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1.
Epilepsia Open ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325042

RESUMO

OBJECTIVE: Dystonic posturing (DP) is a common semiology in temporal lobe epilepsy (TLE). We aimed to explore cerebellar gradient alterations in functional connectivity in TLE patients with and without DP. METHODS: Resting-state functional MRI data were obtained in 60 TLE patients and 32 matched healthy controls. Patients were further divided into two groups: TLE with DP (TLE + DP, 31 patients) and TLE without DP (TLP-DP, 29 patients). We explored functional gradient alterations in the cerebellum based on cerebellar-cerebral functional connectivity and combined with independent component analysis to evaluate cerebellar-cerebral functional integration and reveal the contribution of the motor components to the gradient. RESULTS: There were no obvious differences in clinical features and postoperative seizure outcomes between TLE + DP and TLE-DP patients. Patients and controls all showed a clear unimodal-to-transmodal gradient transition in the cerebellum, while TLE patients demonstrated an extended principal gradient in functional connectivity compared to healthy controls, which was more limited in TLE + DP patients. Gradient alterations were more widespread in TLE-DP patients, involving bilateral cerebellum, while gradient alterations in TLE + DP patients were limited in the cerebellum ipsilateral to the seizure focus. In addition, more cerebellar motor components contributed to the gradient alterations in TLE + DP patients, mainly in ipsilateral cerebellum. SIGNIFICANCE: Extended cerebellar principal gradients in functional connectivity revealed excessive functional segregation between unimodal and transmodal systems in TLE. The functional connectivity gradients were more limited in TLE + DP patients. Functional connectivity in TLE patients with dystonic posturing involved more contribution of cerebellar motor function to ipsilateral cerebellar gradient. PLAIN LANGUAGE SUMMARY: Dystonic posturing contralateral to epileptic focus is a common symptom in temporal lobe epilepsy, and the cerebellum may be involved in its generation. In this study, we found cerebellar gradients alterations in functional connectivity in temporal lobe epilepsy patients with and without contralateral dystonic posturing. In particular, we found that TLE patients with dystonic posturing may have more limited cerebellar gradient in functional connectivity, involving more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Our study suggests a close relationship between ipsilateral cerebellum and contralateral dystonic posturing.

2.
J Cancer Res Clin Oncol ; 150(9): 426, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39299959

RESUMO

BACKGROUND: Double-hit lymphoma (DHL) with c-MYC gene translocation is highly aggressive and has a poor prognosis. In DHL cells, activation-induced cytidine deaminase (AID) promotes antibody class switch recombination (CSR), ultimately leading to c-MYC gene translocation caused by Myc/IgH DNA double-strand breaks. However, currently there is still no method to suppress the expression of AID. METHODS: In this study, we compared the clinical significance of AID expression in DHL, Additionally, two human double-hit lymphoma cell lines were used to analyze the effect of imatinib mesylate on c-MYC in vitro, and the therapeutic effect was also evaluated in xenograft mouse models. RESULTS: Imatinib mesylate downregulated the AID and c-MYC proteins in patients with chronic myelogenous leukemia associated with DHL. In addition, imatinib mesylate reduced AID and c-MYC expression in SU-DHL-4 and OCI-Ly18 DHL cells. Imatinib mesylate exerted significant inhibitory effects on the proliferation and metastasis of SU-DHL-4 and OCI-Ly18 cells. Finally, imatinib mesylate reduced not only tumor burden in DHL mouse models, but also AID and c-MYC expression in vivo. CONCLUSION: These findings reveal that imatinib mesylate effectively reduces the carcinogenic function of c-MYC in DHL, providing novel strategies for developing therapies targeting c-MYC-driven DHL.


Assuntos
Citidina Desaminase , Mesilato de Imatinib , Proteínas Proto-Oncogênicas c-myc , Ensaios Antitumorais Modelo de Xenoenxerto , Mesilato de Imatinib/farmacologia , Animais , Humanos , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Linhagem Celular Tumoral , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Feminino , Antineoplásicos/farmacologia , Translocação Genética , Masculino , Proliferação de Células/efeitos dos fármacos , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfoma/genética , Linfoma/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
Eur J Pharm Biopharm ; 200: 114327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759900

RESUMO

P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.


