Search Results (1,786)

Advances in multimodal therapy for high-risk neuroblastomas (NBs) have plateaued, prompting therapeutic initiatives to harness the immune system. NBs, however, are immunologically “cold” and a significant challenge to immunotherapy. Here, in a Jurkat lymphocyte cytotoxicity model, we describe an antigen-independent, cell-mediated mechanism for eliminating NB cells, first detected in PMA-activated low pcDNA-SH-SY5Y and high TrkAIII-SH-SY5Y TrkAIII-expressing cells, which are resistant to Jurkat elimination under normal conditions. Characterization of this mechanism through live cell imaging, adhesion assays, RT-PCR, Western blotting and indirect IF, employing a variety of inhibitors, indicates that it initiates with PMA-induced NB cell CCL2 expression. This results in CCL2 promotion of Jurkat CCR2b expression, CCL2/CCR2b-mediated Jurkat LFA-1 activation and the formation of cytotoxic lipid-raft LFA1/ICAM-1 immune synapses, through which Jurkat m-TRAIL combines with PMA-enhanced NB cell DR5/TRAIL-R2 expression to induce NB cell apoptosis. This mechanism is enhanced by the NB-associated oncoprotein TrkAIII through Shp/Src-regulated c-FLIP sequester and is PD-L1/PD-1-independent and resistant to osteoprotegerin. It eliminates both non-MYCN-amplified (SH-SY5Y and SK-N-SH) and MYCN-amplified (SMS-KCNR) NB cells that exhibit PMA-inducible CCL2 expression but not MYCN-amplified NB cells (IMR-32 and NB-1) that exhibit CCL2 repression, and is offset by reciprocal NB cell-induced Fas-mediated Jurkat cell apoptosis. These findings form a solid foundation for further pre-clinical development aimed at identifying clinically relevant physiological immune cell equivalents and alternative PKC activators, with the ultimate goal of translating this mechanism into an effective immune-therapeutic approach for the treatment of high-risk non-immunogenic NBs, especially NBs that exhibit CCL2 and TrkAIII expression. 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

Medical image segmentation is essential for clinical decision-making, treatment planning, and disease monitoring. However, ambiguous boundaries and complex anatomical structures continue to pose challenges for accurate segmentation. To address these issues, we propose DCANet (Disentangled and Category-Aware Network), a novel framework that effectively integrates local and global feature representations while enhancing category-aware feature interactions. In DCANet, features from convolutional and Transformer layers are fused using the Feature Coupling Unit (FCU), which aligns and combines local and global information across multiple semantic levels. The Decoupled Feature Module (DFM) then separates high-level representations into multi-class foreground and background features, improving discriminability and mitigating boundary ambiguity. Finally, the Category-Aware Integration Aggregator (CAIA) guides multi-level feature fusion, emphasizes critical regions, and refines segmentation boundaries. Extensive experiments on four public datasets—Synapse, ACDC, GlaS, and MoNuSeg—demonstrate the superior performance of DCANet, achieving Dice scores of 84.80%, 94.07%, 94.60%, and 79.85%, respectively. These results confirm the effectiveness and generalizability of DCANet in accurately segmenting complex anatomical structures and resolving boundary ambiguities across diverse medical image segmentation tasks. Full article

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, for which aging represents the main risk factor. As the global elderly population expands, the prevalence of Alzheimer’s disease escalates rapidly. Notably, as AD brain lesions may start 15–20 years before the appearance of the first symptoms, early diagnosis or prognosis of AD is of paramount importance for better patient treatment. Based on the absence of effective cure or early diagnosis of AD, this meta-analysis investigates the differentially expressed genes between Alzheimer’s and a healthy brain and identifies genes that can serve as risk factors for the disease or biomarkers of diagnostic, prognostic, or pharmacological value. Microarray datasets were collected from public repositories, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Quality control and data normalization were performed. Differentially expressed gene (DEG) lists were created for each study and combined through a Mosteller–Bush meta-analysis, resulting in a final list of DEGs. This list was filtered using an adjusted p-value cut-off of 0.001, and the included statistically significant DEGs were subjected to enrichment analyses. A total of eight microarray studies were identified, producing a combined list of 4218 DEGs, of which 1944 were up-regulated and enriched for immune response processes, and 2274 were down-regulated and enriched for synapse-related pathways. This meta-analysis reveals a distinct transcriptomic profile in Alzheimer’s disease characterized by the prevalence of immune response and inflammation alongside the collapse of essential synaptic and neuronal signaling. Full article

