Search Results (4,138)

Largemouth bass (Micropterus salmoides) is a major aquaculture species in China. Facility-based aquaculture, such as the “168” model, a high-efficiency recirculating system using funnel-shaped ponds, has promoted water conservation and improved aquaculture efficiency through structural innovation. However, fish die sporadically as the stocking density increases with increasing fish growth. To address this issue, three density groups were established, namely, low (2.5 ± 0.5 kg/m³), medium (4.0 ± 0.5 kg/m³), and high (7.5 ± 0.5 kg/m³). Histological examinations, biochemical assays, and transcriptomic and metabolomic analyses of liver tissues were performed, and fish health was comprehensively evaluated. Histopathological analysis revealed that progressive hepatic vacuolization and severe tissue damage occurred as the fish density increased. Biochemical indicators revealed that the immune system and growth underwent compensatory activation at medium density, shifting to immune suppression, growth impairment, and hepatic exhaustion at high density. Integrated omics analysis revealed that under medium-density stress, the urea cycle was impaired; under high-density stress, Ser metabolism in the liver was rerouted, potentially to overcome methyl donor depletion and prevent disorders of polyamine metabolism, accompanied by a gradual transition from compensatory activation to functional exhaustion. These findings improve our understanding of the physiological response mechanisms of fish to high-density stress. This study provides a theoretical basis for optimizing high-density aquaculture technologies such as the “168” model. Full article

Interpretability is essential for deploying deep learning (DL) models in electroencephalography (EEG)-based neurotechnology, particularly in brain–computer interfaces and clinical decision-support settings. Existing post hoc explainable artificial intelligence (XAI) methods often yield single-domain attribution maps, limiting their capacity to characterize the joint spatial, temporal, and spectral structure of EEG dynamics. In addition, perturbation-based strategies may disrupt physiological signal organization, whereas gradient-based methods require access to model internals and are therefore tied to specific classifier architectures. Here, we introduce space–time–frequency KernelSHAP (STF-KernelSHAP), a model-agnostic Shapley framework for physiologically coherent EEG explainability. The method comprises three stages. First, EEG trials are decomposed into structured channel–time–frequency cells using segment-wise spectral analysis. Second, coalitions are formed over complete channel–time–frequency cells and reconstructed in the signal domain to support physiologically informed perturbations. Third, class-conditional relevance is estimated with a KernelSHAP-based weighted surrogate model that uses only model outputs, enabling architecture-independent Shapley estimation. We evaluate STF-KernelSHAP on two prerecorded public datasets: the GIGA motor imagery/movement execution (MI-ME) dataset for motor imagery (MI) decoding and the IEEE DataPort EEG Data for Attention-Deficit/Hyperactivity Disorder (ADHD)/Control Children dataset for ADHD detection. For ADHD detection, the T-GARNet base classifier interpreted with STF-KernelSHAP achieved 73.33% accuracy and 79.86% area under the curve (AUC); these values characterize classifier performance rather than the explainer itself. We compare the framework against KernelSHAP, local interpretable model-agnostic explanations (LIME), Occlusion, Integrated Gradients, and gradient-weighted class activation mapping++ (Grad-CAM++). Fidelity is assessed with Deletion and remove and debias (ROAD), while qualitative analyses examine topographic and frequency-band attribution maps. Results show that STF-KernelSHAP remains functionally competitive with established XAI methods while providing window-dependent and frequency-specific explanations. Overall, STF-KernelSHAP offers a physiologically informed and model-agnostic alternative for multidomain EEG interpretability. Full article

Major depressive disorder (MDD) is not reducible to a single neurotransmitter deficit. Current explanations commonly involve monoaminergic dysfunction, hypothalamic–pituitary–adrenal axis dysregulation, immune-inflammatory activation, impaired neuroplasticity and synaptic dysfunction, together with metabolic and neurovascular abnormalities. Lipidomic studies have repeatedly identified glycerophospholipid abnormalities in MDD, but their mechanistic meaning remains unresolved because changes in bulk lipid abundance do not explain how altered lipid metabolism becomes a receptor-level neural signal. This review develops a testable interpretation of the lysophosphatidylcholine (LPC)–autotaxin (ATX)–lysophosphatidic acid (LPA)–LPA receptor (LPAR) axis in which LPC species generated during phospholipid turnover provide ATX substrates, ATX activity determines local LPA generation, LPA production and inactivation shape ligand availability, and LPAR signaling links the lipid product to neural output. This structure shifts the focus from total lipid abundance to matched assessment of lipid species, enzyme activity, anatomical site and receptor subtype. Human studies report lower serum and cerebrospinal fluid (CSF) ATX in MDD, lower CSF LPA 22:6 in MDD and schizophrenia, and negative total LPA findings that caution against biomarker oversimplification. Depression-relevant and broader stress- or anxiety-related experimental studies show that ATX, LPA and LPAR perturbation can affect hippocampal function, synaptic physiology, emotional behavior and stress resilience. The key unresolved issue is whether brain-accessible LPC species, active ATX, locally generated LPA, LPA inactivation capacity and receptor-specific output can be demonstrated within the same MDD-relevant fluid, brain-interface site or neural circuit. Future work should therefore move from fluid-level association toward pathway closure through targeted and spatial lipidomics, anatomical ATX activity mapping, LPA inactivation assays, blood–brain barrier (BBB)/interface analysis, LPAR perturbation and matched circuit or behavioral readouts. Full article

