Search Results (590)

The Qingshankou Formation shales in the southeastern uplift of the Songliao Basin provide an ideal archive for constraining the controls of paleoenvironment on organic matter enrichment. Taking the shale succession at the Niaohexiang section of Binxian as the study object, we combined field sampling with TOC measurements, whole-rock X-ray diffraction, and major, trace, and rare earth element analyses. The strata are dominated by black shale and dark gray mudstone, with mineral assemblages composed mainly of clay, felsic, and carbonate minerals; argillaceous shale exceeds 60%. Normal alkanes display a post-peak distribution with C₂₇ as the dominant peak, low Pr/Ph ratios, and gammacerane index values of 0.18–0.26. Regular steranes are generally V-shaped, whereas some samples show high C₂₉ sterane contents and a reversed L-shaped pattern. Major elements are dominated by SiO₂ and Al₂O₃, trace elements such as Sr and Ba are relatively enriched, and rare earth elements show light REE enrichment with a pronounced negative Eu anomaly. These signatures indicate an upper-crustal felsic provenance and a continental island arc tectonic setting. Organic matter contents are low and derived mainly from terrestrial higher plants with minor aquatic input. Paleoenvironmental reconstruction suggests deposition in a freshwater to slightly brackish, semi-arid, anoxic-reducing shallow lacustrine setting with relatively low productivity, whereas dolostone formed under more saline, arid, and more productive conditions. Climatic fluctuations, salinity variations, and alternating redox states jointly controlled organic matter enrichment, and late-stage lacustrine salinization and anoxia associated with dolostone horizons enhanced organic matter preservation. Full article

Recent advancements in neuroproteomics have enabled detailed analysis of protein expression in the human brain, yet resolving synaptic dysfunction—a central feature of many neurological and psychiatric disorders—requires careful methodological consideration. Leveraging the high sensitivity of modern liquid chromatography-tandem mass spectrometry (LC-MS/MS), we evaluated the utility of whole-tissue lysates versus enriched synaptosome preparations for detecting synaptic protein signatures. First, we optimized and standardized a sample preparation protocol for frozen human gray matter (GM) by refining the suspension trapping (sTRAP) digestion method using thin human tissue sections. We accomplished low technical variation by minimizing sample handling and achieved a highly reproducible sample preparation workflow by rigorously applying standardization and randomization across dissection, processing, and LC-MS/MS runs. Second, comparative LC-MS/MS analysis showed that while whole-tissue lysates provide a high-throughput survey of the synaptic proteome, synaptosome isolation is required to investigate synapse-specific proteins to detect alterations at the terminal that are obscured in the soma. Because these methods offer distinct but synergistic levels of information, we recommend a tiered neuroproteomics strategy. This approach utilizes whole-tissue lysates for broad disease-associated screening and consistent quantification in large cohorts, followed by targeted synaptosome proteomics to provide a unique window of insight into synaptic composition and stability. This integrated workflow respects the biological necessity of spatial resolution while maintaining the reproducibility required for robust human brain proteomics. Furthermore, initial tissue-level analysis provides the necessary context to correctly interpret synaptosome data in cases of global synapse loss or gain. Full article

Background/Objectives: Non-sedate magnetic resonance imaging (MRI) can be challenging for young children with neuromotor disabilities, often resulting in motion-degraded images that complicate interpretation in the context of underlying neuropathology. This study aimed to characterize tolerance factors and barriers related to awake MRI of the pediatric brain and to examine additional considerations in analyzing structural scans affected by motion and pathology. Methods: 10 children (mean age 5y9m; 5 girls; GMFCS level IV) with cerebral palsy (CP) underwent non-sedate 3T MRI of the brain. Tolerance factors and challenges were documented. MRI quality and automated structural preprocessing with Freesurfer (FS) v.8.0 were reviewed by a pediatric neuroradiologist and neurologist. To assess the impact of motion, automated basal ganglia segmentation was compared with manual segmentation. Segmentation accuracy was characterized using Dice Coefficient (D). Results: Five participants (50%) tolerated non-sedate structural MRI, although two of them were unable to remain still. Factors affecting MRI tolerance included sensitivity to scanner noise (n = 4), hyperkinetic movement (n = 2), difficulty with positioning/padding (n = 4), fear of clinical environment (n = 2) or confined scanner interior (n = 2), and earbud discomfort (n = 3). Automated structural preprocessing with FS yielded discrepancies in gray-white matter boundaries in motion-degraded scans, necessitating manual correction. Automated segmentation of motion-compromised scans closely agreed with manual delineation of the caudate (D ≥ 0.85) and putamen (D ≥ 0.78), while the pallidum was least reproducible (D = 0.58). Conclusions: Tailored acquisition and processing strategies are necessary to support non-sedate MRI in children with CP, preserve downstream neuroimaging analyses, and promote inclusion of underrepresented populations in research. Full article