Assuntos
Neoplasias da Mama , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Lipossomos , Camundongos Endogâmicos BALB C , Feminino , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Camundongos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Células MCF-7 , Fragmentos de Peptídeos/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Colágeno Tipo IV
4.
Int J Neural Syst ; 34(7): 2450031, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38623649

RESUMO

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.


Assuntos
Córtex Cerebral , Eletroencefalografia , Imageamento por Ressonância Magnética , Rede Nervosa , Esquizofrenia , Tálamo , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Tálamo/fisiopatologia , Tálamo/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Adulto , Masculino , Feminino , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Ondas Encefálicas/fisiologia , Adulto Jovem , Vias Neurais/fisiopatologia , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Conectoma
5.
CNS Neurosci Ther ; 30(4): e14672, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38644561

RESUMO

AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Descanso , Convulsões , Humanos , Masculino , Feminino , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Descanso/fisiologia , Adulto Jovem , Convulsões/fisiopatologia , Convulsões/diagnóstico por imagem , Pessoa de Meia-Idade , Mapeamento Encefálico , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/farmacologia , Adolescente , Atividade Motora/fisiologia , Atividade Motora/efeitos dos fármacos
6.
Comput Biol Med ; 171: 108200, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428099

RESUMO

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has led to significant global morbidity and mortality, with potential neurological consequences, such as Parkinson's disease (PD). However, the underlying mechanisms remain elusive. METHODS: To address this critical question, we conducted an in-depth transcriptome analysis of dopaminergic (DA) neurons in both COVID-19 and PD patients. We identified common pathways and differentially expressed genes (DEGs), performed enrichment analysis, constructed protein‒protein interaction networks and gene regulatory networks, and employed machine learning methods to develop disease diagnosis and progression prediction models. To further substantiate our findings, we performed validation of hub genes using a single-cell sequencing dataset encompassing DA neurons from PD patients, as well as transcriptome sequencing of DA neurons from a mouse model of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced PD. Furthermore, a drug-protein interaction network was also created. RESULTS: We gained detailed insights into biological functions and signaling pathways, including ion transport and synaptic signaling pathways. CD38 was identified as a potential key biomarker. Disease diagnosis and progression prediction models were specifically tailored for PD. Molecular docking simulations and molecular dynamics simulations were employed to predict potential therapeutic drugs, revealing that genistein holds significant promise for exerting dual therapeutic effects on both PD and COVID-19. CONCLUSIONS: Our study provides innovative strategies for advancing PD-related research and treatment in the context of the ongoing COVID-19 pandemic by elucidating the common pathogenesis between COVID-19 and PD in DA neurons.


Assuntos
COVID-19 , Doença de Parkinson , Animais , Camundongos , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/uso terapêutico , Simulação de Acoplamento Molecular , Pandemias , SARS-CoV-2 , Modelos Animais de Doenças
7.
Int J Neural Syst ; 34(4): 2450017, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372049

RESUMO

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node-node and edge-edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques.


Assuntos
Mapeamento Encefálico , Epilepsia Generalizada , Epilepsia , Humanos , Mapeamento Encefálico/métodos , Epilepsia/diagnóstico por imagem , Eletroencefalografia/métodos , Imageamento por Ressonância Magnética/métodos , Cerebelo/diagnóstico por imagem , Imunoglobulina E , Encéfalo
8.
Hum Brain Mapp ; 45(1): e26551, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063289

RESUMO

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high-level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello-cerebral circuit is still poorly understood. Resting-state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel-based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello-cerebral functional integration on the voxel-based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello-cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.