Spin–orbit torque (SOT)-based spintronic devices have emerged as a preferred candidate for next-generation artificial synaptic devices due to their advantages of non-volatility, high speed, and low power consumption. The development of high-performance SOT-based artificial synaptic devices relies on the breakthrough in SOT-driven magnetization switching, wherein the performance regulation and structural design of the magnetic layer are the core critical factors. In this work, the Co/Ho multilayer system is employed as the magnetic layer to investigate its SOT-driven magnetization switching characteristics and application potential in artificial synapses. By regulating the periodic parameters of the Co/Ho multilayer structure, high perpendicular magnetic anisotropy (PMA) can be stably maintained in devices with relatively thick ferrimagnetic layers. Moreover, we elucidate the role of the antiferromagnetic coupling interface between Co and Ho in the multilayer structure in enhancing SOT efficiency and demonstrate the achievement of a high spin Hall angle of up to 0.22. The high SOT efficiency of the system enables it to drive the 8.4 nm-thick magnetic layer to achieve highly stable magnetization switching. Multistate magnetization switching behavior is observed, which can be used to simulate synaptic weight updates in neuromorphic networks, demonstrating the broad application prospects of this system in the field of artificial neural networks. Full article

All-optical memristors possess light-sensing and storage capabilities while simultaneously simulating human synaptic functions, demonstrating immense potential in the field of brain-inspired computing for realizing bionic synapses and brain-like intelligence. In this work, we successfully produced ε-Ga₂O₃ films, ε/β-Ga₂O₃ mixed-phase films, and β-Ga₂O₃ films via chemical vapor deposition (CVD). The optical output and optical response characteristics of the thin films are investigated under 254 nm and 365 nm lasers. The CVD-grown ε-Ga₂O₃ is found to process a small amount of defects and insignificant memristive properties and the β-Ga₂O₃ obtained from the annealing of ε-Ga₂O₃ exhibits superior crystal quality but lacks memristive properties, while the ε/β-Ga₂O₃ mixed-phase films grown directly by CVD contain a fair amount of defects and demonstrate persistent resistance retention exceeding 104 s. Based on the excellent memristive properties of ε/β-Ga₂O₃ mixed-phase films, we conducted experiments simulating optical synapses. By adjusting optical pulse parameters (intensity, repetition rate, and duration), we successfully modeled the short-term plasticity (STP) and long-term plasticity (LTP) observed in biological synapses. Experiments confirm that light stimulation can effectively induce synaptic behaviors, such as the progressive conversion of short-term memory (STM) into long-term memory (LTM), and further fully reproduce the neuroplasticity process of “learning-forgetting-relearning.” This study demonstrates a photoconductive synapse memristor based on the wide-bandgap material gallium oxide, exhibiting exceptional air stability with sustained photoconductivity maintained for over a year. This study provides new insights into the practical application feasibility of all-optical artificial synapses based on gallium oxide. Full article

This study presents the development of a Nervous System-on-Chip (NoC) using microfabrication techniques, focusing on the integration of human induced pluripotent stem cell (hiPSC)-derived neurons. We designed and fabricated NoCs based on microtunnel devices (MDs) with radial and linear configurations to facilitate the compartmentalized culture of cortical and enteric neural networks. Our findings demonstrate that these MDs allow axonal growth while restricting migration of somas and dendrites between compartments, thereby promoting the formation of organized neural networks. This creates a microfluidic platform capable of supporting the growth of different culture systems, which could potentially be combined to study interactions between the central and enteric nervous systems. The resulting neuronal networks exhibited viability, expression of key lineage markers, and synapse formation, highlighting the platform’s potential for advanced nervous system modeling. MD-based NoC models provide an innovative microfluidic platform for studying the biology of human neural networks, with implications for the investigation of neurodegenerative diseases such as Parkinson’s Disease and applications in pre-clinical research. Full article

The memristor has long been known as a nonvolatile memory technology alternative and has recently been explored for neuromorphic computing, owing to its capability to mimic the synaptic plasticity of the human brain. The architecture of a memristor synapse device allows ultra-high-density integration by internetworking with crossbar arrays, which benefits large-scale training and learning using advanced machine-learning algorithms. In this review, we present a statistical analysis of neuromorphic computing device publications from 2018 to 2025, focusing on various memristive systems. Furthermore, we provide a device-level perspective on biomimetic properties in hardware neural networks such as short-term plasticity (STP), long-term plasticity (LTP), spike timing-dependent plasticity (STDP), and spike rate-dependent plasticity (SRDP). Herein, we highlight the utilization of optoelectronic synapses based on 2D materials driven by a sequence of optical stimuli to mimic the plasticity of the human brain, further broadening the scope of memristor controllability by optical stimulation. We also highlight practical applications ranging from MNIST dataset recognition to hardware-based pattern recognition and explore future directions for memristor synapses in healthcare, including artificial cognitive retinal implants, vital organ interfaces, artificial vision systems, and physiological signal anomaly detection. Full article