Spinal cord injury (SCI) triggers a secondary injury cascade characterized by persistent innate immune activation, chronic neuroinflammation, and progressive tissue loss that limits functional recovery. Here, we evaluated a systemic combination treatment using propentofylline (PPF), a glial modulator, together with interleukin-4 (IL-4), a cytokine associated with repair-related myeloid responses. In vitro, PPF enhanced IL-4-dependent induction of arginase-1 (ARG1) in TNFα-primed BV2 microglia. In vivo, adult Fischer rats of both sexes received vehicle, PPF, IL-4, or combined PPF + IL-4 beginning within 1 h after moderate T8 contusive SCI and continuing daily for 14 days. Locomotor recovery was assessed longitudinally for 8 weeks, followed by histological and immunohistochemical analyses. Combined PPF + IL-4 treatment produced the greatest improvement in gross and skilled locomotor recovery compared with vehicle, or either monotherapy. At 8 weeks post-SCI, the combined therapy aligned with a reduction in chronic lesion-associated p-p38 MAPK, decreased pP65 NFkB (RelA) activation, increased expression of reparative factors ARG1 and CD206, as well as reduced lesion cavitation and trends toward greater gray and white matter preservation. Stratification of functional data by sex showed BBB improvements with combined PPF + IL-4 in both males and females after SCI. Together, these findings show that combined systemic PPF and IL-4 treatment was associated with improved functional recovery, reduced lesion cavitation, and changes in lesion-associated molecular and histological endpoints after SCI, supporting further preclinical investigation. Full article

With the increasing prevalence of neurodegenerative diseases driven by population aging, imaging-based biomarkers are needed to quantify brain aging at an early stage. Brain age, which estimates structural brain aging relative to chronological age, has emerged as a useful indicator. Prior work has mainly used T1-weighted MRI with deep learning models such as convolutional neural networks (CNNs) or transformers; however, many approaches insufficiently capture three-dimensional structural continuity and localized anatomical patterns, and tissue-specific aging in gray matter (GM) and white matter (WM) is often treated as auxiliary. To address these limitations, we propose a 3D Global–Patch Transformer framework for brain age prediction that directly processes volumetric data while jointly learning global brain structure and local anatomical features. Our model runs global and patch pathways in parallel and explicitly incorporates GM and WM structural maps alongside T1-weighted MRI to encode tissue-specific aging signals. Experiments on multiple public datasets, including IXI and OASIS, show that the proposed method reduces mean absolute error (MAE) by approximately 10–15% compared with CNN-based and single-input transformer baselines, with notably improved performance in older populations, highlighting the value of tissue-level structural information for brain age estimation. Full article