Assuntos
Epilepsia Generalizada , Imageamento por Ressonância Magnética , Humanos , Vias Neurais , Mapeamento Encefálico/métodos , Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/patologia , Córtex Cerebral/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Imunoglobulina E
9.
Bioengineering (Basel) ; 10(10)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37892896

RESUMO

Hierarchical functional structure plays a crucial role in brain function. We aimed to investigate how aging affects hierarchical functional structure and to evaluate the relationship between such effects and molecular, microvascular, and cognitive features. We used resting-state functional magnetic resonance imaging (fMRI) data from 95 older adults (66.94 ± 7.23 years) and 44 younger adults (21.8 ± 2.53 years) and employed an innovative graph-theory-based analysis (stepwise functional connectivity (SFC)) to reveal the effects of aging on hierarchical functional structure in the brain. In the older group, an SFC pattern converged on the primary sensory-motor network (PSN) rather than the default mode network (DMN). Moreover, SFC decreased in the DMN and increased in the PSN at longer link-steps in aging, indicating a reconfiguration of brain hub systems during aging. Subsequent correlation analyses were performed between SFC values and molecular, microvascular features, and behavioral performance. Altered SFC patterns were associated with dopamine and serotonin, suggesting that altered hierarchical functional structure in aging is linked to the molecular fundament with dopamine and serotonin. Furthermore, increased SFC in the PSN, decreased SFC in the DMN, and accelerated convergence rate were all linked to poorer microvascular features and lower executive function. Finally, a mediation analysis among SFC features, microvascular features, and behavioral performance indicated that the microvascular state may influence executive function through SFC features, highlighting the interactive effects of SFC features and microvascular state on cognition.

10.
Geriatr Nurs ; 54: 192-198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37801874

RESUMO

This study aims to investigate the status and influencing factors of two-way social support among old adults. A cross-sectional study of 408 convenient samples of old adults was conducted using socio-demographic questionnaire, Brief 2-Way Social Support Scale, Modified Barthel index, General Well-being Schedule, Family APGAR Index, and Lubben Social Network Scale 6. The two-way social support score for old adults in China was (43.74±7.86), with the receiving and giving social support scoring (22.80±4.06) and (20.94±4.52), respectively. The multiple linear regression analysis revealed that family care, residence place, socioeconomic status, and social network were associated with both receiving and giving social support. Chronic diseases and religious beliefs were related to receiving social support, while gender, general well-being, and residence form were related to giving social support. Tailored interventions based on the distinct influencing factors are needed to enhance old adults' social support both as recipients and providers.


Assuntos
Apoio Social , Humanos , Estudos Transversais , Fatores Socioeconômicos , China , Inquéritos e Questionários
11.
Schizophr Bull ; 49(6): 1554-1567, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37607339

RESUMO

BACKGROUND AND HYPOTHESIS: Schizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia and whether these link to molecular genetics. STUDY DESIGN: We systematically searched Web of Science, PubMed, and BrainMap for the amplitude of low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, regional cerebral blood flow, and voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, and illness duration-dependent meta-analyses were performed using the activation likelihood estimation algorithm. Subsequently, Spearman correlation and partial least squares regression analyses were conducted to assess the relationship between identified reliable convergent patterns of multimodality and neurotransmitter/transcriptome, using prior molecular imaging and brain-wide gene expression. STUDY RESULTS: In total, 203 experiments comprising 10 613 patients and 10 461 healthy controls were included. Multimodal meta-analysis showed that brain regions of significant convergence in schizophrenia were mainly distributed in the frontotemporal cortex, anterior cingulate cortex, insula, thalamus, striatum, and hippocampus. Interestingly, the analyses of illness-duration subgroups identified aberrant functional and structural evolutionary patterns: Lines from the striatum to the cortical core networks to extensive cortical and subcortical regions. Subsequently, we found that these robust multimodal neuroimaging abnormalities were associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, and GABAergic systems. CONCLUSIONS: This work links transcriptome/neurotransmitters with reliable structural and functional signatures of brain abnormalities underlying disease effects in schizophrenia, which provides novel insight into the understanding of schizophrenia pathophysiology and targeted treatments.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Imageamento por Ressonância Magnética/métodos , Transcriptoma , Encéfalo , Neuroimagem
12.
Int J Older People Nurs ; 18(5): e12569, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37574788

