Search Results (1,775)

Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. We determined the crystal structure of the Fyn KD-saracatinib complex at 2.22 Å resolution. The kinase adopts an active-like conformation with the DFG motif and αC-helix in the ‘in’ state and a conserved β3 αC Lys-Glu salt bridge. Saracatinib occupies the adenine and ribose pockets, and engages the hinge through direct and water-mediated hydrogen bonding while complementing a hydrophobic back pocket by van der Waals contacts. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues. Full article

The unique physicochemical properties of gold nanoparticles (GNPs) have made them versatile tools for biomedical applications, such as imaging, therapy, and drug delivery. The surface modification of GNPs with polymers or biomolecules can enhance their colloidal stability and facilitate internalization into cells. However, the efficient and biocompatible delivery to the central nervous system remains a major challenge, as many existing nanocarriers show poor capacity to cross the blood-brain barrier. We developed a method to coat GNPs with linear polyethyleneimine (GNP@PEI) through a chemical reduction bottom-up approach, in which linear PEI hydrochloride acts simultaneously as a reducing and stabilizing agent of colloidal dispersion. This strategy yielded monodisperse spherical GNP@PEI nanoparticles with an average diameter of 50 nm. The physicochemical profile, biocompatibility, and capacity for neural uptake of this potentially brain-targeted nanoplatform were then evaluated. GNP@PEI nanoparticles exhibited high biocompatibility in several primary neural cultures and cell lines, with cellular uptake showing clear cell-type-dependent differences. In vivo studies carried out in a murine model demonstrated that after the intranasal or intraperitoneal administrations of GNP@PEI nanoparticles, detectable levels of gold were found in several organs, including the brain. Collectively, these findings highlight the potential of GNP@PEI as a promising nanoplatform for brain-targeted delivery and for advancing the development of therapeutic strategies for neurological disorders. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, characterized by persistent inattention, hyperactivity, and impulsivity. This narrative review aims to synthesize and critically evaluate recent large-scale magnetic resonance imaging (MRI) studies to clarify the neuroanatomical and functional brain alterations associated with ADHD in children. By addressing current gaps in understanding, this work seeks to identify reliable neurobiological markers that could improve diagnostic accuracy and guide personalized interventions. The literature reveals that large-scale structural MRI studies consistently report abnormal development in total cortical volume and surface area, prefrontal cortex volume, and basal ganglia volume in children with ADHD. Moreover, gray matter alterations show significant age-dependent effects, with the degree of impairment potentially serving as neurobiological markers. Diffusion magnetic resonance imaging studies reveal disrupted white matter microstructures in regions such as the left uncinate fasciculus, superior and inferior longitudinal fasciculi, corpus callosum, cingulum, and internal capsule. Importantly, these white matter abnormalities often persist into adulthood, highlighting their clinical relevance. Functional MRI findings indicate reduced global connectivity within core hubs of the default mode network in children with ADHD. Furthermore, deficits in inhibitory control identified via fMRI may represent one of the neurofunctional signatures that differentiates ADHD from typically developing controls. By consolidating evidence from large-scale multimodal MRI studies, this review provides a comprehensive understanding of the neurodevelopmental alterations in ADHD and underscores their potential utility for improving diagnosis and treatment. Full article

This work investigates the feasibility of synthesis hybrid x Gd₂O₃ + (100 − x) Fe₃O₄ nanoparticles using the scalable method of high-energy ball milling for dual-contrast magnetic resonance imaging applications. Comprehensive studies of the structure, magnetic and functional properties of the hybrid nanoparticles were conducted. It was found that the milling process initiates the transformation of the cubic phase c-Gd₂O₃ ($\mathrm{I}\mathrm{a}\overline{3}$) into the monoclinic m-Gd₂O₃ (C2/m). Measurements of the magnetic properties showed that the specific saturation magnetization of the Fe₃O₄ phase is substantially reduced, which is a characteristic feature of nanoparticles due to phenomena such as surface spin disorder and spin-canting effects. The transmission electron microscopy results confirm the formation of hybrid Fe₃O₄-Gd₂O₃ nanostructures and the measured particle sizes show good correlation with the X-ray diffraction results. A comprehensive structure–property relationship study revealed that the obtained hybrid nanoparticles exhibit high r₂ values, reaching 160 mM⁻¹s⁻¹ and low r₁ values, a characteristic that is determined primarily by the presence of a large fraction of Gd₂O₃ particles with sizes of ≈30 nm and Fe₃O₄ crystallites of ≈10 nm. Full article

