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1.
J Magn Reson Imaging ; 58(6): 1882-1891, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37118972

RESUMO

BACKGROUND: The combination of radiomics and diffusion tensor imaging (DTI) may have potential clinical value in the early stage of HIV-associated neurocognitive disorders (HAND). PURPOSE: To investigate the value of DTI-based radiomics in the early stage of HAND in people living with HIV (PLWH). STUDY TYPE: Retrospective. POPULATION: A total of 138 male PLWH were included, including 68 with intact cognition (IC) and 70 with asymptomatic neurocognitive impairment (ANI). Seventy healthy controls (HCs) were recruited for tract-based spatial statistics (TBSS) analysis. All PLWHs were randomly divided into training and validation cohorts at a 7:3 ratio. FIELD STRENGTH/SEQUENCE: A 3 T, single-shot spin-echo echo planar imaging (EPI). ASSESSMENT: The differences between the PLWH groups were compared using TBSS and region of interest (ROI) analysis. Radiomic features were extracted from the corpus callosum (CC) on DTI postprocessed images, including fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The performance of the radiomic signatures was evaluated by ROC curve analysis. The radiomic signature with the highest area under the curve (AUC) was combined with clinical characteristics to construct a nomogram. Decision curve analysis (DCA) was performed to evaluate the ability of different methods in discriminating ANI. STATISTICAL TESTS: Chi-square test, independent-samples t test, Kruskal-Wallis test, Mann-Whitney U test, threshold-free cluster enhancement (TFCE), ROC curve analysis, DCA, multivariate logistic regression analysis, Hosmer-Lemeshow test. P < 0.05 with TFCE corrected and P < 0.0001 without TFCE corrected were considered statistically significant. RESULTS: The ANI group showed lower FA and higher AD than the IC group. In the validation cohort, the AUCs of the FA-, AD-, MD- and RD-based radiomic signatures and the clinicoradiomic nomogram were 0.829, 0.779, 0.790, 0.864, and 0.874, respectively. DCA revealed that the nomogram was of greater clinical value than TBSS analysis, the clinical models, and the RD-based radiomic signature. DATA CONCLUSION: The combination of DTI and radiomics is correlated with early stage of HAND in PLWH. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.


Assuntos
Imagem de Tensor de Difusão , Infecções por HIV , Humanos , Masculino , Imagem de Tensor de Difusão/métodos , HIV , Estudos Retrospectivos , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/complicações , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Diagnóstico Precoce
2.
Neuroimage ; 242: 118473, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34390876

RESUMO

OBJECTIVE: The age-related changes in the resting-state networks (RSNs) exhibited temporally specific patterns in humans, and humans and rhesus monkeys have similar RSNs. We hypothesized that the RSNs in rhesus monkeys experienced similar developmental patterns as humans. METHODS: We acquired resting-state fMRI data from 62 rhesus monkeys, which were divided into childhood, adolescence, and early adulthood groups. Group independent component analysis (ICA) was used to identify monkey RSNs. We detected the between-group differences in the RSNs and static, dynamic, and effective functional network connections (FNCs) using one-way variance analysis (ANOVA) and post-hoc analysis. RESULTS: Eight rhesus RSNs were identified, including cerebellum (CN), left and right lateral visual (LVN and RVN), posterior default mode (pDMN), visuospatial (VSN), frontal (FN), salience (SN), and sensorimotor networks (SMN). In internal connections, the CN, SN, FN, and SMN mainly matured in early adulthood. The static FNCs associated with FN, SN, pDMN primarily experienced fast descending slow ascending type (U-shaped) developmental patterns for maturation, and the dynamic FNCs related to pDMN (RVN, CN, and SMN) and SMN (CN) were mature in early adulthood. The effective FNC results showed that the pDMN and VSN (stimulated), SN (inhibited), and FN (first inhibited then stimulated) chiefly matured in early adulthood. CONCLUSION: We identified eight monkey RSNs, which exhibited similar development patterns as humans. All the RSNs and FNCs in monkeys were not widely changed but fine-tuned. Our study clarified that the progressive synchronization, exploration, and regulation of cognitive RSNs within the pDMN, FN, SN, and VSN denoted potential maturation of the RSNs throughout development. We confirmed the development patterns of RSNs and FNCs would support the use of monkeys as a best animal model for human brain function.