This paper addresses the opportunities and risks of integrating Large Language Models (LLMs) into structural engineering. Exclusive reliance on LLMs is inadequate in this field, because their probabilistic nature can lead to hallucinations and inaccuracies that are unacceptable in safety-critical domains which require rigorous calculations. To resolve this dilemma, we propose adopting Neuro-Symbolic Artificial Intelligence (NSAI), a hybrid approach that balances neural intuition with symbolic rigor. The NSAI architecture employs an intelligent query system to enrich user requests and delegate critical operations to deterministic external algorithms. This system is designed to enhance reliability and support regulatory compliance, as exemplified by the 3Muri chatbot case study, an NSAI (gemini-2.5-flash)-based intelligent assistant for structural analysis software. We developed 3Muri chatbot implementing AI processes. Our experimental results, based on over 200 questions submitted to the chatbot, show that this hybrid approach achieves 94% accuracy while keeping response times below 2 s. These results validate the feasibility of deploying AI systems in safety-critical engineering domains. Full article

Tunneling nanotubes (TNTs) are dynamic cell surface conduits that enable direct transfer of ions, signaling molecules, and organelles. They have emerged as a key mechanism of intercellular communication, complementing classical pathways such as synapses and paracrine signaling. In the central nervous system (CNS), TNTs exhibit a functional duality, particularly under aging and stress, where TNT-mediated exchange may shift from protective to maladaptive. On one hand, TNTs support homeostatic functions, ranging from mitochondrial transfer to stem cell-mediated rescue and astrocyte–neuron metabolic support. On the other hand, they facilitate the spread of prions and neurodegenerative protein aggregates, such as Tau and α-synuclein, with astrocytes playing a regulatory role. Despite rapid advances, TNT research faces challenges from conceptual heterogeneity and experimental standardization, especially in complex tissues such as the CNS. Recent mechanobiological and bio-inspired approaches, including force-based assays and three-dimensional culture models, provide new insights into TNT formation, stability, and cargo transport, extending beyond neural systems. This review offers an integrative synthesis of molecular, structural, and mechanobiological principles underlying TNT-mediated communication, emphasizing astrocyte–neuron crosstalk, while proposing validation criteria to support rigor, reproducibility, and cross-study comparability. TNTs thus emerge as dynamic, context-dependent interfaces with broad relevance to neurodegeneration, cancer, and biomedical applications. Full article

Neuromuscular junctions (NMJs) are highly specialized synapses that enable efficient communication between motor neurons and skeletal muscle fibers. Impaired formation or maintenance of NMJs is implicated in the pathogenesis of multiple neuromuscular disorders and contributes to age-related declines in skeletal muscle mass and strength. NMJ functionality is governed by complex regulatory crosstalk among different cells and is mediated by a diverse network of proteins. Moreover, immune cells often reside at NMJs and exhibit phenotypically different characteristics depending on the regenerative state of the muscle. These complex interfaces have posed a significant challenge for elucidating pathogenic mechanisms and developing biomarkers or effective targeted treatments. Many animal models have been developed to address this challenge by characterizing the fundamental structural features of neuromuscular junctions (NMJs) and their transmission capacity under both healthy and disease conditions. In contrast, studies of human NMJs remain limited, although emerging evidence is increasingly revealing substantial morphological and functional differences from animal NMJs. This review provides an overview of animal research on NMJs over the past decades, highlighting interspecies differences and key advances in our understanding of human NMJs. Full article

Background/Objectives: Injuries to spinal ventral roots induce complex retrograde reactions that compromise motoneuron survival, synaptic organization, and glial responses, ultimately limiting the potential for regeneration. The endocannabinoid system (ECS) has emerged as a crucial modulator of neuroprotective processes, primarily through the activation of CB1 and CB2. However, the individual and combined contributions of these receptors to post-injury spinal responses remain poorly understood. Here, we examined the effects of selective blockade of CB1 and CB2 receptors in a murine model of ventral root crush (VRC). Methods: Female C57BL/6JUnib mice received daily intraperitoneal injections of the CB1 antagonist AM-251 and/or the CB2 antagonist AM-630 (1 mg/kg) for 14 days post-lesion. At 28 days after injury, spinal cords were analyzed for motoneuron survival (Nissl staining), glial responses (immunohistochemistry for GFAP and Iba-1), and synaptic coverage (immunohistochemistry for synaptophysin). Results: Selective blockade of CB2 receptors led to a marked reduction in motoneuron survival, enhanced microglial activation-associated morphology (morphological classification and Sholl analysis), and decreased synaptic coverage. CB1 blockade produced milder, context-dependent effects. Dual blockade exacerbated all outcomes, indicating complementary CB1/CB2 functions in the spinal microenvironment. Conclusions: Under the conditions tested, CB2 signaling is necessary for motoneuron preservation, limiting microglial activation-associated morphology, and maintaining synaptic coverage after VRC. The knowledge of specific actions of CB1 and CB2 provides mechanistic insight into the neuroprotective potential of endocannabinoid signaling and reinforces its therapeutic relevance for motoneuron preservation and functional recovery after axotomy. Full article