In today’s world, unhealthy living habits have contributed to the rise in metabolic disorders like hyperlipidemia. Recognized as a popular edible and medicinal mushroom in China and various eastern nations, Ganoderma lucidum is a promising high-value functional and medicinal food with multiple biological activities. Our earlier research has demonstrated that G. lucidum polysaccharides (GLP) showed distinct lipid-lowering abilities by enhancing the response to oxidative stress and inflammation, adjusting bile acid production and lipid regulation factors, and facilitating reverse cholesterol transport through Nrf2-Keap1, NF-κB, LXRα-ABCA1/ABCG1, CYP7A1-CYP27A1, and FXR-FGF15 pathways, hence we delved deeper into the effects of GLP on hyperlipidemia, focusing on its structural characterization, gut microbiota, and fecal metabolites. Our findings showed that GLP changed the composition and structure of gut microbiota, and 10 key biomarker strains screened by LEfSe analysis markedly increased the abundance of energy metabolism, and cell growth and death pathways which were found by PICRUSt2. In addition, GLP intervention significantly altered the fecal metabolites, which enriched in amino acid metabolism and lipid metabolism pathways. The results of structural characterization showed that GLP, with the molecular weight of 12.53 kDa, consisted of pyranose rings and was linked by α-type and β-type glycosidic bonds, and its overall morphology appeared as an irregular flaky structure with some flecks and holes in the surface. Collectively, our study highlighted that the protective effects of GLP were closely associated with the modification of gut microbiota and the regulation of metabolites profiles, thus ameliorating dyslipidemia. Full article

Pesticides have been widely applied in agricultural practices over the past decades to protect crops from pests and other harmful organisms. However, their extensive use results in the contamination of soil, water, and agricultural products, posing significant risks to human and environmental health. Exposure to pesticides can lead to skin irritation, respiratory disorders, and various chronic health problems. Moreover, pesticides frequently enter surface water bodies such as rivers and lakes through agricultural runoff and leaching processes. Therefore, developing effective analytical methods for the rapid and sensitive detection of pesticides in food and water is of great importance. Electrochemical sensing techniques have shown remarkable progress in pesticide analysis due to their high sensitivity, simplicity, and potential for on-site monitoring. Two-dimensional (2D) carbon nanomaterials have emerged as efficient electrocatalysts for the precise and selective detection of pesticides, owing to their large surface area, excellent electrical conductivity, and unique structural features. In this review, we summarize recent advancements in the electrochemical detection of pesticides using 2D carbon-based materials. Comprehensive information on electrode fabrication, sensing mechanisms, analytical performance—including sensing range and limit of detection—and the versatility of 2D carbon composites for pesticide detection is provided. Challenges and future perspectives in developing highly sensitive and selective electrochemical sensing platforms are also discussed, highlighting their potential for simultaneous pesticide monitoring in food and environmental samples. Carbon-based electrochemical sensors have been the subject of many investigations, but their practical application in actual environmental and food samples is still restricted because of matrix effects, operational instability, and repeatability issues. In order to close the gap between laboratory research and real-world applications, this review critically examines sensor performance in real-sample conditions and offers innovative approaches for in situ pesticide monitoring. Full article

Paraneoplastic neurological syndromes (PNSs) are immune-mediated disorders caused by an antitumor response that cross-reacts with the nervous system, leading to severe and often irreversible neurological disability. Once considered exceedingly rare, PNSs are now increasingly recognized owing to the identification of novel neural autoantibodies, wider use of commercial testing, and the emergence of immune checkpoint inhibitor (ICI)-related neurotoxicity that phenotypically overlaps with classic PNS. In this narrative review, we performed a structured search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, without date restrictions, to summarize contemporary advances in the epidemiology, pathogenesis, diagnosis, and management of PNS. Population-based data show rising incidence, largely reflecting improved ascertainment and expanding indications for ICIs. Pathogenetically, we distinguish T-cell-mediated syndromes associated with intracellular antigens from antibody-mediated disorders targeting neuronal surface proteins, integrating emerging concepts of molecular mimicry, tumor genetics, and HLA-linked susceptibility. The 2021 PNS-Care criteria are also reviewed, which replace earlier “classical/non-classical” definitions with risk-stratified phenotypes and antibodies, and demonstrate superior diagnostic performance while underscoring that “probable” and “definite” PNS should be managed with equal urgency. Newly described antibodies and methodological innovations such as PhIP-Seq, neurofilament light chain, and liquid biopsy are highlighted, which refine tumor search strategies and longitudinal monitoring. Management principles emphasize early tumor control, prompt immunotherapy, and a growing repertoire of targeted agents, alongside specific considerations for ICI-associated neurological syndromes. Remaining challenges include diagnostic delays, limited high-level evidence, and the paucity of validated biomarkers of disease activity. Future work should prioritize prospective, biomarker-driven trials and multidisciplinary pathways to shorten time to diagnosis and improve long-term outcomes in patients with PNS. Full article