Assuntos
Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Animais , Feminino , Macaca mulatta/crescimento & desenvolvimento , Masculino , Descanso/fisiologia
3.
J Integr Neurosci ; 19(2): 285-293, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706192

RESUMO

Speech therapy has been widely used as an essential therapy for compensatory articulation errors in nonsyndromic cleft lip and palate patients. We sought to identify potential biomarkers of nonsyndromic cleft lip and palate children after speech rehabilitation based on resting-state fMRI and graph theory techniques. We scanned 28 nonsyndromic cleft lip and palate and 28 typically developing children for resting-state fMRI on a 3T MRI scanner. Functional networks were constructed, and their topological properties were obtained for assessing between-group differences (two-sample t-tests). Also, language clear degree scale scores were obtained for correlation analysis with the topological features in nonsyndromic cleft lip and palate patients. Significant between-group differences of local properties were detected in brain regions involved in higher-order language and social cognition. There were no significant correlations between topological feature differences and language clear degree scale scores in nonsyndromic cleft lip and palate patients. Graph theory provided valuable insight into the neurobiological mechanisms of speech rehabilitation in nonsyndromic cleft lip and palate patients. The global network features, small-world index, nodal clustering coefficient, and nodal shortest path length may represent potential imaging biomarkers for the estimation of effective speech rehabilitation.


Assuntos
Transtornos da Articulação , Fenda Labial/complicações , Fissura Palatina/complicações , Conectoma , Giro do Cíngulo/fisiopatologia , Rede Nervosa/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Fonoterapia , Transtornos da Articulação/diagnóstico por imagem , Transtornos da Articulação/etiologia , Transtornos da Articulação/fisiopatologia , Transtornos da Articulação/terapia , Pré-Escolar , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Idioma , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Cognição Social
4.
Neuroradiology ; 61(1): 63-70, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30298188

RESUMO

PURPOSE: Previous studies have investigated the brain structural abnormalities in children with type I Gaucher disease (GD). The purpose of our study is to investigate the topological efficiency of the brain functional network in children with type 1 GD. METHODS: Twenty-two children diagnosed with type 1 GD and 22 sex- and age-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) examination. For longitudinal study, the GD patients underwent rs-fMRI examination again after 4.6 years. Graph theoretical analysis was used to assess the brain network topological properties at the global and regional levels. RESULTS: Compared with the HCs, the children with type 1 GD showed a decreased efficiency in functional segregation with a decreased γ (normalized clustering coefficient). In addition, the balance between functional segregation and integration was disrupted with decreased small-worldness (σ). At the regional level, the children with type 1 GD showed significantly decreased nodal degree and efficiency in the right precentral gyrus (PreCG.R) and left postcentral gyrus (PoCG.L). The significantly altered γ, σ, and nodal degree in the PreCG.R and PoCG.L were negatively correlated with the disease duration. No significant alterations in the global and regional topological properties were identified in these patients over time. CONCLUSION: Compared with that of the HCs, the efficiency of the brain functional network in the children with type 1 GD was disrupted, and regional involvement was located in motor- and sensory-related regions. The efficiency of the brain functional network in these patients remained stable over time.