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of gait disturbance and cognitive impairment in older adults, yet its diagnosis remains challenging and controversial. The core difficulty lies in distinguishing true hydrocephalus from ventricular enlargement secondary to cerebral atrophy or neurodegenerative disease, a distinction now recognized as non-binary. In many patients, ventricular enlargement reflects a continuum ranging from predominantly hydrocephalic iNPH to mixed pathological states combining impaired cerebrospinal fluid (CSF) dynamics and neurodegeneration. Conventional neuroradiological markers, including the Evans Index, the callosal angle, and the disproportionately enlarged subarachnoid-space hydrocephalus (DESH) pattern, provide useful qualitative guidance but are limited by their two-dimensional nature, interobserver variability, and poor sensitivity for differential diagnosis and outcome prediction. Over the past decade, advances in artificial intelligence-based brain volumetry (AI-BrV) have introduced a new paradigm for quantitative structural assessment. By enabling automated, anatomically precise, and reproducible three-dimensional quantification of ventricular and extraventricular CSF, cortical and subcortical gray matter, deep gray matter nuclei, and periventricular white matter, AI-BrV addresses many limitations of traditional imaging approaches. Beyond absolute volume measurements, AI-BrV enables the derivation of composite indices and ratios that may capture disease-specific structural phenotypes and better reflect the underlying pathophysiology of ventricular enlargement. Importantly, AI-BrV pipelines can be applied retrospectively to large legacy neuroimaging datasets and compared with extensive publicly available repositories, facilitating normative modeling, cross-disease analyses, and external validation of volumetric biomarkers. When integrated with clinical data and multivariable statistical or machine-learning frameworks, these approaches hold promise for improving patient selection, refining disease categorization, and supporting more rational decision-making regarding CSF diversion. In this context, AI-BrV offers a unifying framework for reconciling divergent clinical perspectives and advancing iNPH toward a more precise, reproducible, and evidence-based diagnostic and therapeutic paradigm. Full article

This study examines the marble resources of the Mani peninsula, southern Greece, a region that has long been known for its white, gray-black (bigio antico), green (cipollino verde Tenario), and particularly red (rosso antico or lapis Taenarium) and dark (nero antico) marbles. Based on extensive fieldwork, more than 90 quarrying sites were documented, several of which were recorded for the first time. This study provides a systematic characterization of these stones through combined mineralogical, petrographic, and stable isotopic (δ¹⁸O, δ¹³C) analyses of 27 representative samples. The results confirm the presence of calcitic marbles, which vary in color due to hematite in the red varieties, graphite and organic matter in the gray-black and black types, and chlorite in the green marbles. The isotopic results demonstrate a generally high degree of homogeneity, although the red marbles display greater variability, complicating their distinction from analogous stones in Asia Minor, such as those from Iasos and Milas. Quarrying of Mani marbles began in the Bronze Age and reached its peak during Roman times. It continued into the Byzantine period, with renewed exploitation in the 19th and 20th centuries. This study highlights the significant role of Mani in the ancient marble trade and contributes to ongoing debates about the provenance of famous red, white, and black marbles across the Mediterranean. Furthermore, it establishes a strong reference framework, integrating new analytical results with the existing literature, providing an updated mineralogical, petrographic, and isotopic database for provenance studies of marble artifacts. Full article

Objectives: We aimed to compare performance-based functional ability and cognitive screening performance to determine the cortical thickness relationship in cognitively unimpaired (CN) elders, mild cognitive impairment (MCI) and dementia patients, as well as to compare performance-based and proxy-evaluated functional ability and to determine its cerebral white and gray matter correlates. Methods: In total, 22 CN, 32 MCI, and 21 dementia patients were included in this study. They underwent clinical, cognitive, and Magnetic Resonance Imaging (MRI) assessment. Individuals were evaluated with the Mini-Mental State Examination (MMSE), the Rey Auditory Verbal Learning test (RAVLT), the Activities of Daily Living Questionnaire (ADL-Q) and the Direct Assessment of Functional Status-Revised (DAFS-R). Results: Higher ADL-Q scores were significantly associated with lower cortical thickness (bilateral temporoparietal regions, including the inferior temporal lobes and precuneus), p < 0.05. The DAFS-R scale showed a relationship with greater cortical thickness across extensive regions of the bilateral frontal, parietal, and temporal cortices (p < 0.05). MMSE presented a more focal association, primarily in canonical memory-related areas, including the medial and lateral temporal lobes and inferior parietal regions (p < 0.05). Conclusions: Functional independence measured by ADL-Q was associated with frontal and parietal cortical thickness, while DAFS-R scores demonstrated a more diffuse evaluation of cortical atrophy. Additionally, performance-based functional abilities according to the DAFS-R appear to be a stronger marker of cortical thickness than ADL-Q and MMSE. Full article