Transition metal (TM)-doped zinc oxide (ZnO) and zirconium dioxide (ZrO₂) nanocrystals exhibit complex correlations between crystal structure, defect chemistry, vibrational properties, and magnetic behavior that are strongly governed by synthesis route and dopant incorporation mechanisms. This review critically summarizes recent progress on Fe-, Mn-, and Co-doped ZnO and ZrO₂ nanocrystals synthesized by wet chemical, hydrothermal, and microwave-assisted hydrothermal methods, with emphasis on synthesis-driven phase evolution and apparent solubility limits. ZnO and ZrO₂ are treated as complementary host lattices: ZnO is a semiconducting, piezoelectric oxide with narrow solubility limits for most 3d dopants, while ZrO₂ is a dielectric, polymorphic oxide in which transition metal doping may stabilize tetragonal or cubic phases. Structural and microstructural studies using X-ray diffraction, electron microscopy, Raman spectroscopy, and Mössbauer spectroscopy demonstrate that at low dopant concentrations, TM ions may be partially incorporated into the host lattice, giving rise to diluted or defect-mediated magnetic behavior. When solubility limits are exceeded, nanoscopic secondary oxide phases emerge, leading to superparamagnetic, ferrimagnetic, or spin-glass-like responses. Magnetic measurements, including DC magnetization and AC susceptibility, reveal a continuous evolution from paramagnetism in lightly doped samples to dynamic magnetic states characteristic of nanoscale magnetic entities. Vibrational spectroscopy highlights phonon confinement, surface optical phonons, and disorder-activated modes that sensitively reflect nanocrystal size, lattice strain, and defect populations, and often correlate with magnetic dynamics. Rather than classifying these materials as diluted magnetic semiconductors, this review adopts a synthesis-driven and correlation-based framework that links dopant incorporation, local structural disorder, vibrational fingerprints, and magnetic response. By emphasizing multi-technique characterization strategies required to distinguish intrinsic from extrinsic magnetic contributions, this review provides practical guidelines for interpreting magnetism in TM-doped oxide nanocrystals and outlines implications for applications in photocatalysis, sensing, biomedicine, and electromagnetic interference (EMI) shielding. Full article

Analyzing the dynamics of muscle activation patterns and joint range of motion is essential to understanding human movement during complex tasks such as tooth brushing Activities of Daily Living (ADLs). In individuals with neuromotor impairments, accurate assessment of upper limb motor patterns plays a critical role in rehabilitation, supporting the identification of compensatory strategies and informing clinical interventions. This study presents the validation of a previously developed novel, low-cost, wearable, and portable multimodal prototype that integrates inertial measurement units (IMU) and surface electromyography (sEMG) sensors into a single device. The system enables bilateral monitoring of arm segment kinematics and muscle activation amplitudes from six major agonist muscles during ADLs. Eleven healthy participants performed a functional task, tooth brushing, while wearing the prototype. The recorded data were compared with two established gold-standard systems, Qualisys^® motion capture system and Biosignalsplux^®, for validation of kinematic and electrophysiological measurements, respectively. This study provides technical insights into the device’s architecture. The developed system demonstrates potential for clinical and research applications, particularly for monitoring upper limb function and evaluating rehabilitation outcomes in populations with neurological disorders. Full article

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by cutaneous and subcutaneous neurofibromas, which impact quality of life. Dermoscopy-guided high-frequency ultrasound (DG-HFUS) integrates dermoscopy with 33 MHz ultrasound, enabling precise lesion localization and reproducible measurements. Objective: To characterize neurofibromas in NF1 patients using DG-HFUS and identify imaging parameters for diagnosis, monitoring, and treatment planning. Methods: 14 genetically confirmed NF1 patients underwent DG-HFUS imaging (Dermus SkinScanner). 100 neurofibromas were assessed for size, location, shape, contours, surface, echogenicity, global echogenicity, and posterior acoustic features. Results: Lesions were dermal (79%) or subcutaneous (21%), round (28%), ovoid (63%), or spiked (9%). Mean vertical and lateral diameters were 5.37 ± 2.66 mm and 2.28 ± 1.39 mm. All were hypoechoic; 62% homogeneous, 38% heterogeneous. Margins were well-defined in 57% and poorly defined in 43%. Posterior enhancement occurred in 3% and shadowing in 10%. Conclusions: DG-HFUS provides a detailed, reproducible assessment of neurofibromas, supporting differential diagnosis, surgical planning, and longitudinal monitoring. The evaluated imaging parameters offer objective insights for optimizing NF1 management. Future developments, including 3D reconstruction and AI-assisted analysis, may further enhance its clinical utility. Full article