The autism spectrum disorder-associated SCN2A, ANK2, and SHANK-family genes encode molecularly distinct proteins that converge functionally on dendritic integration. Recent work established that ankyrin-B, encoded by ANK2, acts as an obligate dendritic scaffold for NaV1.2, encoded by SCN2A, in neocortical pyramidal neurons. Loss of this module mislocalizes dendritic NaV1.2, reduces dendritic Na⁺ influx, weakens backpropagating action potentials, and impairs synaptic maturation and long-term potentiation. SHANK proteins organize a complementary postsynaptic receptor scaffold within dendritic spines, coupling N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and metabotropic glutamate receptor (e.g., mGluR5) signaling to the actin cytoskeleton through layered PSD-95/GKAP/Homer interactions. Disruption of this scaffold can destabilize excitatory transmission, spine morphology, and plasticity. We propose that these dendritic shaft and spine-associated modules jointly regulate dendritic input–output gain and that their disruption may contribute to autism spectrum disorder by destabilizing, rather than uniformly shifting, excitatory integration across cortico-subcortical circuits relevant to sensory reactivity, behavioral flexibility, and social-valence processing. Here, we review the cortical evidence for this layered dendritic convergence and evaluate its potential relevance beyond the cortex. We assess the striatum, thalamus, and amygdala as subcortical sites where related dendritic scaffolding mechanisms may operate. The striatum provides the strongest current test case, with established roles for both NaV1.2 and SHANK3 in medium spiny neuron physiology and corticostriatal connectivity. Thalamic and amygdalar extensions are supported mainly by SHANK-related circuit and channelopathy data but lack direct evidence for ANK2–SCN2A involvement. The framework is experimentally testable: conditional Ank2 deletion in striatal, thalamic, and amygdalar cell types; dendritic Na⁺/Ca²⁺ imaging across Scn2a, Ank2, and Shank3 models; adult rescue experiments; and genetic-interaction designs would determine whether ankyrin-B supports dendritic excitability beyond the cortex and whether these genes converge on, rather than merely parallel, dendritic input–output gain. Validation in human subcortical tissue would then establish whether this dendritic scaffolding logic represents a shared point of convergence through which genetically distinct autism spectrum disorder-risk variants alter circuit function. Full article

Background/Objectives: Intra-articular injections are used for temporomandibular disorders (TMDs) resistant to conservative treatment. However, many reviews assess injectable agents combined with arthrocentesis or other co-interventions, limiting interpretation of their standalone effects. This overview aimed to summarize meta-analytic evidence on standalone intra-articular injections for temporomandibular joint disorders. Methods: MEDLINE, BASE, and Europe PMC were searched on 29 March 2026. Systematic reviews with quantitative meta-analyses evaluating standalone intra-articular TMJ injections were included. Data regarding injectable substances, clinical indications, and outcome domains were extracted and synthesized descriptively. Results: Three systematic reviews with meta-analyses were included. The evidence addressed platelet-rich plasma, corticosteroids, sodium hyaluronate, and physiological saline. Reported indications included degenerative joint disease, osteoarthritis, internal derangement, and arthritis. All included agents were reported to be associated with pain reduction. Conclusions: Meta-analytic evidence on standalone intra-articular injections for TMDs remains limited and heterogeneous. Available data suggest potential benefits, mainly for pain reduction, but do not establish clear superiority of any agent. The potential therapeutic activity of physiological saline should be considered when designing future injection trials. Full article