Huntington’s disease (HD) is characterized by progressive striatal atrophy and complex proteomic changes in the central nervous system. Using the ultrasensitive Next-Gen Ultra-Sensitive Immunoassay (NULISA) proteomic platform, we analyzed cerebrospinal fluid (CSF) from 88 persons with HD to dissect the biological correlates of gray matter loss. Our findings reveal a distinct “Two-Track” model of pathology. The first track, marked by the axonal damage protein neurofilament light chain (NEFL), showed a strong inverse correlation with putamen volume (Pearson r = −0.53, p < 0.001), reinforcing its utility as a proxy for structural neurodegeneration. The second track was defined by a positive association between the immune regulator TNFRSF8 (CD30) and putamen volume (Pearson r = 0.36, p < 0.001), reflecting a decline in active immune-regulatory signaling as striatal atrophy advances. Given its established role in immune modulation, TNFRSF8 was pre-specified for follow-up to further interrogate this neuro-immune axis. Crucially, TNFRSF8 maintained an independent association with striatal volume (Beta = 0.24, p = 0.008) even after controlling for NEFL, genetic burden (CAG-Age Product score), and sex. Supplementary analyses confirmed that this structural–immune axis is localized specifically to the striatum—showing no association with generic structural control regions—and is driven by CAG repeat length rather than chronological aging. Furthermore, bidirectional mediation analysis supported an atrophy-driven model, where striatal volume statistically mediates the relationship between genetic burden and downstream immune dysregulation (p = 0.010). These results demonstrate that maladaptive immune signaling is a distinct pathological correlate in HD, separable from general cytoskeletal damage. This dual-axis framework warrants evaluation in larger longitudinal and interventional studies to guide future biomarker-driven patient stratification and target engagement. Full article

Background: Sleep is a complex physiological process, crucial for cognitive functioning, emotional regulation, and overall health. Recent advances in genomics and neuroimaging have illuminated the intricate relationship between genetics, sleep architecture, and brain changes. This study investigated the association between sleep duration genetics, through a Sleep Duration Polygenic Index (Sleep PGI), and brain changes (total cortical thickness, white matter volume, gray matter volume, white matter hyperintensities volume) in cognitively healthy adults aged 20–80 years old. Methods: Using longitudinal data from the Reference Ability Neural Network (RANN) and Cognitive Reserve (CR) studies, we examined the impact of Sleep PGI on brain measures (total cortical thickness, gray matter volume, white matter volume, WMH volume) over time. Generalized Estimated Equations were used for the statistical analysis. Analysis was performed in the total sample (n = 94) and in three age-groups (young, middle, old). Results: Across age, higher Sleep PGI was associated with higher temporal WMH volumes over time. In models considering an interaction of age between Sleep PGI and time in study, age emerged as a significant moderator for outcomes of hippocampal volume, cortical white matter volume, and WMH volume (total, parietal) as outcomes. Conclusions: Sleep duration polygenic score was associated with changes in the brain in cognitively healthy adults. Genetic predisposition for longer sleep duration was associated with more favorable longitudinal trajectories against brain decline, a result mostly driven by younger adults. These findings underscore the importance of maintaining optimal sleep duration and the potential for personalized interventions to improve sleep and brain health. Full article

Severe mental illnesses, including schizophrenia and schizophrenia-like disorders, have been associated with premature neuronal and glial senescence, microglial activation, and gray matter volume reduction. These changes may drive clinical symptoms of schizophrenia, including cognitive impairment. Aryl hydrocarbon receptor, abundantly expressed in the intestinal and blood–brain barrier, is the master regulator of both tight junctions and cellular senescence. Under pathological circumstances, this receptor may promote premature gut aging, enabling the translocation of bacteria or their components from the gastrointestinal tract into systemic circulation and from there into the central nervous system. In this review article, we discuss a potential mechanism of schizophrenia–microorganismal migration, microglial activation, and gray matter volume reduction. We also focus on potential interventions for maintaining barrier function. These approaches include natural and synthetic modulators of the aryl hydrocarbon receptor as well as biophysical strategies to preserve barrier integrity and prevent central nervous system pathology. Full article

