Search Results (349)

The neuroendocrine and immune systems interact bidirectionally through shared ligands and receptors during inflammation, thereby regulating immune responses. Leptin, primarily known for its role in energy metabolism and appetite regulation, also modulates neuroinflammatory pathways. Its receptors are widely expressed on immune cells and contribute to immune mechanisms implicated in the pathogenesis of neuroinflammatory disorders such as multiple sclerosis (MS) and Alzheimer’s disease (AD). This review highlights recent advances in understanding leptin’s role in immune regulation, with a focus on its impact on MS and AD. A comprehensive literature review was conducted until October 2025, using PubMed, Google Scholar, and Scopus to identify studies investigating leptin in neuroinflammatory conditions, particularly MS and AD. Leptin exerts broad immunomodulatory effects by activating T cells, dendritic cells, and microglia, and promoting their proliferation and phagocytosis. Its elevation enhances Th1 and Th17 responses, drives pro-inflammatory macrophage phenotype polarization, and suppresses regulatory T cell and Th2 responses, immune pathways involved in MS. Peripheral leptin levels are increased in MS, especially during disease exacerbations. In contrast, in AD, they are typically reduced, particularly in patients with normal body mass index (BMI), where their decline contributes to amyloid-β and tau pathology. These divergent patterns position leptin as a bidirectional regulator at the intersection of immunity and neurodegeneration. Additionally, its protective or detrimental effects likely depend on whether it acts under physiological conditions or in the context of obesity-induced leptin resistance. Elevated leptin levels in obesity exacerbate inflammation and diminish its neuroprotective effects. In conclusion, leptin is elevated in MS patients but downregulated in AD, reflecting its bidirectional effects. In leptin resistance, peripheral proinflammatory signaling is maintained while central leptin signaling is restricted, thereby potentially promoting autoimmunity in MS and limiting neuroprotection in AD. Further mechanistic and longitudinal studies are needed to clarify the relationship between leptin dysregulation, leptin resistance, neuroinflammatory and neurodegenerative diseases. Full article

Neuropathic pain represents a critical challenge in medical research and clinical practice. Enhanced peripheral nerve activity and spinal dorsal horn neuronal firing are thought to contribute to the nociceptive hypersensitivities that are observed in chronic pain conditions, including those modeled by partial sciatic nerve ligation (PSNL). However, the detailed in vivo neuronal response dynamics and underlying mechanisms in the PSNL model remain to be fully clarified. To better understand these mechanisms, we evaluated dorsal root ganglion (DRG) and spinal dorsal horn neuronal activity in the PSNL model using in vivo approaches. Von Frey testing revealed sustained mechanical allodynia in PSNL animals; withdrawal thresholds were significantly reduced up to day 14 post-surgery. Immunohistochemistry revealed a stimulation-dependent increase in phosphorylated extracellular signal-regulated kinase (pERK)-positive neurons in the DRG, thereby indicating heightened peripheral nerve activity. Additionally, electrophysiological recordings demonstrated the enhanced firing of spinal dorsal horn neurons in response to the same stimuli. Notably, DRG pERK expression changes correlated with spinal neuronal firing frequency. Together, these findings suggest that peripheral nerve activity drives spinal neuronal sensitization, thus elucidating both pain mechanisms in the PSNL model and activity-dependent signaling in neuropathic pain. Full article

Hericium erinaceus is a medicinal mushroom valued in the wellness industry for its neuroprotective, immunomodulatory, and antioxidant activities. While many extracts and bioactive compounds from both mycelium and fruit bodies have been characterized, the mechanisms driving their effects are not fully understood. Here, the transcriptomic and protein-level effects of H. erinaceus mycelium (HDLM) in human peripheral blood mononuclear cells (PBMCs) were investigated, along with antioxidant and iron chelating activity. A commercially available H. erinaceus fruit body extract (FBE) claiming high β-glucan content was included in a subset of assays to compare immune-related outcomes between mycelial and fruit body constituents. HDLM activated a wide array of immune- and oxidative stress-related transcripts and pathways, exhibited significant antioxidant activity, and consistently reduced IL-1β, TNF-α, and IL-8 during LPS challenge while maintaining low basal cytokine expression, indicating targeted immunomodulatory activity. FBE almost doubled production of IL-1β when challenged by LPS, whereas HDLM significantly decreased production of this stress mediator. HDLM also demonstrated augmented iron chelating ability when compared to FBE. Depending on tissue source and preparation methods, different H. erinaceus materials may either potentiate or quench stress responses, highlighting the need for further bioactivity and safety comparisons across H. erinaceus supplements, particularly with respect to cytokine regulation under conditions of immune challenge. Full article

