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1.
Neural Regen Res ; 20(1): 159-173, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767484

RESUMEN

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

2.
Nanoscale ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847575

RESUMEN

Hierarchical porous carbon is an area of advanced materials that plays a pivotal role in meeting the increasing demands across various industry sectors including catalysis, adsorption, and energy storage and conversion. Additive manufacturing is a promising technique to synthesize architectured porous carbon with exceptional design flexibility, guided by computer-aided precision. This review paper aims to provide an overview of porous carbon derived from various additive manufacturing techniques, including material extrusion, vat polymerization, and powder bed fusion. The respective advantages and limitations of these techniques will be examined. Some exemplary work on various applications will be showcased. Furthermore, perspectives on future research directions, opportunities, and challenges of additive manufacturing for porous carbon will also be offered.

3.
BMJ Neurol Open ; 6(1): e000667, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736583

RESUMEN

Background: In Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor modulators were eligible. Objective: To analyse the roll-out, uptake and real-world efficacy of tixagevimab/cilgavimab in the prevention and severity of COVID-19. To assess compliance with uptake depending on the location of delivery. Methods: We undertook a single-centre study. 440 pwMS and pwNIc were eligible. Logistic regression was used to assess predictors of COVID-19 during follow-up and to assess predictors of uptake among those who consented. Results: Of the eligible pwMS and pwNIc in our service, 52.7% (233/440) requested a consultation and were included in this study. Consultation resulted in 71.7% of people (167/233) receiving the treatment. Of these, 94.0% (157/167) had received three or more COVID-19 vaccines. Among those who received a single dose of tixagevimab/cilgavimab, 19.16% (32/167) tested positive for COVID-19 during the observational window. The majority of these were on ocrelizumab (68.8% (22/32)). None of those with COVID-19 required hospitalisation or supplemental oxygen. There was no difference in odds of COVID-19 during the observation period between those who received and did not receive tixagevimab/cilgavimab (adjusted OR, aOR 2.16 (95% CI 0.82 to 6.85), p=0.43). Uptake of tixagevimab/cilgavimab was highest when offered at the hospital infusion centre (aOR 3.09 (95% CI 1.08 to 9.94) relative to referral to the local pharmacy, p=0.04). Conclusion: Tixagevimab/cilgavimab administration did not protect against subsequent COVID-19 in our cohort. Compliance with uptake was influenced by administration location.

4.
Langmuir ; 40(21): 11251-11262, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38748644

RESUMEN

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

5.
Int J Biol Macromol ; 270(Pt 2): 132433, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38759861

RESUMEN

Nanopore direct RNA sequencing provided a promising solution for unraveling the landscapes of modifications on single RNA molecules. Here, we proposed NanoMUD, a computational framework for predicting the RNA pseudouridine modification (Ψ) and its methylated analog N1-methylpseudouridine (m1Ψ), which have critical application in mRNA vaccination, at single-base and single-molecule resolution from direct RNA sequencing data. Electric signal features were fed into a bidirectional LSTM neural network to achieve improved accuracy and predictive capabilities. Motif-specific models (NNUNN, N = A, C, U or G) were trained based on features extracted from designed dataset and achieved superior performance on molecule-level modification prediction (Ψ models: min AUC = 0.86, max AUC = 0.99; m1Ψ models: min AUC = 0.87, max AUC = 0.99). We then aggregated read-level predictions for site stoichiometry estimation. Given the observed sequence-dependent bias in model performance, we trained regression models based on the distribution of modification probabilities for sites with known stoichiometry. The distribution-based site stoichiometry estimation method allows unbiased comparison between different contexts. To demonstrate the feasibility of our work, three case studies on both in vitro and in vivo transcribed RNAs were presented. NanoMUD will make a powerful tool to facilitate the research on modified therapeutic IVT RNAs and provides useful insight to the landscape and stoichiometry of pseudouridine and N1-pseudouridine on in vivo transcribed RNA species.