Glycosphingolipids (GSLs) are glycoconjugates in which a short and heterogeneous saccharide chain is attached to a lipid moiety called ceramide. Based on their sugar backbone, mammalian GSLs are primarily grouped into the ganglio-, lacto-/neolacto-, and globo-series. Sialic acid—containing GSLs are known as gangliosides. Complex ganglio-series gangliosides are particularly abundant in the brain, whereas simple ganglio-series gangliosides, as well as those belonging to other series or neutral GSLs, are less abundant and typical of non-neural tissues. Congenital disorders in the biosynthesis of the lipid moiety of sphingolipids (SLs) result from defects in enzymes and proteins involved in ceramide biosynthesis and transport. Congenital disorders in the biosynthesis of the sugar chain of GSLs specifically affect ganglio-series ganglioside biosynthesis and are caused by pathogenic variants in GM3 synthase (ST3GAL5) or GM2/GD2/asialo-GM2 synthase (B4GALNT1). Defective variants of the sialyltransferase ST3GAL3 and the galactosyltransferase B4GALT5 have been reported and proposed to impair GSL biosynthesis. The occurrence of these syndromes has provided new insights into the physiological and pathological roles of GSLs. Most of these disorders are associated with completely inactive enzyme variants, leading to severe neurological syndromes. Only a few cases highlighted variants that retained partial activity, resulting in milder phenotypes, which included non-syndromic intellectual disability. It is therefore conceivable that many undiagnosed patients, with mild neurological symptoms, may carry variants retaining residual enzyme activity, insufficient to ensure normal levels of brain GSLs. The purpose of this article is to encourage clinicians to look for additional GLS hereditary disorders associated with a milder phenotype. We also hope to boost future investigations by highlighting the most critical issues emerging from recent literature on SL and GSL biosynthesis and their related defects. Full article

Childhood trauma is adversely linked to a spectrum of physical and neurobehavioral disorders, further facilitating the intergenerational transmission of familial trauma. This review systematically elaborates on the profound impacts of childhood trauma on both survivors and their descendants. It provides an in-depth analysis of the complex mechanisms underlying this intergenerational transmission, and innovatively proposes an Environmental-Psychological-Physiological-Molecular (EPPM) multilevel cross-generational interaction model. This model encompasses behavioral transmission of negative parenting, neural encoding of traumatic stress, intergenerational neurophysiological basis, biological permeation of the intrauterine environment, and mechanisms of epigenetic remodeling. This provides a scientific basis for deepening our understanding of the long-term consequences of trauma, promoting the development of early intervention strategies from an interdisciplinary perspective, and breaking the intergenerational cycle of trauma. Full article

Sulfur-containing amino acids (SCAA) and their metabolites constitute an integrated metabolic network essential for central nervous system (CNS) function. In mammals, sulfur metabolism links one-carbon metabolism, the methionine cycle and the transsulfuration pathway, thereby connecting nutrient availability with redox regulation, methylation reactions, neurotransmitter synthesis and cellular adaptation to stress. Among these metabolites, methionine, cysteine, glutathione, taurine, homocysteine and hydrogen sulfide play key roles in neuronal physiology, mitochondrial homeostasis, synaptic plasticity and antioxidant defense. Alterations in SCAA metabolism have been increasingly associated with neurological and neurodevelopment disorders, which share common features such as oxidative stress, mitochondrial dysfunction, altered glutamatergic signaling, impaired methylation capacity and neuroinflammation. These pathological mechanisms are also observed following exposure to toxic metals, suggesting the existence of convergent pathways between environmental neurotoxicity and neurological diseases. Several studies showed that chronic exposure to arsenic, mercury, cadmium, lead, and other toxic metals disrupts sulfur amino acid homeostasis by affecting methionine remethylation, transsulfuration activity, glutathione synthesis and reactive sulfur species production. Due to sulfur-containing metabolites possessing antioxidant and metal-binding properties, these pathways are also involved in adaptive detoxification response. However, sustained disruption of sulfur metabolism may compromise neuronal resilience and increase vulnerability to neurological dysfunction. This narrative review integrates current evidence on the physiological roles of SCAA in the CNS, and examines how toxic metals disrupt sulfur metabolic pathways. By combining findings from experimental studies, human data and exploratory transcriptomic analyses, we propose that disruption of SCAA homeostasis represents a mechanistic link between environmental metal exposure and increased vulnerability to neurological disease. Full article