RESUMO

OBJECTIVES: Elder self-neglect is a global public health problem, and older people admitted to the hospital may have a higher risk of self-neglect due to their deteriorating health conditions. This study aimed to translate, adapt and validate the Abrams geriatric self-neglect assessment scale (AGSS) among older Chinese people admitted to the hospital. METHODS: Data were derived from a cross-sectional survey of a convenience sample of 452 older people admitted to a general hospital. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the structural validity of the AGSS. Content validity, criterion validity, internal consistency reliability, and test-retest reliability were also conducted to assess the psychometric properties of the scale. RESULTS: EFA yielded a 6-item one-factor model, which was supported by CFA and explained 44.74% of the total variance. The internal consistency was acceptable (Cronbach α = 0.740), and the test-retest reliability with a 14-day interval was good (intraclass correlation coefficient, ICC = 0.966). Significantly positive correlations with the caregiver-rated elder self-neglect assessment scale (r = 0.648) supported the concurrent validity of the scale. Significant differences in scores between respondents with different ages, marital statuses, educational levels and numbers of chronic diseases demonstrated the discriminative validity. CONCLUSION: The Chinese version of the AGSS is an easy-to-use, reliable and valid measure with satisfactory psychometric properties. Future studies should recruit a more representative sample of older people in China to verify the applicability of the scale. IMPLICATIONS FOR PRACTICE: The Chinese version of the AGSS enables clinical staff to accurately screen for and assess elder self-neglect upon hospital admission, which can inform the development of specific interventions and assignment of additional guardianship to those at risk of elder self-neglect.


Assuntos
Avaliação Geriátrica , Autonegligência , Idoso , Humanos , China , Estudos Transversais , Hospitais , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Hospitalização , Traduções
13.
NPJ Parkinsons Dis ; 9(1): 117, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491350

RESUMO

Peripheral immune cells play a vital role in the development of Parkinson's disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naïve patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests included t-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-1ß, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-α played an important role in cognitive impairment. Intracellular TNF-α levels in the naïve CD8+ T-cell cluster C16 (CD57- naïve CD8+ T) and natural killer (NK) cell cluster C32 (CD57- CD28- NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-α and decreased interferon-γ expression in C16 correlated with increased Unified Parkinson's Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8+ T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.

14.
Epilepsia Open ; 8(3): 1038-1048, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37394869

RESUMO

OBJECTIVE: To investigate potential functional and structural large-scale network disturbances in untreated patients with generalized tonic-clonic seizures (GTCS) and the effects of antiseizure drugs. METHODS: In this study, 41 patients with GTCS, comprising 21 untreated patients and 20 patients who received antiseizure medications (ASMs), and 29 healthy controls were recruited to construct large-scale brain networks based on resting-state functional magnetic resonance imaging and diffusion tensor imaging. Structural and functional connectivity and network-level weighted correlation probability (NWCP) were further investigated to identify network features that corresponded to response to ASMs. RESULTS: Untreated patients showed more extensive enhancement of functional and structural connections than controls. Specifically, we observed abnormally enhanced connections between the default mode network (DMN) and the frontal-parietal network. In addition, treated patients showed similar functional connection strength to that of the control group. However, all patients exhibited similar structural network alterations. Moreover, the NWCP value was lower for connections within the DMN and between the DMN and other networks in the untreated patients; receiving ASMs could reverse this pattern. SIGNIFICANCE: Our study identified alterations in structural and functional connectivity in patients with GTCS. The influence of ASMs may be more noticeable within the functional network; moreover, abnormalities in both the functional and structural coupling state may be improved by ASM treatment. Therefore, the coupling state of structural and functional connectivity may be used as an indicator of the efficacy of ASMs.


Assuntos
Mapeamento Encefálico , Imagem de Tensor de Difusão , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Convulsões/tratamento farmacológico , Encéfalo/diagnóstico por imagem
15.
BMC Med ; 21(1): 237, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400838