Asunto(s)
Seudouridina , Análisis de Secuencia de ARN , Seudouridina/química , Análisis de Secuencia de ARN/métodos , ARN/química , Nanoporos , Redes Neurales de la Computación , Secuenciación de Nanoporos/métodos
6.
Int J Dermatol ; 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38798024

RESUMEN

Eccrine porocarcinoma (EPC) is a rare skin adnexal malignancy with a high potential for metastases. The most common metastatic sites are the lymph nodes and lungs. CCutaneous metastasis is extremely rare, particularly the zosteriform variant, with fewer than 5 cases reported in the literature. Here, we report a unique case of EPC in a 71-year-old male, clinically presenting with multiple clusters of ulcerated nodules distributing as a zosteriform pattern throughout his upper left limb, along with draining lymphatic metastases and lymphedema.

7.
MedComm (2020) ; 5(4): e540, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38606360

RESUMEN

Senile plaque, composed of amyloid ß protein (Aß) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aß aggregates exert age-dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age-gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of ß-amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age-dependent Aß deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age-dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age-dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age-gradient changes in the autophagy-lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

8.
Am J Transl Res ; 16(3): 817-828, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38586098

RESUMEN

OBJECTIVE: This study aims to explore the risk factors of vascular complications following free flap reconstruction and to develop a clinical auxiliary assessment tool for predicting vascular complications in patients undergoing free flap reconstruction leveraging machine learning methods. METHODS: We reviewed the medical data of patients who underwent free flap reconstruction at the Affiliated Hospital of Zunyi Medical University retrospectively from January 1, 2019, to December 31, 2021. Statistical analysis was used to screen risk factors. A training data set was generated and augmented using the synthetic minority oversampling technique. Logistic regression, random forest and neural network, models were trained, using this dataset. The performance of these three predictive models was then evaluated and compared using a test set, with four metrics, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 570 patients who underwent free flap reconstruction were included in this study, 46 of whom developed postoperative vascular complications. Among the models tested, the neural network model exhibited superior performance on the test set, achieving an AUC of 0.828. Multivariate logistic regression analysis identified that preoperative hemoglobin levels, preoperative fibrinogen levels, operation duration, smoking history, the number of anastomoses, and peripheral vascular injury as statistically significant independent risk factors for vascular complications post-free flap reconstruction. The top five predictive factors in the neural network were fibrinogen content, operation duration, donor site, body mass index (BMI), and platelet count. CONCLUSION: Hemoglobin levels, fibrinogen levels, operation duration, smoking history, and anastomotic veins are independent risk factors for vascular complications following free flap reconstruction. These risk factors enhance the ability of machine learning models to predict the occurrence of vascular complications and identify high-risk patients. The neural network model outperformed the logistic regression and random forest models, suggesting its potential to aid clinicians in early identification of high-risk patients thereby mitigating patient suffering and improving prognosis.

9.
Sci Adv ; 10(14): eadl4600, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579006

RESUMEN

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.


Asunto(s)
Genoma , Genómica , Animales , Humanos , Macaca mulatta , Encéfalo
10.
Sci Rep ; 14(1): 9616, 2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671227

RESUMEN

In this study, we aimed to study the role of TCONS_00006091 in the pathogenesis of oral squamous cellular carcinoma (OSCC) transformed from oral lichen planus (OLP). This study recruited 108 OSCC patients which transformed from OLP as the OSCC group and 102 OLP patients with no sign of OSCC as the Control group. ROC curves were plotted to measure the diagnostic values of TCONS_00006091, miR-153, miR-370 and let-7g, and the changes in gene expressions were measured by RT-qPCR. Sequence analysis and luciferase assays were performed to analyze the molecular relationships among these genes. Cell proliferation and apoptosis were observed via MTT and FCM. TCONS_00006091 exhibited a better diagnosis value for OSCC transformed from OLP. OSCC group showed increased TCONS_00006091 expression and decreased expressions of miR-153, miR-370 and let-7g. The levels of SNAI1, IRS and HMGA2 was all significantly increased in OSCC patients. And TCONS_00006091 was found to sponge miR-153, miR-370 and let-7g, while these miRNAs were respectively found to targe SNAI1, IRS and HMGA2. The elevated TCONS_00006091 suppressed the expressions of miR-153, miR-370 and let-7g, leading to the increased expression of SNAI1, IRS and HMGA2. Also, promoted cell proliferation and suppressed apoptosis were observed upon the over-expression of TCONS_00006091. This study demonstrated that the expressions of miR-153, miR-370 and let-7g were down-regulated by the highly expressed TCONS_00006091 in OSCC patients, which accordingly up-regulated the expressions of SNAI1, IRS and HMGA2, resulting in the promoted cell proliferation and suppressed cell apoptosis.


