Search Results (20,103)

Astrocytes regulate key aspects of the neural microenvironment that can be co-opted by cancer to support tumor growth and invasion. Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is a matricellular glycoprotein expressed by astrocytes and stromal cells, whose expression varies across cancer types. While SPARCL1 is downregulated in many peripheral cancers, reports of its expression in gliomas, specifically glioblastoma (GBM), are inconsistent. The biological context underlying these divergent findings, and the role of SPARCL1 in GBM malignancy, remains unclear. Publicly available transcriptomic datasets from the Ivy Glioblastoma Atlas Project (Ivy GAP), GlioVis, and TCGA were analyzed to evaluate SPARCL1 expression across GBM cohorts. Spatially resolved gene expression data from Ivy GAP were used to assess SPARCL1 expression from defined tumor regions. Microarray and RNA sequencing datasets from GlioVis and TCGA, respectively, were used to assess SPARCL1 expression across whole-tumor samples. Spatial transcriptomics from Ivy GAP show SPARCL1 expression was upregulated along the leading edge and in infiltrating tumor regions. Microarray datasets showed greater SPARCL1 expression in tumors of astrocyte lineage as opposed to oligodendrocyte lineage. Bulk RNA sequencing showed high SPARCL1 expression in low-grade gliomas, which is consistent with astrocytic lineage, IDH mutation, and spatial averaging effects that might obscure regional associations. These findings demonstrate that SPARCL1 expression in GBM is shaped by tumor architecture, molecular classification, and microenvironment interactions. Enrichment of SPARCl1 at invasive tumor margins is consistent with prior studies linking SPARCL1 to neuron–glioma synapse formation and angiogenesis. Full article

Corner detection is a fundamental task in computer vision that plays a critical role in applications such as image registration, 3D reconstruction, and object tracking. In biological visual systems, simple cells in the primary visual cortex exhibit high selectivity to edge stimuli of specific orientations, while end-stopped cells can detect geometric singular structures such as line segment endpoints and corners. Existing corner detection methods based on visual neural computation typically employ a strategy of densely distributed end-stopped cells for corner localization, which suffers from significant localization deviation under small angle conditions due to mutual interference between responses of adjacent neurons. To address this problem, this paper proposes a bionic corner detection method based on cooperative processing of simple cells and end-stopped cells. The method constructs a two-stage cooperative processing framework: the edge filtering stage employs a Gabor filter bank to simulate the orientation selectivity of simple cells, extracting edge positions and orientation information; the dynamic construction stage builds unilateral end-stopped cells only at filtered edge positions based on local orientation information, fundamentally avoiding computational redundancy and response interference caused by global dense distribution; the corner localization stage determines precise corner coordinates through hierarchical clustering and dual-cluster centroid fusion strategies. Experimental results demonstrate that, in the 15° acute-angle regime where dense end-stopped schemes are most severely affected by response interference, the proposed method reduces the mean localization error from 8.76 to 2.34 pixels, corresponding to a 73.3% improvement; averaged across the eight tested angle levels from 15° to 165°, the improvement is approximately 40.9%, and all per-angle differences are statistically significant (paired t-test, p < 0.01 or below, N = 10 independent runs). On standard test images, the method attains the lowest mean localization error among the eight compared detectors (1.58 pixels, versus 1.68–3.42 pixels for Harris, FAST, COSFIRE, KAZE, SuperPoint, Deep Corner, and Wei et al.), while maintaining competitive detection rate, false-alarm rate, and runtime. Physiological plausibility validation experiments show that the correlation coefficient between the detection deviation of this method and human perceptual deviation reaches 0.923, indicating that the output of the framework aligns with previously reported human perceptual bias patterns and supporting its biological plausibility as a biologically inspired—rather than mechanistic—model of corner perception. The source code, dataset, and experimental results are publicly available (see Data Availability Statement). Full article