Control of elbow exoskeletons using muscular signals, although promising for the rehabilitation of millions of patients, has not yet been widely commercialized due to challenges in real-time intention estimation and management of dynamic uncertainties. From a practical perspective, millions of patients with stroke, spinal cord injury, or neuromuscular disorders annually require active rehabilitation, and elbow exoskeletons with precise and safe motion intention tracking capabilities can restore functional independence, reduce muscle atrophy, and lower treatment costs. In this research, an intelligent control framework was developed for an elbow joint exoskeleton, designed with the aim of precise and safe real-time tracking of the user’s motion intention. The proposed framework consists of two main stages: (a) real-time estimation of desired joint angle (as a proxy for movement intention) from High-Density Surface Electromyography (HD-sEMG) signals using an LSTM network and (b) implementation and comparison of three PID, impedance, and sliding mode controllers. A public EMG dataset including signals from 12 healthy individuals in four isometric tasks (flexion, extension, pronation, supination) and three effort levels (10, 30, 50 percent MVC) is utilized. After comprehensive preprocessing (Butterworth filter, 50 Hz notch, removal of faulty channels) and extraction of 13 time-domain features with 99 percent overlapping windows, the LSTM network with optimal architecture (128 units, Dropout, batch normalization) is trained. The model attained an RMSE of 0.630 Nm, R² of 0.965, and a Pearson correlation of 0.985 for the full dataset, indicating a 47% improvement in R² relative to traditional statistical approaches, where EMG is converted to desired angle via joint stiffness. An assessment of 12 motion–effort combinations reveals that the sliding mode controller consistently surpassed the alternatives, achieving the minimal tracking errors (average RMSE = 0.21 Nm, R² ≈ 0.96) and showing superior resilience across all tasks and effort levels. The impedance controller demonstrates superior performance in flexion/extension (average RMSE ≈ 0.22 Nm, R² > 0.94) but experiences moderate deterioration in pronation/supination under increased loads, while the classical PID controller shows significant errors (RMSE reaching 17.24 Nm, negative R² in multiple scenarios) and so it is inappropriate for direct myoelectric control. The proposed LSTM–sliding mode hybrid architecture shows exceptional accuracy, robustness, and transparency in real-time intention monitoring, demonstrating promising performance in offline simulation, with potential for real-time clinical applications pending hardware validation for advanced upper-limb exoskeletons in neurorehabilitation and assistive applications. Full article

Background/Objectives: Fibromyalgia (FM) is a chronic pain syndrome often associated with musculoskeletal tenderness, fatigue, and sleep disturbances. Temporomandibular disorders (TMDs) and bruxism are frequently observed comorbidities in patients with FM, yet their objective assessment remains limited. This study aimed to evaluate masticatory muscle activity in patients with fibromyalgia and temporomandibular disorders using both static surface electromyography (sEMG) and a 24 h portable EMG device (Dia-BRUXO^®). Methods: Thirty female patients (mean age 53.6 ± 10.5 years) underwent comprehensive clinical and gnathological evaluations, followed by static EMG recordings of the masseter and temporalis muscles and continuous monitoring of the left masseter over a 24 h period. Results: Results revealed a significantly higher number of bruxism episodes during wakefulness (80.9 ± 130.8) compared to sleep (24.0 ± 26.8; p < 0.0001). The Masseter Time Index (MTI) and Masseter Work Index (MWI) were also significantly higher during wakefulness (p < 0.001), indicating a predominance of daytime masticatory muscle activity. Static sEMG analysis showed generally preserved bilateral muscle symmetry, accompanied by mild imbalances in occlusal load distribution and increased global muscle activation. Conclusions: These findings suggest that patients with fibromyalgia and temporomandibular disorders exhibit increased baseline masticatory muscle activity, particularly during wakefulness, possibly reflecting sustained neuromuscular tension. Continuous EMG monitoring appears to provide an objective tool for characterizing bruxism patterns and complements clinical assessment and self-reported data. However, the absence of a control group and the exclusive inclusion of female patients limit the generalizability of the results. Further studies including appropriate comparison groups are needed to clarify the specificity and clinical implications of these findings. Full article

