Search Results (247)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Refractory high-entropy alloys (HEAs) are promising candidates for next-generation nuclear applications, particularly fusion reactors, due to their excellent high-temperature mechanical properties and irradiation resistance. Here, the microstructure and mechanical behavior were investigated for an equimolar WTaTiVZr HEA, designed from a palette of low-activation elements. The as-cast alloy exhibited a dendritic microstructure composed of W-Ta rich dendrites and Zr-Ti-V rich inter-dendritic regions, both possessing a body-centered cubic (BCC) crystal structure. Room temperature bulk compression tests showed ultra-high strength of around 1.6 GPa and plastic strain ~6%, with fracture surfaces showing cleavage facets. The alloy also demonstrated excellent high-temperature strength of ~650 MPa at 500 °C. Scratch-based fracture toughness was ~38 MPa√m for the as-cast WTaTiVZr HEA compared to ~25 MPa√m for commercially used pure tungsten. This higher value of fracture toughness indicates superior damage tolerance relative to commercially used pure tungsten. These results highlight the alloy’s potential as a low-activation structural material for high-temperature plasma-facing components (PFCs) in fusion reactors. Full article

Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex/anterior cingulate cortex (dmPFC/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 ± 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 ± 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann–Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD. Full article

This study addresses the unclear mechanisms by which preferential flow channels (PFCs), formed during long-term waterflooding, affect nano-gel microsphere (NGM) flooding efficiency, utilizing CMG reservoir numerical simulation software. A dynamic evolution model of PFCs was established by coupling CROCKTAB (stress–porosity hysteresis) and CROCKTABW (water saturation-driven permeability evolution), and the deep flooding mechanism of NGMs (based on their gel properties such as swelling, elastic deformation, and adsorption, and characterized by a “plugging-migration-replugging” process) was integrated. The results demonstrate that neglecting PFCs overestimates recovery by 8.7%, while NGMs reduce permeability by 33% (from 12 to 8 mD) in high-conductivity zones via “bridge-plug-filter cake” structures, diverting flow to low-permeability layers (+33% permeability, from 4.5 to 6 mD). Field application in a Chang 6 tight reservoir (permeability variation coefficient 0.82) confirms a >10-year effective period with 0.84% incremental recovery (from 7.31% to 8.15%) and favorable economics (ROI ≈ 10:1), providing a theoretical and engineering framework for gel-based conformance control in analogous reservoirs. Full article

Transcranial direct current stimulation (tDCS) modulates cortical excitability, thus inducing improvements in motor learning of simple tasks. In this study, we aimed to evaluate the effect of different tDCS conditions—anodal stimulation over the motor cortex (M1), anodal and cathodal stimulation over the prefrontal cortex (PFC), and sham—on the online and offline learning of a complex accuracy task (golf-putting) in novice golfers. Methods: A total of 40 young, healthy subjects (24 men, 16 women) without previous golf experience were randomly distributed in four groups receiving sham, anodal M1, anodal PFC or cathodal PFC tDCS. All subjects participated in two consecutive sessions. In the first session, they performed 15 blocks of 10 golf-putting along with tDCS stimulation. After 24 h, they performed the same task without tDCS. Results: Repeated measures ANOVA revealed a significant improvement in performance during the two consecutive golf-putting sessions regardless of the site and the stimulation conditions. Conclusion: Our findings suggest that tDCS over M1 or PFC does not confer additional benefits in the acquisition of complex, full-body motor skills such as golf-putting. Full article

Objective: Burning mouth syndrome (BMS) is a chronic and often debilitating orofacial pain condition characterized by a burning sensation in the oral mucosa without clear abnormal lesions. While its etiology is considered multifactorial, the underlying pathophysiology remains unclear. This narrative review aims to synthesize existing functional magnetic resonance imaging (fMRI) studies to shed light on the central neural mechanisms contributing to BMS. Methods: A focused electronic search was conducted across the PubMed and J-STAGE databases for relevant articles published in English from January 2000 to May 2025. The review prioritized studies investigating brain structure and function using fMRI in individuals with BMS. Results: Our synthesis of the literature consistently demonstrated that the brains of individuals with BMS exhibit augmented connectivity within the medial pain system and a diminished gray matter volume in the medial prefrontal cortex (mPFC). These findings suggest a crucial role for altered brain circuitry, particularly a reduction in the output of the basal ganglia dopamine system, in the experience of BMS pain. Conclusions: The consistent fMRI findings strongly indicate that BMS involves significant functional and structural brain alterations. The observed changes in the mPFC and its connections to the basal ganglia dopamine system highlight this pathway as a potential target for both pharmacological and non-pharmacological neurological interventions for individuals with BMS. Full article