Once dismissed as “junk”, transposable elements (TEs) have recently gained recognition for their regulatory roles, notably in the brain and during development. The brain is hormone-responsive and the hippocampus in particular is sensitive to circulating gonadal hormones. While transcriptionally active, TE function remains poorly understood, especially in the brain. We and other researchers have shown that one particular TE RNA, B2 SINE ncRNA, is a regulator in the rodent hippocampus, especially after a psychologically stressful event like acute restraint stress. However, it is unknown if B2 SINE ncRNA is necessary for the proper development of hippocampal neurons, and, furthermore, if there are sex differences in this development. This work investigates the differences in the expression of B2 SINE RNA across sexes and its role in the development of primary hippocampal neurons. We utilized pooled locked nucleic acid (LNA) GapmeRs to knock down the expression of B2 SINE RNA, and we treated primary hippocampal neurons with dihydrotestosterone (DHT) to test if there is a difference in dendritic complexity. We used Sholl analysis to quantify branching, number of tips, and Sholl mean. We found a sex difference in both B2 SINE, higher in males compared to females, and ß-actin, lower in males compared to females. Additionally, knocking down B2 SINE RNA results in a reduction in dendritic complexity in male but not in female neurons. Taken together, this work suggests that B2 SINE RNA is expressed differentially and that it plays an important role in the proper development of hippocampal neurons in a sex-dependent manner. Our findings support the identification of a sex-specific biomarker that may enable individualized treatment of conditions influenced by sex. This is the first evidence of the role B2 SINE RNA may play in the regulation of the development of neuronal dendritic structure and the first to show differential regulation by sex. Full article

Introduction: This study explored how illness severity scores correspond to hypoxic-ischemic brain injury (HIBI) after cardiac arrest. Methods: This study included cardiac arrest survivors with sufficient data to calculate the Pittsburgh Cardiac Arrest Category (PCAC) and revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST) scores who underwent brain magnetic resonance imaging and cerebrospinal fluid neuron–specific enolase (CSF-NSE) measurement within 6 h after return of spontaneous circulation. The primary outcome was the association of PCAC and rCAST with quantitative brain injury markers assessed using whole brain mean apparent diffusion coefficient (mean ADC), low ADC volume fractions (PV600, 650, and 700), and CSF-NSE. Results: In total, 81 patients were included. PCAC was not significantly associated with CSF-NSE, mean ADC, or PVs. The rCAST score was significantly associated with higher CSF-NSE, lower mean ADC, and higher PV700. The neurologic sub-score of PCAC was independently associated with all evaluated brain injury markers, whereas the systemic sub-score was not. Of the individual rCAST components, anoxic time was independently associated with CSF-NSE, whereas no other single component was associated with these markers. Conclusions: rCAST was significantly associated with degree of HIBI, whereas PCAC was not. The neurologic sub-score of PCAC showed independent associations with HIBI. Full article

Tau is a protein associated with microtubules principally expressed in neuronal cells, where it plays a fundamental role in cytoskeleton stabilization and axonal transport. Several diseases collectively named tauopathies, such as Alzheimer’s disease, have been associated with an imbalance in the expression of alternative spliced Tau transcripts and the accumulation of hyperphosphorylated Tau, causing dysfunction and death of neuronal cells. Therefore, understanding the Tau exon splicing mechanisms may contribute to elucidating molecular factors that could underlie the development of neurodegenerative disorders. The aim of this study was to define the role of selected splicing factors in regulating Tau exon expression in cell lines and neuronal organoids. We demonstrated the role of the RNA-binding motif protein 20 (RBM20) splicing factor in regulating Tau exon 6 and exon 10, applying RNA-binding assay and qPCR analyses. Furthermore, we demonstrated that Tau expression was regulated during cerebral organoid differentiation, recapitulating in vivo Tau expression. These results suggest the feasibility of using brain organoid technology to study Tau alternative splicing during neural development, confirming that 3D cellular models could be used to study and characterize pathological processes taking place in Tau-related pathologies. Full article

Aiming at the problems of the large prediction error of model-driven algorithms and poor interpretability (even potential violation of physical laws) of pure data-driven algorithms in the prediction of aerospace vehicle plume characteristics, a physics mechanism-guided prediction algorithm for aerospace vehicle plume characteristics was proposed. Taking the long short-term memory (LSTM) network as the backbone, this algorithm constructed a hybrid physics–data model by embedding the prior knowledge of physical laws and empirical rules into the neural network, and designed a loss function combined with physical mechanisms to guide network training. The aerospace vehicle plume dataset was preprocessed through characteristic parameter extraction, extended physical parameter calculation, data splicing and sliding window operation, and the LSTM network structure was optimized by adjusting hyperparameters such as the number of hidden layers and neurons. Experimental results show that the proposed algorithm achieves a Mean Absolute Error (MAE) of 31.89 and a Physical Inconsistency of 0.1723 on the test set, with MAE reduced by 14% and Physical Inconsistency reduced by 7.5% compared with traditional machine learning models such as Random Forest. Ablation experiments verify that the introduction of physical mechanisms can improve the prediction accuracy of the model by about 25%. This algorithm makes up for the defects of traditional prediction algorithms, has good generalization ability and physical consistency, and provides an effective method for the prediction of engine exhaust plume temperature distribution. Full article