Spatial cognition is fundamental to an animal’s ability to move through and interact with its environment. Thus, understanding the physiological basis for this cognitive function and how it varies across taxa is fundamental to understanding how ecology alters brain architecture and function. Although elements of spatial cognition can be found across the animal kingdom, here we concentrate specifically on cognitive maps and their physiological basis. This will begin with a focus on the rodent model, which is the source of the vast majority of data on the neural basis of cognitive maps. This serves as a foundation for comparative analysis of other taxa to demonstrate that, although this line of inquiry is relatively new and small, important variations have been observed, tied largely to changes in both perception and ambulation, that may fundamentally alter how spatial cognition is implemented. This latter analysis emphasizes birds, as recent data in this order provide fundamental insights into how the selective pressures that drive changes in peripheral physiology also drive commensurate neuronal changes in spatial cognition. Full article

Innovation in the new energy industry serves not only as a key accelerator for the global green and low-carbon energy transition but also as a core driving force of the ongoing energy revolution. This study utilizes data on publications, patents, and the spatial distribution of representative innovation enterprises in the new energy industry of the Yangtze River Delta urban agglomeration from 2009 to 2023 to construct a multilayer science–technology–industry innovation network. Social network analysis is employed to examine its evolutionary dynamics and structural characteristics, and the Quadratic Assignment Procedure (QAP) is used to investigate the factors shaping intercity innovation linkages. The results reveal that the multilayer innovation network has continuously expanded in scale, gradually forming a multi-core radiative structure with Shanghai, Nanjing, and Hangzhou at the center. At the cohesive subgroup level, the scientific and technological layers exhibit clear hierarchical differentiation, where core cities tend to engage in strong mutual collaborations, while the industrial layer shows a hub-and-spoke pattern combining large, medium, and small cities. In terms of layer relationships, the centrality of the scientific layer increasingly surpasses that of the technological and industrial layers. Inter-layer degree correlations and overlaps also display a strengthening trend. Furthermore, differences in regional higher education scale, urban economic density, and geographic proximity are found to exert significant influences on scientific, technological, and industrial innovation linkages among cities. In response, this study recommends enhancing the leadership role of core cities, leveraging the bridging and intermediary functions of peripheral cities, and promoting application-driven cross-regional innovation collaboration, thereby building efficient science–technology–industry networks and enhancing intercity innovation linkages and the flow of innovation resources, and ultimately promoting the high-quality development of the regional new energy industry. Full article

Neurofibromatosis type 1 (NF1) predisposes to a spectrum of peripheral nerve sheath tumors, ranging from benign plexiform neurofibromas (PN) to atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP) and malignant peripheral nerve sheath tumors (MPNST). Tumorigenesis follows a multistep molecular cascade initiated by biallelic NF1 inactivation, followed by CDKN2A loss and disruption of the Polycomb Repressive Complex 2 (PRC2). These events guide chromatin remodeling, widespread epigenetic dysregulation, and activation of oncogenic pathways such as RAS/MAPK and PI3K/AKT. Here, we integrate genomic, transcriptomic, and epigenomic studies to delineate the molecular trajectories underlying tumor progression and to define promising biomarkers for the early detection of malignant transformation. Emerging liquid biopsy approaches, based on circulating tumor DNA (ctDNA) analyses, reveal distinctive copy number variations (CNVs) and methylation patterns that mirror tissue-derived profiles, enabling the detection of malignant transformation. Together, these findings support a model in which cumulative genetic and epigenetic alterations drive the PN–ANNUBP–MPNST continuum. They also underscore the value of multi-omics and liquid biopsy-based strategies to improve early diagnosis, patient risk stratification, and personalized management of NF1-associated tumors, thereby advancing precision medicine in this complex disease spectrum. Full article