RESUMO

BACKGROUND: Schizophrenia is characterized by complex psychiatric symptoms and unclear pathological mechanisms. Most previous studies have focused on the morphological changes that occur over the development of the disease; however, the corresponding functional trajectories remain unclear. In the present study, we aimed to explore the progressive trajectories of patterns of dysfunction after diagnosis. METHODS: Eighty-six patients with schizophrenia and 120 healthy controls were recruited as the discovery dataset. Based on multiple functional indicators of resting-state brain functional magnetic resonance imaging, we conducted a duration-sliding dynamic analysis framework to investigate trajectories in association with disease progression. Neuroimaging findings were associated with clinical symptoms and gene expression data from the Allen Human Brain Atlas database. A replication cohort of patients with schizophrenia from the University of California, Los Angeles, was used as the replication dataset for the validation analysis. RESULTS: Five stage-specific phenotypes were identified. A symptom trajectory was characterized by positive-dominated, negative ascendant, negative-dominated, positive ascendant, and negative surpassed stages. Dysfunctional trajectories from primary and subcortical regions to higher-order cortices were recognized; these are associated with abnormal external sensory gating and a disrupted internal excitation-inhibition equilibrium. From stage 1 to stage 5, the importance of neuroimaging features associated with behaviors gradually shifted from primary to higher-order cortices and subcortical regions. Genetic enrichment analysis identified that neurodevelopmental and neurodegenerative factors may be relevant as schizophrenia progresses and highlighted multiple synaptic systems. CONCLUSIONS: Our convergent results indicate that progressive symptoms and functional neuroimaging phenotypes are associated with genetic factors in schizophrenia. Furthermore, the identification of functional trajectories complements previous findings of structural abnormalities and provides potential targets for drug and non-drug interventions in different stages of schizophrenia.


Assuntos
Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Encéfalo/patologia , Progressão da Doença
16.
Cereb Cortex ; 33(14): 9095-9104, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37231204

RESUMO

Schizophrenia is a self-disorder characterized by disrupted brain dynamics and architectures of multiple molecules. This study aims to explore spatiotemporal dynamics and its association with psychiatric symptoms. Resting-state functional magnetic resonance imaging data were collected from 98 patients with schizophrenia. Brain dynamics included the temporal and spatial variations in functional connectivity density and association with symptom scores were evaluated. Moreover, the spatial association between dynamics and receptors/transporters according to prior molecular imaging in healthy subjects was examined. Patients demonstrated decreased temporal variation and increased spatial variation in perceptual and attentional systems. However, increased temporal variation and decreased spatial variation were revealed in higher order networks and subcortical networks in patients. Specifically, spatial variation in perceptual and attentional systems was associated with symptom severity. Moreover, case-control differences were associated with dopamine, serotonin and mu-opioid receptor densities, serotonin reuptake transporter density, dopamine transporter density, and dopamine synthesis capacity. Therefore, this study implicates the abnormal dynamic interactions between the perceptual system and cortical core networks; in addition, the subcortical regions play a role in the dynamic interaction among the cortical regions in schizophrenia. These convergent findings support the importance of brain dynamics and emphasize the contribution of primary information processing to the pathological mechanism underlying schizophrenia.


Assuntos
Esquizofrenia , Humanos , Dopamina , Serotonina , Imageamento por Ressonância Magnética/métodos , Encéfalo , Mapeamento Encefálico/métodos
17.
J Phys Condens Matter ; 35(32)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37137313

RESUMO

The mixed-phase MoS2(1T/2H MoS2) with heterostructure exhibited high catalytic activity. The specific ratios of 1T/2H could exhibit optimal performance in various applications. Therefore, more methods need be developed for synthesizing 1T/2H mixed-phase MoS2. Herein, a viable route was studied for the phase transition of 1T/2H MoS2regulated by H+. Briefly, the commercially available bulk MoS2was used to obtain 1T/2H MoS2via chemical intercalation of Li+. Then the residual Li+around 1T/2H MoS2was replaced by H+in acidic electrolytes, owing to the extremely higher charge-to-volume ratio of H+. Thus, the thermodynamically unstable 1T phase lost the protection of residual Li+and could be re-transforming into the relatively stable 2H phase. The change of the 2H/(2H+1T) ratio was measured using novel extinction spectroscopy, which provides a rapid identification method in comparison with x-ray photoelectron spectroscopy (XPS). The experimental results revealed that the concentration of H+influenced the phase transition velocity of MoS2. In particular, the phase transition from 1T to 2H phase in the H+solution was faster at the beginning, and the higher the H+concentration in an acidic solution, the faster the increase in 2H content. For an instant, the ratio of the 2H phase was increased by 7.08% in an acidic solution (CH+= 2.00 M) after 1 h, which was several times greater than the case in the distilled water. This finding provides a promising method to easily obtain different ratios of 1T/2H MoS2, which is beneficial for further development of catalytic performance especially in energy generation and storage.