Asunto(s)
Apoptosis , Carcinoma de Células Escamosas , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteína HMGA2 , MicroARNs , Neoplasias de la Boca , Factores de Transcripción de la Familia Snail , Humanos , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Femenino , Masculino , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Apoptosis/genética , Persona de Mediana Edad , Regulación hacia Arriba , Línea Celular Tumoral , Liquen Plano Oral/genética , Liquen Plano Oral/metabolismo , Liquen Plano Oral/patología
11.
Mil Med Res ; 11(1): 21, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605399

RESUMEN

In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.


Asunto(s)
Neoplasias de la Próstata , Análisis de Expresión Génica de una Sola Célula , Masculino , Humanos , Animales , Ratones , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Inmunoterapia , Próstata , Diferenciación Celular
12.
Neuroscience ; 547: 88-97, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38615829

RESUMEN

Down syndrome (DS), also known as trisomy 21, is one of the most common chromosomal disorders associated with intellectual disability. Mouse models are valuable for mechanistic and therapeutic intervention studies. The purpose of this study was to investigate astroglial anomalies in Dp16, a widely used DS mouse model. Brain sections were prepared from one-month-old Dp16 mice and their littermates, immunostained with an anti-GFAP or anti-S100B antibody, and imaged to reconstruct astroglial morphology in three dimensions. No significant difference in the number of astrocytes was found in either the hippocampal CA1 region or cortex between Dp16 and WT mice. However, the average astroglial volume in Dp16 was significantly (P < 0.05) greater than that in WT, suggesting the astroglial activation. Reanalysis of the single-nucleus RNA sequencing data indicated that the genes differentially expressed between WT and Dp16 astrocytes were associated with synapse organization and neuronal projection. In contrast, in vitro cultured neonatal astrocytes did not exhibit significant morphological changes. The expression of Gfap in in vitro cultured Dp16 astrocytes was not increased as it was in in vivo hippocampal tissue. However, after treatment with lipopolysaccharides, the inflammatory response gene IFNß increased significantly more in Dp16 astrocytes than in WT astrocytes. Overall, our results showed that the increase in astrogliogenesis in DS was not apparent in the early life of Dp16 mice, while astrocyte activation, which may be partly caused by increased responses to inflammatory stimulation, was significant. The inflammatory response of astrocytes might be a potential therapeutic target for DS intellectual disability.


Asunto(s)
Astrocitos , Modelos Animales de Enfermedad , Síndrome de Down , Animales , Síndrome de Down/patología , Síndrome de Down/metabolismo , Astrocitos/metabolismo , Astrocitos/patología , Ratones , Células Cultivadas , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/patología , Hipocampo/metabolismo , Ratones Endogámicos C57BL , Encéfalo/patología , Encéfalo/metabolismo
13.
Toxicol Appl Pharmacol ; 486: 116934, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38663673

RESUMEN

The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 h (AUC(0-t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0-∞)), decreased clearance rate (CLz/F), and prolonged terminal half-life (t1/2). In contrast, a slight inhibition was observed in saxagliptin metabolism when concomitantly used with macitentan, as no pharmacokinetic parameters were altered, except for CLz/F. Thus, dosage adjustment of saxagliptin may be required in combination with sildenafil to achieve safe therapeutic plasma concentrations and reduce the risk of potential toxicity, but it is not necessary for co-administration with macitentan.


Asunto(s)
Adamantano , Dipéptidos , Interacciones Farmacológicas , Pirimidinas , Citrato de Sildenafil , Sulfonamidas , Citrato de Sildenafil/farmacocinética , Citrato de Sildenafil/farmacología , Sulfonamidas/farmacocinética , Sulfonamidas/farmacología , Dipéptidos/farmacocinética , Dipéptidos/farmacología , Pirimidinas/farmacocinética , Pirimidinas/farmacología , Humanos , Adamantano/análogos & derivados , Adamantano/farmacocinética , Adamantano/farmacología , Masculino , Animales , Citocromo P-450 CYP3A/metabolismo , Simulación del Acoplamiento Molecular , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología
14.
Nucleic Acids Res ; 52(9): 4830-4842, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38634812