We present the first aero-structural evaluation of a 3 m-diameter hybrid wind-PV rotor employing flat-plate blades stiffened by a peripheral ring. Owing to the lack of prior data, we combine low-Reynolds BEM, elastic FEM sizing, and steady-state CFD (k-ω SST) to build a coherent preliminary load and performance dataset. After upsizing the hub pins (Ø 30 mm), ring (50 × 50 mm) and spokes (Ø 40 mm), von Mises stresses stay below 25% of the 6061-T6 yield limit and tip deflection remains within 0.5% R across Cut-in (3 m/s), Nominal (5 m/s) and Extreme (25 m/s) wind cases. CFD confirms a flat efficiency plateau at λ = 2.4–2.8 (β = 10°) and zero braking torque at β = 90°, validating a three-step pitch schedule (20° start-up → 10° nominal → 90° storm). The study addresses only the rotor; off-the-shelf generator, brake, screw-pitch and azimuth/tilt drives will be integrated later. These findings set a solid baseline for full-scale testing and future transient CFD/FEM iterations. Full article

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and B-cell receptor (BCR) pathway inhibitors such as idelalisib and ibrutinib are currently established therapies for CLL. Although effective, these drugs frequently lead to resistance, but the mechanisms are still not fully understood. Activation-induced cytidine deaminase (AID) is a B-cell enzyme essential for antibody diversification. However, it can also introduce off-target mutations, leading to genomic instability. This study investigates whether treatment with BCR pathway inhibitors increases AID activity in CLL and whether this activity contributes to the development of drug resistance. Peripheral blood samples from CLL patients were collected before and after treatment with idelalisib or ibrutinib. Targeted sequencing was used to identify mutations in known AID off-target genes. Concurrently, AID-wild type (AID-WT) and AID-knockout (AID-KO) CLL cell lines were established and subsequently exposed to escalating doses of BCR pathway inhibitors to develop drug-resistant models. In patient samples, treatment with BCR pathway inhibitors was associated with an increase in AID-dependent mutations in off-target genes, including BCL2, MYC, and IRF8. The in vitro models efficiently recapitulated the patients’ data, as only AID-WT CLL cells accumulated mutations in the same AID off-target genes after drug exposure. However, no mutations were detected in genes that could mediate drug resistance. We conclude that BCR pathway inhibitors enhance AID mutational activity in CLL, but this does not appear to be directly involved in driving drug resistance. AID-targeted loci may nonetheless serve as biomarkers for monitoring genomic instability during treatment and inform further study. Full article

Mobile games have become one of the fastest-growing segments of the digital economy, and in-app advertisements represent a major source of revenue while shaping consumer attention and memory processes. This study examined the relationship between visual attention and brand recall of in-app advertisements in a mobile sports game using mobile eye-tracking technology. A total of 79 participants (47 male, 32 female; Mage = 25.8) actively played a mobile sports game for ten minutes while their eye movements were recorded with Tobii Pro Glasses 2. Areas of interest (AOIs) were defined for embedded advertisements, and fixation-related measures were analyzed. Brand recall was assessed through unaided, verbal-aided, and visual-aided measures, followed by demographic comparisons based on gender, mobile sports game experience and interest in tennis. Results from Generalized Linear Mixed Models (GLMMs) revealed that brand placement was the strongest predictor of recall (p < 0.001), overriding raw fixation duration. Specifically, brands integrated into task-relevant zones (e.g., the central net area) achieved significantly higher recall odds compared to peripheral ads, regardless of marginal variations in dwell time. While eye movement metrics varied by gender and interest, the multivariate model confirmed that in active gameplay, task-integration drives memory encoding more effectively than passive visual salience. These findings suggest that active gameplay imposes unique cognitive demands, altering how attention and memory interact. The study contributes both theoretically by extending advertising research into ecologically valid gaming contexts and practically by informing strategies for optimizing mobile in-app advertising. Full article