The objective of the present study was to investigate whether orthodontic treatment alters the morphology and bone mineral density (BMD) distribution of the mandibular condyle in growing adolescent patients. Cone-beam computed tomography (CBCT) images were retrospectively analyzed for 29 patients (10 males and 19 females, aged 12.5 to 17.0 years) treated with full fixed orthodontic appliances. The right and left mandibular condyles were digitally isolated. For the internal control sample, the basal cortical bone (CB) at both mandibular first molar sites was also digitally dissected. A frequency plot of the CBCT gray values, proportional to BMD, was analyzed to calculate the mean and the 5th percentile of low and high gray values (Low₅ and High₅). Morphological changes in the condylar surface were assessed based on temporomandibular joint osteoarthritis (TMJOA) counts. Lateral cephalometric radiographs were used to measure facial morphology parameters and classify skeletal patterns. The cervical vertebral gray values of the same patients were compared. No radiographic signs of TMJ disorder were observed with no significant difference in TMJOA counts between before and after treatment (p = 0.56). The volume, mean and Low₅ gray values of the mandibular condyle, facial morphology parameters, and cervical vertebral gray values significantly increased following orthodontic treatment (p < 0.05). Skeletal Class II patients exhibited greater changes in mean, Low₅, and High₅ mandibular condyle gray values compared to their Class I patients (p < 0.05), whereas cervical vertebral gray values were not significantly influenced by skeletal classification (p > 0.19). The findings suggest that orthodontic treatment, combined with natural patient growth, contributes to nonpathological condylar alterations in adolescent patients. Full article

A common cause of teeth malocclusion and feeding disorders in guinea pigs is macrodontia and odontogenic abscesses. If the maxillary second or third molar teeth are affected, surgical access to them has so far been achieved through enucleation or orbital evisceration due to their location at the base of the orbit. The study aims to demonstrate a transorbital surgical approach to the apices of the maxillary molar teeth (M2 and M3) in guinea pigs, allowing preservation of the eye. Twenty six apicoectomies of maxillary M2 and M3 were performed. The surgical approach involved a skin incision above the zygomatic arch, followed by soft tissue dissection, incision of the orbital ligament, and gentle dorsolateral displacement of the eyeball. Blunt dissection between the lacrimal and zygomatic glands provided direct access to the affected tooth apices, which were removed using a dental bur. After the procedure, the soft tissues and the eye were repositioned and the skin was sutured. All animals recovered uneventfully. The described method may be applied in cases where it is necessary to perform maxillary second and/or last molar tooth apicoectomy while avoiding damage to the eyeball. Care must be taken to protect the corneal surface of the affected eye. Full article

Keratoconjunctivitis sicca (KCS) in dogs is an immune-mediated disorder characterized by aqueous tear deficiency, ocular surface inflammation, and risk of vision loss. Although tear quantity is routinely evaluated using the Schirmer tear test (STT), the accompanying qualitative alterations in tear protein composition remain poorly understood. In this exploratory study, we identified and characterized qualitatively differentially expressed tear proteins in samples collected from seven Beagle dogs with KCS and five healthy Beagles. Samples were collected using filter paper, extracted in phosphate-buffered saline, concentrated by trichloroacetic acid precipitation, and then separated via two-dimensional electrophoresis. Differential protein spots were identified by MALDI-TOF-MS-based peptide mass fingerprinting. Total protein concentrations were determined by measuring UV absorbance at 280 nm and were found to be significantly higher in dogs with KCS (30.7 ± 13.5 mg/mL) than in healthy dogs (11.5 ± 1.8 mg/mL, p < 0.05). Five proteins were identified as differentially expressed: serum albumin, lactotransferrin isoform 1, immunoglobulin gamma heavy chain C, major allergen Can f 1, and lysozyme C. High-molecular-weight proteins were upregulated in KCS, whereas low-molecular-weight proteins (<10 kDa, proline-rich protein-like components) were markedly reduced or absent. These compositional shifts suggest that KCS alters both the quantity and qualitative integrity of the tear proteosome, reflecting impaired tear film homeostasis and diminished ocular surface defense. The results support the potential utility of the tear proteome as a source of diagnostic and therapeutic biomarkers in canine KCS. Full article