RESUMEN

We present m6ACali, a novel machine-learning framework aimed at enhancing the accuracy of N6-methyladenosine (m6A) epitranscriptome profiling by reducing the impact of non-specific antibody enrichment in MeRIP-Seq. The calibration model serves as a genomic feature-based classifier that refines the identification of m6A sites, distinguishing those genuinely present from those that can be detected in in-vitro transcribed (IVT) control experiments. We find that m6ACali effectively identifies non-specific binding peaks reported by exomePeak2 and MACS2 in novel MeRIP-Seq datasets without the need for paired IVT controls. The model interpretation revealed that off-target antibody binding sites commonly occur at short exons and short mRNAs, originating from high read coverage regions that share the motif sequence with true m6A sites. We also reveal that the ML strategy can efficiently adjust differentially methylated peaks and other antibody-dependent, base-resolution m6A detection techniques. As a result, m6ACali offers a promising method for the universal enhancement of m6A profiles generated by MeRIP-Seq experiments, elevating the benchmark for omics-level m6A data integration.


Asunto(s)
Adenosina , Aprendizaje Automático , Adenosina/análogos & derivados , Humanos , Calibración , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN/métodos , Metilación , Transcriptoma
15.
Food Chem ; 450: 139386, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38653057

RESUMEN

This study aimed at using α-L-arabinofuranosidase CcABF to improve the clarity and active substances in fermented ginkgo kernel juice by artificial neural network (ANN) modeling and genetic algorithm (GA) optimization. A credible three-layer feedforward ANN model was established to predict the optimal parameters for CcABF clarification. The experiments proved the highest transmittance of 89.40% for fermented ginkgo kernel juice with this understanding, which exhibited a 25.56% increase over the unclarified group. With the clarification of CcABF, the antioxidant capacity in juice was enhanced with the increase of total phenolic and flavone contents, and the maximum DPPH and hydroxyl radical scavenging rates were increased by 89.71% and 26.65%, respectively. The contents of toxic ginkgolic acids declined markedly, while the active ingredients of ginkgetin and ginkgolide B showed a modest increase. Moreover, changes in free amino acids and volatile compounds improved the nutritive value and flavor of clarified fermented ginkgo kernel juice.


Asunto(s)
Fermentación , Jugos de Frutas y Vegetales , Ginkgo biloba , Glicósido Hidrolasas , Redes Neurales de la Computación , Ginkgo biloba/química , Jugos de Frutas y Vegetales/análisis , Glicósido Hidrolasas/metabolismo , Glicósido Hidrolasas/química , Algoritmos , Antioxidantes/química , Antioxidantes/análisis , Antioxidantes/metabolismo , Manipulación de Alimentos
16.
Soc Cogn Affect Neurosci ; 19(1)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38597901

RESUMEN

Empathy can be divided into two core components, cognitive empathy (CE) and affective empathy (AE), mediated by distinct neural networks. Deficient empathy is a central feature of autism spectrum conditions (ASCs), but it is unclear if this deficit results from disruption solely within empathy networks or from disrupted functional integration between CE and AE networks. To address this issue, we measured functional connectivity (FC) patterns both within and between empathy networks in autistic children (4-8 years, n = 31) and matched typically developing (TD) children (n = 26) using near-infrared spectroscopy during the presentation of an animated story evoking CE and AE. Empathy and social communication ability were also assessed using the Empathy Quotient/Systemizing Quotient (EQ/SQ) and Social Responsiveness Scale, respectively. The results showed that the FC in the AE network of autistic children did not differ from the TD group across conditions; however, the ASC group showed weaker FC in the CE network under the CE condition and weaker FC between networks when processing AE information, the latter of which was negatively correlated with EQ scores in ASC. The empathy defect in ASC may involve abnormal integration of CE and AE network activities under AE conditions.