In order to examine the fracture development law of overlying strata in goafs and to reasonably lay out a high gas-drainage roadway under gob-side entry retaining with roadside filling, the 91–105 working face of the Wangzhuang Coal Mine was selected as the engineering case study. The failure laws and fracture development characteristics of the overlying strata in both the strike and dip directions using gob-side entry retaining and roadside filling were studied through rock mechanic tests and PFC numerical simulations. The optimal layout of the high gas-drainage roadway was determined through theoretical analysis and coupled Fluent–PFC numerical simulations, and on-site monitoring was conducted to evaluate the extraction effects. The results indicate that the first weighting interval of the 91–105 working face was 40 m, while the periodic weighting interval was approximately 14 m. The height of the falling zone was 14.4 m, and the height of the gas-conducting fracture zone was 40.7 m. In the dip direction, compared with coal pillar retaining, gob-side entry retaining with roadside filling formed an inverted trapezoid secondary breaking zone above the retaining roadway. Using this method, the span of the separation zone increased to 30 m, and the collapse angle decreased to 52°, resulting in a shift in the separation zone—the primary space for gas migration—toward the goaf. It was determined that the optimal location of the high gas-drainage roadway was 28 m above the coal roof and 30 m horizontally from the return air roadway. Compared with the 8105 working face, this position was 10 m closer toward the goaf. On-site gas extraction monitoring data indicate that, at this optimized position, the gas concentration in the high gas-drainage roadway increased by 22%, and the net gas flow increased by 18%. Full article

Depression and obesity are comorbid conditions linked through shared neuroinflammatory and immune mechanisms. This study examined the effects of chronic cannabidiol (CBD) treatment on behavior and neuroinflammatory gene expression in female rats exposed to a combined model of high-fat diet (HFD) and unpredictable chronic mild stress (UCMS). Rats were subjected to an acute HFD for 2 weeks, followed by 4 weeks of UCMS. CBD (10 mg/kg, i.p.) or vehicle was administered during the final 2 weeks of UCMS. Specifically, mRNA levels of nuclear factor kappa B1 (NF-κB1), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were measured in the ventromedial prefrontal cortex (vmPFC) and CA1. CBD’s effects varied depending on the type of stressor. It promoted coping behavior, increased locomotion, reduced freezing, and restored UCMS-induced depressive-like behavior in a splash test. In the vmPFC, CBD normalized the HFD- and UCMS-induced increase in il1β, and downregulated nfkb1 and tnfa expression. In the CA1, it normalized stress-induced downregulation in nfkb1 expression. These findings suggest that the efficacy of CBD in modulating both behavior and neuroinflammation is contingent upon the nature of the stress exposure, highlighting its potential as a targeted treatment for stress-related neuropsychiatric disorders in females. Full article

Shallow landslides are one of the main geological hazards that occur during heavy rainfall in Yuexi County every year, posing potential risks to the personal and property safety of local residents. A rainfall-induced shallow landslide named Baishizu No. 15 landslide in Yuexi Country was taken as a case study. Based on the field geological investigation, combined with physical and mechanical experiments in laboratory as well as numerical simulation, the failure mechanism induced by rainfall infiltration was studied, and the movement process after landslide failure was inverted. The results show that the pore-water pressure within 2 m of the landslide body increases significantly and the factory of safety (F_s) has a good corresponding relationship with rainfall, which decreased to 0.978 after the heavy rainstorm on July 5 and July 6 in 2020. The maximum shear strain and displacement are concentrated at the foot and front edge of the landslide, which indicates a “traction type” failure mode of the Baishizu No. 15 landslide. In addition, the maximum displacement during landslide instability is about 0.5 m. The residual strength of soils collected from the soil–rock interface shows significant rate-strengthening, which ensures that the Baishizu No. 15 landslide will not exhibit high-speed and long runout movement. The rate-dependent friction coefficient of sliding surface was considered to simulate the movement process of the Baishizu No. 15 landslide by using PFC^2D. The simulation results show that the movement velocity exhibited obvious oscillatory characteristics. After the movement stopped, the landslide formed a slip cliff at the rear edge and deposited as far as the platform at the front of the slope foot but did not block the road ahead. The final deposition state is basically consistent with the on-site investigation. The research results of this paper can provide valuable references for the disaster prevention, mitigation, and risk assessment of shallow landslides on residual soil slopes in the Dabie mountainous region. Full article