Systematically assessing the supply–demand disparities of urban–rural ecosystem services (ES) is a key pathway to optimizing resource allocation, promoting urban–rural integration and advancing regional sustainable development. Taking Zhengzhou City as a case study, this research evaluates and compares urban–rural differences across four dimensions: potential supply, actual supply, real human needs (RHN), and effective supply. Furthermore, focusing on actual supply, the study integrates a geographical detector and Bayesian belief network to identify key driving factors, delineate optimal optimization zones, and propose differentiated management strategies. The results show that: (1) Urban RHN accounts for 69.70% of the total in Zhengzhou, with a spatial pattern of “higher in the east and core, lower in the west and periphery”, and the internal heterogeneity is significantly greater than that of rural areas. (2) Potential supply is “higher in rural areas and in the west”, whereas actual supply is concentrated in central urban districts, reflecting a net service flow from rural to urban areas. (3) High-level effective supply areas cover 37.28% of urban regions, about 18 percentage points higher than rural regions. Rural deficits are primarily caused by low conversion efficiency of supply rather than insufficient potential. (4) Optimal urban optimization zones are mainly distributed in peripheral urban streets, while rural zones are concentrated in eastern townships. Through multidimensional supply–demand comparison and spatial optimization, this study provides a scientific basis for the coordinated enhancement of urban–rural ES, differentiated governance and regional sustainable development. Full article

Background: Chronic rhinosinusitis (CRS) affects nearly 9% of the global population with a rising incidence over recent decades. Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease pose significant global burden, and emerging evidence suggests pathophysiological links through shared bioenergetic dysfunction, peripheral-to-central inflammatory signaling, and altered nasal microbiota. This review evaluates the evidence for CRS as a potentially modifiable peripheral contributor to neurodegenerative disease progression. Methods: A systematic review was conducted using PubMed, Cochrane, Web of Science, Embase, and CENTRAL from January 2000 to July 2025. Search terms included “Chronic Rhinosinusitis,” “Neurodegeneration,” “Mild Cognitive Impairment,” “Alzheimer’s Disease,” “Parkinson’s Disease,” “Bioenergetics,” and “Microbiome.” Clinical and experimental studies exploring epidemiological links, mechanistic pathways, biomarkers, and therapeutic targets were included. Results: Twenty-one studies involving over 100,000 participants met the inclusion criteria. Existing meta-analytic evidence demonstrated significant associations between CRS and cognitive impairment, with patients scoring approximately 9% lower on global cognitive measures than controls. However, other large-scale cohort studies did not pinpoint an increased dementia incidence, suggesting CRS may contribute to early, potentially reversible cognitive decline without directly driving dementia onset. Neuroimaging studies revealed altered frontoparietal connectivity and orbitofrontal hyperactivity in CRS patients. Mechanistic studies support peripheral inflammatory cytokines disrupting the blood–brain barrier, autonomic dysfunction impairing mucociliary clearance, microbiome-driven amyloid cross-seeding, and compromised cerebrospinal fluid clearance via olfactory–cribriform pathways. Discussion: Evidence supports complex, bidirectional relationships between CRS and neurodegeneration characterized by convergent inflammatory, autonomic, and bioenergetic pathways. Therapeutic strategies targeting sinonasal inflammation, microbiome dysbiosis, and mitochondrial dysfunction represent promising intervention avenues. Recognizing CRS as a treatable factor in neurodegenerative risk stratification may enable earlier diagnosis and prevention strategies. Full article