Parkinson’s disease (PD) is a heterogeneous clinical syndrome representing the final stage of a complex and long-lasting neurodegenerative process that involves not only dysfunction of the dopaminergic system but also impairments in other neurotransmitter systems. The diversity of the clinical presentation of PD, together with the existence of Parkinsonian syndromes and atypical Parkinsonism—such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB)—has important implications for rehabilitation outcomes and underscores the need for individualized, stage-dependent therapeutic approaches. Juggling is a complex motor activity that integrates cognitive, visuomotor, and balance processes, requiring a high level of concentration, precision, and motor adaptation. In recent years, there has been growing interest in this form of activity as a potential tool for supporting neuroplasticity, cognitive functions, and neurological rehabilitation. The aim of this review was to summarize current scientific evidence on the effects of juggling training on cognitive functions, visuomotor coordination, and balance, as well as to discuss the potential benefits of combining it with controlled hypoxia in patients with Parkinson’s disease (PD). This narrative review additionally considers how disease heterogeneity and stage of progression may influence the effectiveness of such multimodal interventions. This paper reviews the literature concerning the neurophysiological basis of learning to juggle and the mechanisms of brain plasticity, including increases in gray matter volume, improvements in white matter integrity, and reorganization of neuronal networks in motor and associative regions. Attention is drawn to the synergistic potential of combining juggling training with exposure to moderate, controlled hypoxia, which may induce an adaptive response involving the transcription factor HIF-1α, enhance the expression of brain-derived neurotrophic factor (BDNF), and promote angiogenesis and mitochondrial biogenesis. Although juggling and hypoxia are not directly related to training stimuli, both interventions activate overlapping and complementary neuroplastic pathways, providing a conceptual rationale for their parallel consideration and potential integration within future rehabilitation protocols. Juggling delivers task-specific motor–cognitive learning, whereas hypoxia may amplify molecular plasticity signaling, potentially enhancing responsiveness to motor interventions, particularly in patients at early stages of PD when compensatory mechanisms and neuroplastic capacity are relatively preserved. Findings from existing studies suggest that juggling under controlled hypoxic conditions may represent an innovative, safe, and multimodal form of training that supports both cognitive and motor components. Such effects may be particularly relevant in patients at early stages of PD, when compensatory mechanisms and neuroplastic potential are relatively preserved. Such an intervention may contribute to improvements in balance, attention, executive functions, and cognitive flexibility, which is particularly relevant in the context of rehabilitation for patients with neurodegenerative diseases. Importantly, to date, no randomized clinical trials have directly examined juggling performed under controlled hypoxic conditions in PD. Therefore, the present concept should be regarded as translational and exploratory, integrating evidence from juggling-induced neuroplasticity and hypoxia-related physiological adaptations. In this context, the proposed approach represents a proof-of-concept framework for future multimodal interventions rather than an established therapeutic strategy. Available evidence suggests that combining complex sensorimotor skill training with physiological modulation of the internal environment may constitute a novel direction in PD rehabilitation, extending beyond conventional exercise-based models. Despite promising reports, further well-designed clinical studies are needed to determine the optimal training parameters (frequency, intensity, duration, and degree of hypoxia), to evaluate the long-term sustainability of therapeutic effects, and to account for the heterogeneity of PD and related Parkinsonian disorders. Full article

