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Individual variability in functional connectivity underlies individual differences in cognition and behaviors, yet its association with functional specialization in the auditory cortex remains elusive. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, this study was designed to investigate the spatial distribution of auditory cortex individual variability in its whole-brain functional network architecture. An inherent hierarchical axis of the variability was discerned, which radiates from the medial to lateral orientation, with the left auditory cortex demonstrating more pronounced variations than the right. This variability exhibited a significant correlation with the variations in structural and functional metrics in the auditory cortex. Four auditory cortex subregions, which were identified from a clustering analysis based on this variability, exhibited unique connectional fingerprints and cognitive maps, with certain subregions showing specificity to speech perception functional activation. Moreover, the lateralization of the connectional fingerprint exhibited a U-shaped trajectory across the subregions. These findings emphasize the role of individual variability in functional connectivity in understanding cortical functional organization, as well as in revealing its association with functional specialization from the activation, connectome, and cognition perspectives.
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Corteza Auditiva , Conectoma , Humanos , Corteza Auditiva/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Conectoma/métodos , Encéfalo , CogniciónRESUMEN
Controlling the excessive inflammatory response is one of the key ways to reduce the severity and mortality of severe influenza virus infections. RAGE is involved in inflammatory responses and acute lung injuries. Here, we investigated the role of RAGE and its potential application as a target for severe influenza treatment through serological correlation analysis for influenza patients, and treatment with the RAGE inhibitor FPS-ZM1 on A549 cells or mice with influenza A (H1N1) infection. The results showed high levels of RAGE were correlated with immunopathological injury and severity of influenza, and FPS-ZM1 treatment increased the viability of A549 cells with influenza A infection and decreased morbidity and mortality of influenza A virus infection in mice. The RAGE/NF-κb inflammatory signaling pathway is a major targeting pathway for FPS-ZM1 treatment in severe influenza. These findings provide further insights into the immune injury of severe influenza and a potential targeting candidate for the disease treatment.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Humanos , Ratones , Animales , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Benzamidas/farmacologíaRESUMEN
The corpus callosum (CC) is the principal white matter bundle supporting communication between the two brain hemispheres. Despite its importance, a comprehensive mapping of callosal connections is still lacking. Here, we constructed the first bidirectional population-based callosal connectional atlas between the midsagittal section of the CC and the cerebral cortex of the human brain by means of diffusion-weighted imaging tractography. The estimated connectional topographic maps within this atlas have the most fine-grained spatial resolution, demonstrate histological validity, and were reproducible in two independent samples. This new resource, a complete and comprehensive atlas, will facilitate the investigation of interhemispheric communication and come with a user-friendly companion online tool (CCmapping) for easy access and visualization of the atlas.
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Corteza Cerebral , Cuerpo Calloso , Humanos , Adulto Joven , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo , Mapeo Encefálico/métodosRESUMEN
The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta4C3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta4C3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus (MRSA) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta4C3 NSs enhance dendritic cell activation, further triggering T helper 1 (TH1)/TH2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.
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Death due to severe influenza is usually a fatal complication of a dysregulated immune response more than the acute virulence of an infectious agent. Although spleen tyrosine kinase (SYK) as a critical immune signaling molecule and therapeutic target plays roles in airway inflammation and acute lung injury, the role of SYK in influenza virus infection is not clear. Here, we investigated the antiviral and anti-inflammatory effects of SYK inhibitor R406 on influenza infection through a coculture model of human alveolar epithelial (A549) and macrophage (THP-1) cell lines and mouse model. The results showed that R406 treatment increased the viability of A549 and decreased the pathogenicity and mortality of lethal influenza virus in mice with influenza A infection, decreased levels of intracellular signaling molecules under the condition of inflammation during influenza virus infection. Combination therapy with oseltamivir further ameliorated histopathological damage in the lungs of mice and further delayed the initial time to death compared with R406 treatment alone. This study demonstrated that phosphorylation of SYK is involved in the pathogenesis of influenza, and R406 has antiviral and anti-inflammatory effects on the treatment of the disease, which may be realized through multiple pathways, including the already reported SYK/STAT/IFNs-mediated antiviral pathway, as well as TNF-α/SYK- and SYK/Akt-based immunomodulation pathway.
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Antiinflamatorios , Antivirales , Modelos Animales de Enfermedad , Infecciones por Orthomyxoviridae , Oxazinas , Quinasa Syk , Animales , Humanos , Quinasa Syk/antagonistas & inhibidores , Ratones , Antivirales/farmacología , Antivirales/uso terapéutico , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/inmunología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Oxazinas/farmacología , Oxazinas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Imidazoles/farmacología , Imidazoles/uso terapéutico , Pulmón/patología , Pulmón/virología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Células A549 , Virus de la Influenza A/efectos de los fármacos , Ratones Endogámicos BALB C , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Gripe Humana/tratamiento farmacológico , Gripe Humana/inmunología , Células THP-1 , Femenino , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
With the rapid development of portable and wearable electronic devices, there is an increasing demand for miniaturized and lightweight energy storage devices. Micro-supercapacitors (MSCs), as a kind of energy storage device with high power density, a fast charge/discharge rate, and a long service life, have attracted wide attention in the field of energy storage in recent years. The performance of MSCs is mainly related to the electrodes, so there is a need to explore more efficient methods to prepare electrodes for MSCs. The process is cumbersome and time-consuming using traditional fabrication methods, and the development of laser micro-nano technology provides an efficient, high-precision, low-cost, and convenient method for fabricating supercapacitor electrodes, which can achieve finer mask-less nanofabrication. This work reviews the basics of laser fabrication of MSCs, including the laser system, the structure of MSCs, and the performance evaluation of MSCs. The application of laser micro-nanofabrication technology to MSCs and the integration of MSCs are analyzed. Finally, the challenges and prospects for the development of laser micro-nano technology for manufacturing supercapacitors are summarized.
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BACKGROUND & AIMS: Growing evidence suggests that neurotransmitters may be associated with cognitive decline in MDD. This study primarily investigated the differences in cognitive functions between MDD patients and healthy controls, and explored the potential association between neurotransmitters and cognitive function of MDD patients. METHODS: This cross-sectional study enrolled 87 first-diagnosed and drug-naïve patients with MDD and 50 healthy controls. Neurotransmitters (glutamine, glutamic acid, γ-2Aminobutiric acid, kainate, vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid, dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane, kynurenine, 5-HT, 5-hydroxyindoleacetic acid) were measured using LC-MS/MS and cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Then associative analyses with adjustment (female, age, BMI, education) by multiple linear regression between neurotransmitters and cognitive functions especially in MDD patients were performed. RESULTS: MDD patients had lower RBANS scores in immediate memory, delayed memory and RBANS scores after adjustment. Neurotransmitters were associated with the cognitive levels of MDD patients after adjustment: DOPAC and DOPAC/DA had positive association with immediate memory score; DOPAC, DOPAC/DA and (VMA+MHPG)/NE were positively associated with attention score; NE was negatively associated with language score; DOPAC/DA was positively associated with both delayed memory and RBANS scores. CONCLUSION: Patients had greater cognitive impairment especially in memory. Furthermore, plasma neurotransmitter may be related to MDD and play an important role in cognitive impairment in MDD, especially in memory and attention.