Muscle wasting associated with gastric cancer represents a complex, multifactorial systems disorder involving inflammatory, anabolic, mechanosensory, calcium-regulatory, mitochondrial, and proteostatic disruption. This review synthesizes current evidence regarding the cellular and physiological mechanisms involved in skeletal muscle dysfunction in gastric cancer and provides a unifying framework centered on loss of signaling coherence. Specifically, it examines IL-6/STAT3 and NF-κB inflammatory signaling, the myostatin–activin–ACVR2B–SMAD pathway, PI3K/Akt/mTOR signaling, mechanotransduction, excitation–metabolism coupling, calcium homeostasis, mitochondrial function, and proteostasis. Although individual components of these pathways have been implicated in muscle wasting associated with chronic disease, current evidence suggests that they interact through positive feedback loops. Inflammation, anabolic resistance, impaired force-to-signal conversion, mitochondrial stress, altered intracellular calcium homeostasis, and disrupted protein quality control may reinforce one another, contributing to metabolic, structural, and transcriptional instability. Within this context, muscle wasting reflects not only loss of muscle mass or strength, but also loss of functional integrity resulting from disrupted integration of mechanical, metabolic, inflammatory, and anabolic signals. Given the systemic nature of these effects, this review proposes kinesitherapy as a potentially useful nonpharmacological adjunctive strategy that may modulate inflammation, restore responsiveness to mechanical stimuli, support calcium homeostasis and mitochondrial function, improve anabolic sensitivity, and maintain protein quality control. Overall, this review presents a systems-biology model of gastric cancer-associated muscle wasting and supports further investigation of exercise-based therapies for this condition. Full article

Background: Mitochondria are the primary organelles that regulate cellular bioenergetic metabolism and maintain homeostasis, providing essential structural support for optimal cell survival. Nonetheless, advancing age leads to cumulative damage to mitochondrial structure and functional integrity, which is a defining characteristic of biological aging and is closely linked to the emergence and progression of numerous age-related diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic disorders. Scope of review: This article offers a thorough summary and review of mitochondrial quality control (MQC), emphasizing numerous critical processes, including mitochondrial biosynthesis, dynamic remodeling (fusion and fission), and mitophagy. We thoroughly elucidate the molecular pathways that regulate MQC and demonstrate how age-related dysregulation precipitates cellular senescence, highlighting the transition from physiological maintenance to pathological malfunction, which ultimately culminates in cellular aging. Conclusions and implications: This study systematically elaborates the pathophysiological mechanisms in the field, comprehensively evaluates the clinical translational potential of targeting the MQC pathway, highlights the key objectives of “restoring mitochondrial plasticity and removing dysfunctional mitochondria”, and explores novel intervention strategies. The restoration of normal mitochondrial function in cells throughout aging is a very promising path for precision medicine therapeutics with great translational potential, according to recent state-of-the-art research. The development of novel therapeutic approaches to improve functional healthy mitochondria can effectively delay aging and reduce the rising global burden of age-related diseases. Full article

Drosophila melanogaster, widely known as the fruit fly, has emerged as a pivotal model organism for studying development and signaling transduction. Its fully sequenced genome, short generation time, and powerful genetic toolkit—including the Gal4/UAS system, RNA interference, and CRISPR-Cas9—enable precise, tissue-specific manipulation and high-throughput functional analyses. Despite differences in anatomy, the internal organ systems of Drosophila melanogaster, including the nervous system, heart, fat body, oenocytes, and nephrocytes, exhibit conserved molecular pathways and physiological functions comparable to those of humans. The morphological differences between invertebrates and vertebrates have long led researchers to undervalue the studies of insects in underlying the pathogenesis of human diseases. Over the past decades, the fruit fly has been widely validated for modeling the pathogenesis of neurodegenerative, cardiovascular, metabolic, renal, and muscular disorders. In this review, we systematically summarize the conserved molecular pathways and organ functions between the fruit fly and human, and provide examples of recent studies that use the fruit fly as a model system to answer questions associated with human diseases. We also discuss how Drosophila help researchers to fulfill the gap from mechanistic study toward translational research, and provide methodological considerations regarding the utility of Drosophila models in drug screening. Full article

Background. Developmental dyslexia (DD) is a neurodevelopmental disorder characterized by persistent difficulties acquiring fluent reading. A core feature is impaired phonological processing, though its etiology remains debated. Two competing accounts attribute phonological deficits either to reduced acoustic sensitivity to lexical stress cues or to insufficient cognitive support during phoneme processing. Methods. To test these accounts, 57 Italian children (28 with DD, 29 typically developing) completed a phoneme monitoring task in which targets appeared in strong or weak syllables, varying in acoustic salience. A composite acoustic salience factor was derived from target cue properties, and an individual cognitive factor was computed from IQ, working memory, and shifting attention. Pupillometry was used to assess auditory sensitivity to acoustic salience and cognitive effort in real time. Results. The results showed that, behaviourally, children with DD showed significantly lower target identification accuracy and d’-sensitivity. However, pupil dilation during target processing did not differ between the two groups, while children with DD showed reduced pupillary responses on trials involving distractor rejection and missed targets. These physiological patterns correlated primarily with individual cognitive scores rather than acoustic salience. Conclusions. Taken together, these findings point toward an important role of individually varying cognitive resources during phonological processing and highlight the value of pupillometry as a sensitive, real-time index of cognitive engagement during a phonological task. Full article