Orbital maneuver detection is a core component of space situational awareness. The multi-scale characteristics of satellite orbital behavior and sample imbalance issues lead to challenges in existing methods, including insufficient feature adaptation and limited detection accuracy. This paper proposes an Adaptive Spiking Gating Multi-Scale Liquid State Machine (ASG-MSLSM) for orbital maneuver detection based on variations in satellite orbital parameters. The method integrates multi-scale reservoir pools with different scale-dependent decay factors and Leaky Integrate-and-Fire (LIF) neurons to enhance multi-scale temporal feature extraction capability. A spiking gating network is designed to adaptively learn fusion weights for multi-scale features, replacing traditional fixed equal-weight fusion strategies. During training, weighted binary cross-entropy loss is employed to address class imbalance. Experimental results based on real satellite data demonstrate that the proposed method significantly outperforms baseline models in maneuver detection metrics, achieving higher recall, improving feature separability, and reducing both missed detections and false alarms. These results indicate that the proposed method provides a robust solution for orbital maneuver detection. Full article

Manganese (Mn) is an essential trace element crucial for antioxidant defense, metabolism, and neuronal function, yet both deficiency and excess may induce oxidative stress and organ-specific damage. This study investigated the effects of dietary manganese exclusion and replacement of standard MnCO₃ with Mn₂O₃ nanoparticles on redox status and oxidative damage in rats. Twenty-four male Wistar rats were divided into three groups: control (K) receiving 65 mg/kg Mn as MnCO₃, manganese-deficient (B), and nanoparticle-supplemented (N) receiving 65 mg/kg Mn as Mn₂O₃ nanoparticles. After 12 weeks, tissues were analyzed for oxidative stress markers and antioxidant enzyme activities. Manganese deficiency resulted in decreased plasma SOD activity, increased lipid peroxidation, and severe oxidative–nitrosative damage in the brain and jejunum, despite hepatic compensatory mechanisms. Mn₂O₃ nanoparticle supplementation enhanced hepatic and renal antioxidant capacity, reducing oxidative damage in these organs. However, nanoparticles induced pronounced neurotoxicity, characterized by GSH depletion, elevated DNA damage (8-OHdG), protein nitration (3-NT), and caspase activation in brain tissue. These findings demonstrate that while Mn₂O₃ nanoparticles offer improved bioavailability and hepatorenal benefits, they pose significant neurotoxic risks, necessitating caution in dietary supplementation strategies. Full article

Air pollution is a growing hazard to global health. Epidemiological studies have reported a potential role of air pollutant exposure in the development or aggravation of neurodegenerative diseases. However, the underlying mechanisms are ill-defined. Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of cell death that drives neuronal loss in neurodegenerative diseases. Our previous studies reported the involvement of adenosine 3′,5′-cyclic monophosphate (cAMP) and EPAC (exchange protein directly activated by cAMP) in ferroptotic cell death. Here, we investigated the effects of diesel exhaust particles (DEP) in mouse hippocampal (HT22) neuronal cells. Our data showed that toxicity induced by RSL3 (50–75 nM), a ferroptosis inducer, was significantly increased by the addition of DEP (100 μg/mL). Pharmacological inhibition of EPAC1 (CE3F4 30 μM or AM-001 30 μM) and soluble adenylyl cyclase (sAC; TDI-10229 1 μM or TDI-11861 0.1 μM) prevented enhanced ferroptotic HT22 cell death caused by DEP, while pharmacological modulation of EPAC2, protein kinase A (PKA), phosphodiesterases (PDEs), or transmembrane AC did not. DEP in combination with RSL3 exposure increased intracellular calcium levels and induced lysosomal de-acidification. Furthermore, inhibition of EPAC1 prevented mitochondrial ROS (MitoSOX) and lipid peroxidation (BODIPY C11 and MDA levels) after DEP and RSL3 co-exposure. Collectively, EPAC1 may serve as a novel target for the treatment or prevention of neurodegenerative diseases accelerated by air pollution. Full article