Asunto(s)
Trastorno Autístico , Empatía , Espectroscopía Infrarroja Corta , Humanos , Empatía/fisiología , Masculino , Niño , Preescolar , Femenino , Trastorno Autístico/psicología , Trastorno Autístico/fisiopatología , Cognición/fisiología , Encéfalo/fisiopatología , Vías Nerviosas/fisiopatología , Vías Nerviosas/fisiología , Mapeo Encefálico
17.
Artículo en Inglés | MEDLINE | ID: mdl-38453478

RESUMEN

BACKGROUND: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. METHODS: Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). RESULTS: A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. CONCLUSION: In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

18.
Sci Rep ; 14(1): 5672, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453995

RESUMEN

The mix proportion of multi-source coal-based solid waste (CSW) for underground backfilling affects transportation and support performance of backfill materials, and even the backfilling cost. In this study, the optimal mix proportion of desulfurization gypsum (DG), furnace bottom slag (FBS) and gasification fine slag (GFS) is determined by the Response Surface Methodology-Box Behnken Design (RSM-BBD). Then the fluidity, bleeding rate, 3-day strength, 7-day strength and preparation cost are evaluation indicators, the optimal mix proportion of backfill materials is determined by the multi-objective decision-making method (MDM). Finally, the microstructure of the backfill material with optimal mix proportion was studied by TGA, MIP, SEM-EDS and XRD. The results show that the mix proportion of CSW with the optimal comprehensive index is coal gangue (CG): coal fly ash (CFA): DG: FBS: GFS = 1:1.5:0.2:0.1:0.1, the mass concentration is 78%, and ordinary Portland cement (OPC)/CSW = 7.5%. The weight loss phenomenon of the backfill material with the optimal mix proportion occurs continuously during the heating process, mainly due to the evaporation of crystal water, structural water and hydroxyl water. There are dense narrow-necked pores in the backfill material, and the pore connectivity is poor. There is no hydration reaction occurs between CSW particles, and the strength increase of the backfill material mainly depends on the hydration reaction of cement. In ettringite, part of Al2O3 is replaced by SiO2, and part of CaSO4 is replaced by CaCO3. This study provides a reference for the engineering application of underground backfilling with multi-source CSW.

19.
Front Neurosci ; 18: 1355512, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550568

RESUMEN

Introduction: Recently, the microstate analysis method has been widely used to investigate the temporal and spatial dynamics of electroencephalogram (EEG) signals. However, most studies have focused on EEG at resting state, and few use microstate analysis to study emotional EEG. This paper aims to investigate the temporal and spatial patterns of EEG in emotional states, and the specific neurophysiological significance of microstates during the emotion cognitive process, and further explore the feasibility and effectiveness of applying the microstate analysis to emotion recognition. Methods: We proposed a KLGEV-criterion-based microstate analysis method, which can automatically and adaptively identify the optimal number of microstates in emotional EEG. The extracted temporal and spatial microstate features then served as novel feature sets to improve the performance of EEG emotion recognition. We evaluated the proposed method on two publicly available emotional EEG datasets: the SJTU Emotion EEG Dataset (SEED) and the Database for Emotion Analysis using Physiological Signals (DEAP). Results: For the SEED dataset, 10 microstates were identified using the proposed method. These temporal and spatial features were fed into AutoGluon, an open-source automatic machine learning model, yielding an average three-class accuracy of 70.38% (±8.03%) in subject-dependent emotion recognition. For the DEAP dataset, the method identified 9 microstates. The average accuracy in the arousal dimension was 74.33% (±5.17%) and 75.49% (±5.70%) in the valence dimension, which were competitive performance compared to some previous machine-learning-based studies. Based on these results, we further discussed the neurophysiological relationship between specific microstates and emotions, which broaden our knowledge of the interpretability of EEG microstates. In particular, we found that arousal ratings were positively correlated with the activity of microstate C (anterior regions of default mode network) and negatively correlated with the activity of microstate D (dorsal attention network), while valence ratings were positively correlated with the activity of microstate B (visual network) and negatively correlated with the activity of microstate D (dorsal attention network). Discussion: In summary, the findings in this paper indicate that the proposed KLGEV-criterion-based method can be employed to research emotional EEG signals effectively, and the microstate features are promising feature sets for EEG-based emotion recognition.

20.
Org Lett ; 26(11): 2243-2248, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38456736

RESUMEN

The preparation of polycyclic aromatic hydrocarbons (PAHs) by the Scholl reaction is typically performed by using superstoichiometric oxidants. Herein, we develop an electrochemical continuous-flow Scholl reaction to access PAHs that features a reduction in the use of supporting electrolytes and easy scale-up without changing the reaction conditions and setups. This reaction allows the synthesis of distorted PAHs containing three [5]helicene units that possess intriguing electronic and optical properties.

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