In cold-region rock engineering, freeze–thaw cycle-induced crack propagation in fractured rock masses serves as a major cause of disasters such as slope instability. Existing studies primarily focus on the influence of individual fissure parameters, yet lack a systematic analysis of the crack propagation mechanisms under the coupled action of multiple parameters. To address this, we establish three groups of slope models with different rock bridge distances (d), rock bridge angles (α), and fissure angles (β) based on the PFC2D discrete element method. Frost heave loads are simulated by incorporating the volumetric expansion during water–ice phase change. The Parallel Bond Model (PBM) is used to capture the mechanical behavior between particles and the bond fracture process. This reveals the crack evolution laws under freeze–thaw cycles. The results show that, at a short rock bridge distance of d = 60 m, stress concentrates in the fracture zone. This easily leads to the rapid penetration of main cracks and triggers sudden instability. At a long rock bridge distance where d ≥ 100 m, the degree of stress concentration decreases. Meanwhile, the stress distribution range expands, promoting multiple crack initiation points and the development of branch cracks. The number of cracks increases as the rock bridge distance grows. In cases where the rock bridge angle is α ≤ 60°, stress is more likely to concentrate in the fracture zone. The crack propagation exhibits strong synergy, easily forming a penetration surface. When α = 75°, the stress concentration areas become dispersed and their distribution range expands. Cracks initiate earliest at this angle, with the largest number of cracks forming. Cumulative damage is significant under this condition. When the fissure angle is β = 60°, stress concentration areas gather around the fissures. Their distribution range expands, making cracks easier to propagate. Crack propagation becomes more dispersed in this case. When β = 30°, the main crack rapidly penetrates due to stress concentration, inhibiting the development of branch cracks, and the number of cracks is the smallest after freeze–thaw cycles. When β = 75°, the freeze–thaw stress dispersion leads to insufficient driving force, and the number of cracks is 623. The research findings provide a theoretical foundation for assessing freeze–thaw damage in fractured rock masses of cold regions and for guiding engineering stability control from a multi-parameter perspective. Full article

Prenatal cannabis exposure (PCE) has been associated with altered prefrontal cortex (PFC) activity and connectivity in adulthood, potentially increasing the risk of psychopathology later in life. This risk is thought to involve a complex interplay between the endocannabinoid and dopaminergic systems. We investigated the transcriptional regulation of genes associated with these systems in an animal model of PCE during adolescence, focusing on DNA methylation and specific microRNAs (miRNAs). Our study revealed increased mRNA levels of dopamine D1 and D2 receptors (Drd1 and Drd2) in the PFC, with a notable effect on Drd2 in male offspring. Notably, we observed a consistent reduction in Drd2 DNA methylation levels in PCE male rats. Both Drd1 and Drd2 expressions were regulated by selective miRNAs. Accordingly, we found changes in the excitability of PFC pyramidal neurons in male adolescent PCE offspring, along with alterations in the Netrin-1/DCC guidance cue system. Our findings highlight PCE-induced modifications of the PFC dopaminergic system while maintaining stable gene expression of the endocannabinoid system in male offspring. Changes in this complex interaction during sensitive developmental periods like adolescence might lead to sex-dependent divergent behavioral outcomes induced by PCE. Full article

Background/Objectives: While the presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon aortic valve stenosis (AS) has been performed yet. The hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods: Murine wire injury (WI) to induce AS, or sham surgery, were performed prior to the 4-week assessment of AS severity, left ventricular (LV) function and hypertrophy with echocardiography (echo). Organ weights, levels of leukocytes, cytokines and costimulatory molecules in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes), and immune cell uptake of Cy5-labelled perfluorocarbon nanoemulsions were measured. Results: Trends towards correlation were found between organ weights, myocardial immune cells and echo. Cytokine mRNA levels trended mainly towards an increase in heart and regional lymph nodes and a reduction in spleen and liver, and correlation with echo was more homogeneous after WI. Unchanged cytokine protein levels in myocardium and plasma trended to correlate with echo. A homogeneous pattern was found for echo and costimulatory molecule correlation, while PFC uptake by lymphatic cells was reduced upon AS. Conclusions: The results suggest a link between number and activation state of leukocytes in peripheral organs and cardiac processes in AS. Considering the pathological value of inflammation, it is crucial that future studies investigate if a modulation of the systemic inflammatory reaction relieves severity of AS and opposes development of heart failure. Full article