18.
J Neurosci Res ; 101(7): 1188-1199, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36866516

RESUMO

Working memory (WM) is a cognitive function involving emergent properties of theta oscillations and large-scale network interactions. The synchronization of WM task-related networks in the brain enhanced WM performance. However, how these networks regulate WM processing is not well known, and the alteration of the interaction among these networks may play an important role in patients with cognitive dysfunction. In this study, we used simultaneous EEG-fMRI to examine the features of theta oscillations and the functional interactions among activation/deactivation networks during the n-back WM task in patients with idiopathic generalized epilepsy (IGE). The results showed that there was more enhancement of frontal theta power along with WM load increase in IGE, and the theta power was positively correlated with the accuracy of the WM tasks. Moreover, fMRI activations/deactivations correlated with n-back tasks were estimated, and we found that the IGE group had increased and widespread activations in high-load WM tasks, including the frontoparietal activation network and task-related deactivation areas, such as the default mode network and primary visual and auditory networks. In addition, the network connectivity results demonstrated decreased counteraction between the activation network and deactivation network, and the counteraction was correlated with the higher theta power in IGE. These results indicated the important role of the interactions between activation and deactivation networks during the WM process, and the unbalance among them may indicate the pathophysiological mechanism of cognitive dysfunction in generalized epilepsy.


Assuntos
Epilepsia Generalizada , Memória de Curto Prazo , Humanos , Memória de Curto Prazo/fisiologia , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Epilepsia Generalizada/diagnóstico por imagem , Eletroencefalografia/métodos , Imunoglobulina E
19.
Small Methods ; 7(3): e2201529, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36683170

RESUMO

Molybdenum disulfide (MoS2 ) is considered as one of the most promising non-noble-metal catalysts for hydrogen evolution reaction (HER). To achieve practical application, introducing sulfur (S) vacancies on the inert basal plane of MoS2 is a widely accepted strategy to improve its HER activity. However, probing active sites at the nanoscale and quantitatively analyzing the related electrocatalytic activity in electrolyte aqueous solution are still great challenges. In this work, utilizing high-resolution scanning electrochemical microscopy, optimized electrodes and newly designed thermal drift calibration software, the HER activity of the S vacancies on an MoS2 inert surface is in situ imaged with less than 20-nm-radius sensitivity and the HER kinetic data for S vacancies, including Tafel plot and onset potential, are quantitatively measured. Additionally, the stability of S vacancies over the wide range of pH 0-13 is investigated. This study provides a viable strategy for obtaining the catalytic kinetics of nanoscale active sites on structurally complex electrocatalysts and evaluating the stability of defects in different environments for 2D material-based catalysts.

20.
Hum Brain Mapp ; 44(6): 2323-2335, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36692056

RESUMO

Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in adults. Although brain myelination alterations have been observed in TLE, it remains unclear how the myelination network changes in TLE. This study developed a novel method in characterization of myelination structural covariance network (mSCN) by T1-weighted and T2-weighted magnetic resonance imaging (MRI). The mSCNs were estimated in 42 left TLE (LTLE), 42 right TLE (RTLE) patients, and 41 healthy controls (HCs). The topology of mSCN was analyzed by graph theory. Voxel-wise comparisons of myelination laterality were also examined among the three groups. Compared to HC, both patient groups showed decreased myelination in frontotemporal regions, amygdala, and thalamus; however, the LTLE showed lower myelination in left medial temporal regions than RTLE. Moreover, the LTLE exhibited decreased global efficiency compared with HC and more increased connections than RTLE. The laterality in putamen was differently altered between the two patient groups: higher laterality at posterior putamen in LTLE and higher laterality at anterior putamen in RTLE. The putamen may play a transfer station role in damage spreading induced by epileptic seizures from the hippocampus. This study provided a novel workflow by combination of T1-weighted and T2-weighted MRI to investigate in vivo the myelin-related microstructural feature in epileptic patients first time. Disconnections of mSCN implicate that TLE is a system disorder with widespread disruptions at regional and network levels.


Assuntos
Epilepsia do Lobo Temporal , Adulto , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Bainha de Mielina , Mapeamento Encefálico , Lobo Temporal , Imageamento por Ressonância Magnética/métodos , Lateralidade Funcional
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