Objectives: To investigate the profile of Th1- and Th2-type cytokines in response to Epstein–Barr virus (EBV) antigens and to correlate this immune signature with clinical relapses in Multiple Sclerosis (MS). Specifically, we aimed to evaluate the cellular and humoral immune response following stimulation with a pool of lytic and latent EBV proteins. Methods: We employed ELISpot and ELISA to quantify Interferon-gamma (IFN-γ), Interleukin-18 (IL-18), Interleukin-10 (IL-10), and the B-cell activation marker soluble CD23 (sCD23). Measurements were performed on peripheral blood mononuclear cells (PBMCs) from MS patients and controls following stimulation with EBV peptide antigens. Results: MS patients exhibited significantly higher levels of all tested cytokines compared to controls. A statistically significant positive correlation was noted between IL-10 and sCD23 levels (p < 0.03), with significant correlations also found between IL-10 and IFN-γ (r = −0.56) and between IFN-γ and IL-18 (p < 0.02), a finding that warrants cautious interpretation. Crucially, both IL-10 and sCD23 levels strongly correlated with the Expanded Disability Status Scale (EDSS) score (p = 0.0003 and p = 0.0001, respectively). Conclusions: Our findings suggest a chronic, dysregulated immune response to EBV antigens in MS patients, characterized by the co-activation of inflammatory Th1 pathways and robust B-cell activation. These results support a pathogenetic model where the EBV-specific immune response, perpetuated by infected B-cells, may directly contribute to the immunopathological processes driving central nervous system (CNS) damage and clinical relapses. Full article

Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood–brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes. Full article

Mountainous traditional villages represent unique socio-ecological systems that have evolved through centuries of adaptation to complex topographies and multi-hazard environments. Understanding their terrain–resilience coupling mechanisms is essential for risk-sensitive planning and heritage preservation in mountainous regions. This study integrates multi-source remote sensing data and GIS spatial analysis to investigate 57 national-level traditional villages in the southern Qinba Mountains, China. Using kernel density estimation (KDE), nearest neighbor index (NNI), and Geodetector modeling, we identify the spatial distribution characteristics and topographic driving forces that shape settlement patterns across macro-meso-micro scales. Results reveal that 83% of the villages are clustered in low-mountain and hilly zones (550–1200 m elevation), preferring slopes below 15° and south-facing aspects. Elevation exerts the strongest influence (q = 0.46), followed by slope (q = 0.32) and aspect (q = 0.29), forming a multi-level adaptation framework of “macro-elevation differentiation, meso-slope constraint, and micro-aspect optimization.” Morphological Spatial Pattern Analysis (MSPA) further indicates that traditional villages achieve ecological balance and disaster avoidance through adaptive spatial strategies such as terrace-based flood prevention, convex-bank stabilization, and platform-based hazard avoidance. These strategies are not merely topographic preferences but natural adaptation mechanisms formed by long-term responses to multi-hazard environments—dynamic adaptation processes that reduce disaster exposure and optimize resource use efficiency through active adjustment of site selection and spatial transformation (the disaster density in the 100m core zone buffer is 0.077 events/km², significantly lower than 0.290 events/km² in peripheral areas). These findings demonstrate that remote sensing techniques can effectively reveal the terrain–resilience coupling of traditional villages, providing quantitative evidence for integrating spatial resilience into cultural landscape conservation, ecological security assessment, and rural revitalization planning. The proposed multi-scale analytical framework offers a transferable approach for evaluating settlement adaptability and resilience in other mountainous cultural heritage regions worldwide. Full article

Sphingolipids are a large group of molecules, crucial components of all mammalian cells, that are particularly abundant in the central and peripheral nervous system and associated with important human brain functions. Sphingolipids are necessary for membrane organization and driving functions. Ceramide, sphingosine-1-phosphate and GM1, show bioactive properties. Ceramide and sphingosine-1-phosphate play a crucial role in the regulation of physio-pathological conditions. Small changes in their levels, in the ratio sphingosine-1-phosphate/ceramide as well as in chain length profiles of sphingolipids contribute to alter signaling pathways in neurons and glia, contributing to various neurological disorders. GM1 is considered a neurotrophic and neuroprotective compound and seems to be necessary for the correct functioning of neuronal membrane receptors, suggesting that a reduction in its level in the brain can be involved in neurodegenerative diseases. In this review, we give an overview of sphingolipid metabolism, summarizing the role of ceramide, sphingosine-1-phosphate, and GM1 in maintaining human health. Full article