contributing to tissue stability and homeostasis. In the cornea, sclera, and choroid, small leucine-rich repeat PGs (SLRPs) maintain three-dimensional structure, corneal transparency, and tissue function through interactions with cytokines and growth factors. The vitreous humour contains opticin and nyctalopin, which support the nutrition of avascular regions and facilitate bipolar ribbon synapse signalling. Ultimately, the effectiveness of the eye as a visual organ depends significantly on the functional roles of its constituent PGs. Full article

The miniature (mini) Ossabaw pigs are proposed as a translational preclinical model for testing and developing novel therapeutics for human diseases, including cystic fibrosis, cancer, and metabolic syndrome (MetS). In recent years, pigs have gained similar attention for studying retinal abnormalities and disorders owing to their close resemblance in size, anatomy, vasculature, and pathology to the human eye compared with their rodent counterparts. In our previous study, Ossabaw minipigs fed a Western diet for 10 weeks and followed for 3.5 months exhibited early signs of retinal degeneration and vascular abnormalities, mimicking the early stages of diabetic retinopathy (DR). To further evaluate pathomorphological alterations across neuronal and non-neuronal cell types, the present study comprehensively investigated individual retinal layers using cell-type-specific immunostaining. We found that the Western diet-fed mini pigs had reduced rhodopsin and blue opsins, changes in bipolar and ganglion cells, and reduced density of pre- and post-synaptic connections. Moreover, the retinas of obese mini pigs showed evidence of gliosis and microglial activation. Our findings suggest that a Western diet-induced metabolic disorder exhibits an early neurodegenerative milieu and further demonstrate the suitability of Ossabaw mini pigs as a model for human retinal diseases associated with MetS, such as DR and diabetic macular edema (DME). Full article

Background: Oxidative stress (OS) has been widely implicated in pathophysiology of major psychiatric disorder. However, establishing robust causal links and delineating the specific molecular mechanisms involved continue to pose significant research challenges. Methods: We performed a multi-omics analysis focusing on 817 oxidative stress-related genes (OSGs) in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). We applied summary data-based Mendelian randomization (SMR), integrating large-scale genome-wide association studies for MDD, BD, and SCZ with quantitative trait loci datasets from both blood and brain tissues, including measures of DNA methylation, gene expression, and protein abundance. Results: Multi-omics integration yielded supportive evidence across blood and brain tissues implicating ACE and ACADVL in SCZ, where genetically predicted increases in their methylation, expression, and protein abundance were associated with reduced disease risk. IGF1R was associated with bipolar disorder (BD) risk in blood-specific analyses. Brain-specific analyses further nominated ENDOG as a candidate gene for SCZ. Single-cell SMR indicated that increased ENDOG expression was associated with higher SCZ risk in astrocytes, CD4⁺ naïve T cells, CD8⁺ effector T cells, and natural killer cells, suggesting a potential immune–brain interaction. Conclusions: This study provides multi-level genetic evidence supportive of a potential causal role for specific OSGs in major psychiatric disorders. We identify ACE, ACADVL, IGF1R, and ENDOG as candidate genes for further investigation, offering insights into epigenetic and transcriptional mechanisms that could inform future research on therapeutic targets. Full article