As a typical ecologically degraded mining area, the Jiangcang Mine in Qinghai is characterized by severely depleted soil nutrients and reduced biodiversity, making scientifically grounded soil-amelioration measures urgently necessary to facilitate vegetation reconstruction and enhance soil ecological functions. To determine the optimal fertilization rate, we conducted a two-factor randomized block experiment over an approximately two-year period after plant sowing, using pelletized organic fertilizer and sheep manure as the primary amendments, with three replicates per treatment, and with application rates selected based on commonly used ranges in alpine grassland restoration and the availability of local organic resources in the mining area. Sheep-manure treatments were set at three levels at 0 (S0), 20 (S1), and 40 (S2) kg·m⁻², while pelletized organic fertilizer was applied at three rates at 0.0 (F0), 1.5 (F1), and 3.0 (F2) kg·m⁻². The combination of the two factors resulted in nine treatments: S0F0, S0F1, S0F2, S1F0, S1F1, S1F2, S2F0, S2F1, and S2F2. The results showed that fertilization significantly improved vegetation height, canopy cover, plant density, and aboveground biomass, with the strongest promotive effects observed under S2F2 and S2F1. Compared with other treatments, S2F2 markedly increased soil moisture content, pH, soil organic matter, available nitrogen, available phosphorus, as well as total nitrogen, 6.96-, 2.91-, 1.70-, 5.04-, 2.51-, and 3.91-fold relative to the control, respectively. The S0F2 treatment significantly enhanced bacterial Observed Richness, Shannon, and Chao1 indices, as well as simultaneously increasing fungal Observed Richness and Chao1 index. Vegetation height and density exhibited the strongest positive correlation under S2F1, whereas vegetation cover and aboveground biomass were most strongly correlated under S2F2. A gray relational analysis performed on 15 indicators ranked S2F0 as having the highest relational degree and comprehensive score, followed by S2F2 and S2F1. In summary, the combined application of approximately 40 kg·m⁻² of sheep manure without pelletized organic fertilizer showed the highest comprehensive restoration performance under the experimental conditions of this alpine mining area. Full article

Cognitive impairment (CI) is a common and disabling manifestation of multiple sclerosis (MS), yet it remains underdiagnosed in clinical settings. This study aims to identify the volumetric MRI markers of CI in MS patients. A total of 79 MS patients were enrolled; after exclusions, 63 with relapsing-remitting MS (RRMS) and 7 with primary progressive MS were analyzed. All participants underwent neuropsychological testing (CVLT, BVRT, CTT, VFT, VST, and SDMT). Brain volumes were analyzed using FreeSurfer. In RRMS, 59% had CI (35% single-domain, 24% multidomain). Multidomain CI was linked to reduced left cerebellar white matter and bilateral pallidum volumes, slight choroid plexus enlargement, and higher lesion volume versus cognitively preserved patients. Significant correlations were found between brain volumes and cognitive test scores: cerebellar and cerebral white matter, corpus callosum, subcortical gray matter, and thalamus volumes correlated positively with measures of processing speed, memory, and verbal fluency, while higher lesion load and larger choroid plexus volumes were associated with poorer cognitive performance. CI in MS is linked to both global and regional brain atrophy, as well as lesion load. Volumetric MRI, including choroid plexus analysis, may represent candidate imaging correlates of CI; however, longitudinal and externally validated studies are needed to confirm their predictive value and clinical utility. Full article

A 78-year-old woman with a history of rheumatoid arthritis (treated with methotrexate) developed disturbed consciousness, emesis, and intestinal perforation. Initial labs revealed hyperammonemia (189 μg/dL) and hypertonic dehydration. Despite ammonia normalization, her neurological status improved only slightly, necessitating additional tests. Cerebrospinal fluid analysis showed no pleocytosis but positive oligoclonal bands and markedly elevated myelin basic protein (>500 pg/mL). Serum autoimmune markers were negative, including anti-aquaporin-4 (AQP4), anti-myelin oligodendrocyte glycoprotein (MOG), and anti-glial fibrillary acidic protein (GFAP) antibodies. MRI revealed T2/DWI-hyperintense lesions in the left parietal lobe and cerebellum. Crucially, extensive T2/DWI-hyperintense lesions with diffusion restriction spanned the white matter from the medulla oblongata to the lumbar spinal cord. Axial spinal DWI demonstrated diffuse hyperintensity throughout the entire white matter, accompanied by gray matter atrophy. Subsequent metabolic screening revealed low folate and hypocupremia (34 μg/dL) as well as urinary orotic acid and low serum citrulline, suggesting late-onset ornithine transcarbamylase (OTC) deficiency. Given the clinical context, this was interpreted as a metabolic breakdown rather than an established genetic diagnosis. This case is characterized by a long, diffusion-restricted lesion from the brainstem to the spinal cord that does not correspond to vascular territories. She experienced sudden death. We hypothesize that an underlying metabolic disorder, nutritional deficiencies and drug-induced neurotoxicity contributed to lesion formation. Full article