Introduction: Vascular aging is characterized by endothelial dysfunction, impaired vasomotor regulation, and structural remodeling. Iron overload may accelerate these processes through oxidative stress, but its effects on cardiovascular regulation remain incompletely understood. Methods: We investigated cardiovascular dynamics in patients with hereditary hemochromatosis using wavelet-based time–frequency analysis of electrocardiographic and blood pressure signals. Continuous beat-to-beat recordings were analyzed to assess oscillatory patterns and phase coherence across physiologically relevant frequency bands. Results: Patients with iron overload exhibited significant alterations compared with healthy controls, including reduced cardiac-related variability, increased peripheral blood pressure oscillations, and disrupted phase coherence between cardiac and vascular signals. These findings indicate impaired integration between central cardiac activity and peripheral vascular regulation. Conclusions: Iron overload is associated with early cardiovascular dysregulation, likely driven by autonomic imbalance and vascular dysfunction. Wavelet-based metrics may enable sensitive detection of subclinical alterations and improve early risk stratification in patients with iron metabolism disorders. Full article

Brain-derived neurotrophic factor (BDNF) is one of the most pleiotropic signaling molecules in mammalian biology, regulating processes ranging from neuronal survival and synaptic plasticity to metabolic homeostasis. Under physiological conditions, BDNF expression is tightly regulated; however, it may be disrupted by a variety of adverse factors, including chronic psychological stress, sleep deprivation, oxidative stress, inflammation, aging, and metabolic imbalance. Prolonged exposure to any of these factors can chronically reduce BDNF levels, contributing to numerous disorders whose systemic consequences remain difficult to define conclusively. This uncertainty arises because the available evidence is drawn from heterogeneous sources including many species, wild-type and various gene-knockout models, and pharmacological studies of differing specificity—yielding findings that are often inconsistent and difficult to compare. Consequently, the full spectrum of multisystemic effects resulting from long-term partial BDNF deficiency remains incompletely characterized. The SD-BDNFtm1sage rat line, developed by SAGE/Envigo/Inotiv using zinc finger nuclease technology, was created to fill this gap. Sprague–Dawley rats with a heterozygous genotype retain one functional allele of the Bdnf gene, resulting in a partial, permanent reduction in BDNF expression that persists throughout life. This chronic and moderate BDNF deficiency allows the animal to survive but is insufficient to maintain normal homeostasis, disrupting many physiological systems and behavioral responses. This review summarizes findings from studies using the SD-BDNFtm1sage rat line and shows that its phenotypic spectrum—susceptibility to mental disorders, sleep disturbances, metabolic abnormalities, altered nociception, and impaired neuromuscular adaptation—closely reflects the multisystemic consequences of chronic BDNF deficiency. This broad relevance makes the model particularly useful for research with potential medical applications. Full article

Fascia is increasingly recognized as a dynamic functional system. It can actively sense, transmit, and regulate mechanical, sensory, and metabolic signals. Why does fascia play such a critical role in chronic pain and movement disorders? Researchers are now rethinking the pathophysiological mechanisms underlying this role. Previous systematic reviews have typically focused primarily on specific mechanisms or interventions. In contrast, this study takes a holistic view of fascial function. It integrates multiple physiological functions of the fascia: mechanical integration, sensory modulation, cellular and matrix remodeling, as well as metabolic and immune regulation. From the perspective of functional imbalance, we further explore the pathological mechanisms associated with the fascia. Building on this, we then focus on how to assess fascial function from multiple dimensions and on specific targeted interventions. For assessment, we have systematically compiled a set of multi-stage quantitative techniques. These include clinical palpation, ultrasound, and elastography, tissue mechanics testing, microdialysis, omics approaches, electrophysiological testing, and digital modeling. For interventions, we have listed a range of modulating approaches, such as manual therapy, exercise rehabilitation, dry needling and acupuncture, fascial injections, targeted drugs, and biotechnological materials derived from tissue engineering. This review summarizes a clinical decision-making framework guided by the assessment of fascial functional status. It emphasizes a systematic approach and links quantitative diagnosis with precise interventions. Additionally, it provides a literature synthesis for understanding fascial mechanisms and related disorders and offers a reference foundation for the field’s transition from empirical treatment to measurable, reproducible, and individualized practice. Full article