Mitochondrial Ca²⁺ signaling is increasingly recognized as a key integrator of synaptic activity, metabolism, and redox balance within the tripartite synapse. At excitatory synapses, Ca²⁺ influx through ionotropic glutamate receptors and voltage-gated channels is sensed and transduced by strategically positioned mitochondria, whose Ca²⁺ uptake and release tune tricarboxylic acid cycle activity, adenosine triphosphate synthesis, and reactive oxygen species (ROS) generation. Through these Ca²⁺-dependent processes, mitochondria are proposed to help set the threshold at which glutamatergic activity supports synaptic plasticity and homeostasis or, instead, drives hyperexcitability and excitotoxic stress. Here, we synthesize how mitochondrial Ca²⁺ dynamics in presynaptic terminals, postsynaptic spines, and perisynaptic astrocytic processes regulate glutamate uptake, recycling, and release, and how subtle impairments in these pathways may prime synapses for failure well before overt energetic collapse. We further examine the reciprocal interplay between Ca²⁺-dependent metabolic adaptations and glutamate homeostasis, the crosstalk between mitochondrial Ca²⁺ and ROS signals, and the distinct vulnerabilities of neuronal and astrocytic mitochondria. Finally, we discuss how disruption of this Ca²⁺-centered mitochondria–glutamatergic axis contributes to synaptic dysfunction and circuit vulnerability in neurodegenerative diseases, with a particular focus on Alzheimer’s disease. Full article

Whole-genome bisulfite sequencing (WGBS) was employed in this article to map blood DNA methylation profiles at single-base resolution in Yili horses before a 5000 m speed race, with comparative analysis of epigenetic differences between the ‘elite group’ and ‘ordinary group’ across six four-year-old stallions. The overall methylation level in the elite group was generally higher than that in the ordinary groups, with a minority of regions showing hypomethylation. For instance, the promoter regions of key metabolic and neuro-related genes exhibited significant hypomethylation. The article identified over 10,000 CG differential methylation regions (DMRs), predominantly enriched in promoter and CpG island regions, anchoring 7221 differentially methylated genes (DMGs). These DMGs were significantly enriched in key biological processes including oxidative phosphorylation, protein binding, axon guidance, glutamatergic synapses, and the Hedgehog signalling pathway. Among these, six genes—ACTN3, MSTN, FOXO1, PPARGC1A, ND1, and ND2—were selected as core candidate genes closely associated with muscle strength, energy metabolism, and stress adaptation. The study confirms that the differences in athletic ability among Yili horses have a significant epigenetic basis, with DNA methylation participating in the epigenetic regulation of athletic traits by modulating the expression of genes related to energy metabolism and neuroplasticity. The constructed “promoter hypomethylated DMR panel” holds promise for translation into non-invasive blood-based epigenetic markers for early performance evaluation and targeted breeding in racehorses. This provides a theoretical basis and molecular targets for improving equine athletic phenotypes and optimising training strategies. Full article

Neuromechanobiology has emerged as a multidisciplinary field at the interface of neuroscience and mechanobiology, aiming to elucidate how mechanical forces influence the development, organization, and function of the nervous system. This review offers a comprehensive overview of the historical evolution of the discipline, its molecular and biophysical foundations, and the experimental strategies employed to investigate it. Recent advances have revealed the pivotal roles of substrate stiffness, mechanical signaling, and force transduction in neural stem proliferation, axon guidance, synapse formation, and neural circuit maturation. All these effects originate at the molecular level and extend to the mesoscopic scale. Disrupted mechanotransduction has been increasingly implicated in neurodevelopmental disorders and neurodegenerative diseases, underscoring its clinical relevance. Key unresolved questions and future directions are also highlighted, with emphasis on the need for integrative approaches to decipher the complex interplay between mechanical forces and neural function. Full article