Effective stored-grain insect pest detection is crucial in grain storage management to prevent economic losses and ensure food security throughout production and supply chains. Existing detection methods suffer from issues such as high labor costs, environmental interference, high equipment costs, and inconsistent performance. To address these limitations, we proposed PDA-YOLO, an improved stored-grain insect pest detection algorithm based on YOLO11n which integrates three key modules: PoolFormer_C3k2 (PF_C3k2) for efficient local feature extraction, Attention-based Intra-Scale Feature Interaction (AIFI) for enhanced global context awareness, and Dynamic Multi-scale Aware Edge (DMAE) for precise boundary detection of small targets. Trained and tested on 6200 images covering five common stored-grain insect pests (Lesser Grain Borer, Red Flour Beetle, Indian Meal Moth, Maize Weevil, and Angoumois Grain Moth), PDA-YOLO achieved an mAP@0.5 of 96.6%, mAP@0.5:0.95 of 60.4%, and F1 score of 93.5%, with a computational cost of only 6.9 G and mean detection time of 9.9 ms per image. These results demonstrate the advantages over mainstream detection algorithms, balancing accuracy, computational efficiency, and real-time performance. PDA-YOLO provides a reference for pest detection in intelligent grain storage management. Full article

Background/Objectives: Despite the growing recognition of cognitive disengagement syndrome (CDS), previously termed sluggish cognitive tempo, as a distinct dimension of psychopathology, the neural correlates of CDS remain largely unknown. We investigated the neural correlates of CDS in children using whole-head magnetoencephalography (MEG). Methods: A community-based sample of children (N = 43, ages 8–12 years) was recruited and completed self-report ratings of CDS. MEG was recorded while the children completed an adapted version of the attention network test (ANT). Results: The results indicated that higher levels of self-reported CDS symptoms were associated with larger changes in the root-mean square (ΔRMS) (incongruent—congruent trials) in M2 and M3, suggesting children with higher levels of CDS symptoms might require greater mental effort to overcome distractors during incongruent trials. The source localization analysis initially revealed a negative correlation between child self-reported CDS symptoms and ΔM2 power (incongruent—congruent trials) in the medial prefrontal cortex (mPFC), suggesting insufficient power allocation in a region critical for attentional processing. However, this association was no longer significant after controlling for ADHD status. No significant correlation was found between self-reported CDS symptoms and alerting or orienting. Conclusions: These findings provide initial evidence of the disrupted attentional processing associated with CDS in children. Further replication and extension with larger samples are warranted. Full article

Background/Objectives: Norepinephrine (NE) plays a crucial role in modulating cognitive processes via α2A-adrenoceptors (α2A-ARs) within the prefrontal cortex (PFC), an essential brain region responsible for higher cognitive functions. The α2A-ARs are found on both postsynaptic and presynaptic membranes in the PFC. Previous studies have shown that presynaptic α2A-ARs, predominantly located at NE terminals, function as autoreceptors that inhibit NE release. However, the expression of α2A-ARs at non-NE terminals, such as glutamate and GABA, remains ambiguous. To clarify the expression patterns and potential roles of α2A-ARs at non-NE terminals, we investigated their presence at the axon terminals of excitatory glutamate neurons and inhibitory GABA neurons in the rat PFC using immunofluorescence double-labeling, whole-cell patch-clamp recordings, and pharmacological approaches. Methods: To clarify the expression patterns and potential roles of α2A-ARs at non-NE terminals, we investigated their presence at the axon terminals of glutamate neurons and GABA neurons in the rat PFC using immunofluorescence double-labeling, whole-cell patch-clamp recordings, and pharmacological approaches. Results: Our findings delineated the distribution of α2A-ARs at the axon terminals of both glutamate and GABA neurons, and the expression of α2A-AR in the pyramidal neurons within the rat PFC as well. Furthermore, we employed the selective α2A-AR agonist guanfacine to assess the functional role of presynaptic α2A-ARs at these non-NE terminals. Following the application of the PKA inhibitor PKI_5–24 to block postsynaptic α2A-AR function, guanfacine still significantly decreased the frequency (not the amplitude) of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in layer 5–6 pyramidal neurons. Notably, the frequency reduction induced by guanfacine persisted even after the depletion of presynaptic NE vesicles. Conclusions: These findings offer a comprehensive analysis of presynaptic α2A-AR expression and function in the PFC, revealing for the first time their role as heteroreceptors that modulate the release of glutamate and GABA. Our results provide morphological and electrophysiological insights into a potential mechanism through which α2A-AR stimulation enhances cognitive functions. Full article