Predictive modeling using artificial neural networks (ANN) has drawn a lot of interest as a quick, dependable, and non-destructive method for assessing food qualities. In order to forecast the thermal conductivity and thermal diffusivity of a beverage made from buttermilk sweetened with date syrup from the Khlass type, this study developed an ANN model. We looked into the effects of date syrup concentration (5,10, and 15%), storage cooling temperature (0, 5,10, 15 °C), and storage duration (0,3,6,9,12, and15 days). The findings of the experiment showed that while higher date syrup concentrations and storage temperatures led to higher values of these attributes, longer storage times decreased both thermal conductivity and thermal diffusivity. Thermal diffusivity was between 1.317 × 10⁻⁷ and 2.247 × 10⁻⁷ m²/s, while thermal conductivity was between 0.533 and 0.632 W/m K. Using a trial-and-error method, the best ANN architecture was found to include three input neurons, one hidden layer with twenty neurons, and two output neurons. With mean absolute errors of 1.80 × 10⁻³ W/m K and 1.7 × 10⁻⁹ m²/s for thermal conductivity and thermal diffusivity, respectively, using the testing points, the model shows excellent forecast accuracy. According to sensitivity analysis, the most significant factor influencing both thermal properties was storage duration. Full article

Neurodegenerative diseases, characterized by progressive neuronal loss and functional decline, impose a substantial global health burden. Autophagy, the principal intracellular degradative pathway for clearing misfolded proteins and damaged organelles, is vital for neuronal homeostasis, whereas maladaptive neuroinflammation is increasingly being recognized as a central driver of disease progression. A growing body of evidence indicates a bidirectional, tightly coupled relationship between autophagy and neuroinflammation: impaired autophagic flux promotes accumulation of damage-associated molecules that activate innate immune responses, while sustained inflammatory signaling further disrupts autophagy, together forming a self-reinforcing cycle that accelerates neurodegeneration. This interplay is regulated by diverse genetic, molecular, cellular, and environmental factors and manifests in cell-type-specific ways across microglia, astrocytes. Therapeutic strategies emerging from these insights include modulation of autophagic pathways (e.g., mTOR, AMPK, TFEB), targeted inhibition of inflammasome and pro-inflammatory mediators (notably NLRP3-related signaling), and delivery platforms for small molecules or nucleic acids, with increasing interest in multi-target and stage-specific interventions. This review integrates mechanistic evidence and translational advances, highlights gaps in cell-type and stage-specific understanding, and outlines priorities for developing safe, effective therapies that target the autophagy–neuroinflammation axis in neurodegenerative disorders. Full article

Extracellular vesicles (EVs) are nanoscale membrane-bound particles that mediate intercellular communication by transferring proteins, nucleic acids, lipids, and metabolites. Increasing evidence implicates EVs in Alzheimer’s disease (AD) pathogenesis through the propagation of amyloid-β, tau, and neuroinflammatory signals across neural and glial networks. In parallel, EVs isolated from biofluids have emerged as promising sources of disease-associated biomarkers and potential therapeutic carriers. This review aims to synthesize current evidence on EV-mediated mechanisms in AD, evaluate the diagnostic value of EV-associated biomarkers, and discuss emerging EV-based and bioengineered therapeutic strategies. We summarize how EVs derived from neurons, astrocytes, microglia, and peripheral cells contribute to amyloid-β and tau spread, neuroinflammation, synaptic dysfunction, and metabolic stress in AD. Disease-associated alterations in EV cargo from blood, cerebrospinal fluid, and urine are critically assessed for biomarker applications. We further highlight advances in EV bioengineering, including cargo loading, surface modification, targeting strategies, and modulation of EV biogenesis. Finally, key translational challenges—such as EV heterogeneity, biodistribution, immune clearance, and standardization—are discussed to define future directions for leveraging EVs as diagnostic and therapeutic platforms in AD. Full article

Neurodegenerative disorders, including Parkinson’s disease (PD), are largely treated with symptomatic therapies, underscoring the need for strategies that target underlying disease mechanisms. Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R), a class B G protein-coupled receptor best known for metabolic regulation, have attracted interest due to the increasing evidence of central nervous system (CNS) actions. This review synthesises mechanistic, preclinical, and clinical evidence examining GLP-1R signalling in PD and related neurodegenerative contexts. We integrate findings from cellular and animal models with early-phase clinical studies of GLP-1 receptor agonists (GLP-1RAs). Across experimental systems, GLP-1R activation engages conserved intracellular pathways—cAMP/PKA, PI3K/Akt, and ERK—that regulate mitochondrial function, oxidative stress, autophagy-lysosomal dynamics, and inflammatory signalling. In PD-relevant models, these pathways intersect with key pathogenic features, including α-synuclein accumulation, dopaminergic neuron vulnerability, and glial reactivity. Clinical studies to date demonstrate acceptable safety and tolerability, alongside biomarker evidence of central pathway engagement and variable effects on motor and non-motor outcomes. However, uncertainties remain regarding CNS target engagement, peripheral versus CNS mechanisms, and disease-stage dependence. Overall, the current evidence positions GLP-1R signalling as a biologically plausible therapeutic pathway in PD that warrants further mechanistic clarification and rigorous evaluation in ongoing and future clinical trials. Full article

Background/Objectives: Snow Chrysanthemum (Coreopsis tinctoria Nutt.), a traditional medicinal and edible plant rich in flavonoids (TFSC) with antihypertensive and neuroprotective activities, has unclear effects and mechanisms on vascular dementia (VaD) comorbid with hypertension, a key risk factor accelerating VaD. This study aimed to investigate TFSC’s ameliorative effects on cognitive impairment in hypertensive VaD rats and elucidate its holistic therapeutic mechanisms. Methods: Spontaneously hypertensive rats (SHRs) with unilateral common carotid artery ligation were used to establish the hypertensive VaD model. TFSC was intragastrically administered for 11 weeks. Systolic blood pressure (BP) and cerebral blood flow (CBF) were monitored; cognitive function was assessed via open field, novel object recognition and Morris water maze tests. Histopathological changes were evaluated by H&E and Nissl staining, serum oxidative stress and inflammatory markers were measured, and hippocampal transcriptome sequencing plus RT-qPCR was performed to identify key pathways and genes. Results: The chemical profile of TFSC was characterized, showing a total flavonoid content of 84.96%; 49 compounds were identified, 39 of which were flavonoids. TFSC reduced BP, improved CBF, alleviated cognitive dysfunction and neuronal damage, enhanced antioxidant capacity (increased SOD, CAT, GSH; decreased ROS), and exerted anti-inflammatory effects (reduced TNF-α, IL-1β, IL-6, Ang-II). It modulated multiple pathways, with the PI3K-Akt and MAPK pathways enriched, and validated key differentially expressed genes. Conclusions: This study provides preliminary evidence for the holistic therapeutic potential of TFSC against hypertensive VaD. With integrated vascular regulatory and neuroprotective effects, TFSC serves as a promising candidate for VaD by targeting both vascular risk factors and neuropathological damage. Full article

Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin receptor kinase B (TrkB) are classically associated with neuroplasticity, but increasing evidence suggests a broader role for BDNF/TrkB signaling in systemic stress adaptation beyond the central nervous system. Strenuous exercise is a model of functional stress that may become a clinically relevant renal challenge under conditions such as dehydration, heat stress, vascular vulnerability, and repeated exposure. Neuroendocrine stress activation, hemodynamic perturbations, and cytoskeletal instability are key factors that may contribute to glomerular barrier dysfunction in this setting. BDNF biogenesis is complex, and circulating BDNF largely reflects platelet-associated pools and context-dependent release. At the tissue level, BDNF/TrkB signaling can activate actin-regulatory pathways involved in cellular resilience. The podocyte is of particular interest because its actin-dependent architecture functionally parallels that of neurons and is essential for maintenance of the glomerular filtration barrier. Within this framework, BDNF/TrkB signaling may stabilize podocyte actin dynamics, reduce foot process effacement, and attenuate proteinuria. The present review focuses on the brain–kidney axis and the potential renoprotective role of BDNF/TrkB signaling, while highlighting major knowledge gaps regarding BDNF availability to glomerular cells, isoform-specific TrkB actions, and causal inference in humans exposed to repeated exercise-related renal stress. However, current human evidence is insufficient to define the dominant source and delivery route of BDNF to glomerular cells during exercise-related renal stress. Therefore, BDNF/TrkB is discussed here as a candidate modulatory/resilience pathway rather than an established causal driver. Full article