Assuntos
Mapeamento Encefálico/métodos , Doença de Gaucher/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Feminino , Doença de Gaucher/patologia , Humanos , Interpretação de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Rede Nervosa/patologia
5.
Inorg Chem ; 56(4): 1771-1774, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28140578

RESUMO

Herein, we report the synthesis and atomic structures of the cluster-assembled CuxAu25-x(PPh3)10(PhCH2CH2S)5Cl22+ and Cu3Au34(PPh3)13(tBuPhCH2S)6S23+ nanoclusters (NCs). The atomic structures of both NCs were precisely determined by single-crystal X-ray crystallography. The CuxAu25-x(PPh3)10(PhC2H4S)5Cl22+ NC was assembled by two icosahedral M13 via a vertex-sharing mode. The Cu atom partially occupies the top and waist sites and is monocoordinated with chlorine or thiol ligands. Meanwhile, the Cu3Au34(PPh3)13(tBuPhCH2S)6S23+ NC can be described as three 13-atom icosahedra sharing three vertexes in a cyclic fashion. The three Cu atoms all occupy the internal positions of the cluster core. What is more important is that all three Cu atoms in Cu3Au34 are monocoordinated by the bare S atoms. The absorption spectra of the as-synthesized bimetallic NCs reveal that the additional metal doping and different cluster assemblies affect the electronic structure of the monometallic NCs.

6.
Adv Sci (Weinh) ; 11(18): e2310163, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460167

RESUMO

Intrinsic immunosuppressive tumor microenvironment (ITM) and insufficient tumor infiltration of T cells severely impede the progress of glioblastoma (GBM) immunotherapy. In this study, it is identify that inhibiting the expression of glucose transporter 1 (GLUT1) can facilitate the prevention of lactate excretion from tumor glycolysis, which significantly alleviates the lactate-driven ITM by reducing immunosuppressive tumor-associated macrophages (TAMs) and regulatory T cells (Tregs). Simultaneously, the findings show that the generated inflammatory cytokine IFN-γ during immune activation aggravates the immune escape by upregulating immune checkpoint programmed death-ligand 1 (PD-L1) in tumor cells and TAMs. Therefore, an injectable thermogel loaded with a GLUT1 inhibitor BAY-876 and a PD-1/PD-L1 blocker BMS-1 (Gel@B-B) for dual-regulation of metabolism and immunity of GBM is developed. Consequently, in situ injection of Gel@B-B significantly delays tumor growth and prolongs the survival of the orthotopic GBM mouse model. By actively exposing tumor antigens to antigen-presenting cells, the GBM vaccine combined with Gel@B-B is found to significantly increase the fraction of effector T cells (Th1/CTLs) in the tumor microenvironment, thereby remarkably mitigating tumor recurrence long-term. This study may provide a promising strategy for GBM immunotherapy.


Assuntos
Antígeno B7-H1 , Glioblastoma , Imunoterapia , Ácido Láctico , Animais , Humanos , Camundongos , Antígeno B7-H1/imunologia , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Géis , Glioblastoma/imunologia , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Ácido Láctico/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos
7.
Comput Biol Med ; 172: 108243, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484694

RESUMO

OBJECTIVE: This study aimed to develop and evaluate a machine learning model utilizing non-invasive clinical parameters for the classification of endometrial non-benign lesions, specifically atypical hyperplasia (AH) and endometrioid carcinoma (EC), in postmenopausal women. METHODS: Our study collected clinical parameters from a cohort of 999 patients with postmenopausal endometrial lesions and conducted preprocessing to identify 57 relevant characteristics from these irregular clinical data. To predict the presence of postmenopausal endometrial non-benign lesions, including atypical hyperplasia and endometrial cancer, we employed various models such as eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), Back Propagation Neural Network (BPNN), as well as two ensemble models. Additionally, a test set was performed on an independent dataset consisting of 152 patients. The performance evaluation of all models was based on metrics including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F1 score. RESULTS: The RF model demonstrated superior recognition capabilities for patients with non-benign lesions compared to other models. In the test set, it attained a sensitivity of 88.1% and an AUC of 0.93, surpassing all alternative models evaluated in this study. Furthermore, we have integrated this model into our hospital's Clinical Decision Support System (CDSS) and implemented it within the outpatient electronic medical record system to continuously validate and optimize its performance. CONCLUSIONS: We have trained a model and deployed a system with high discriminatory power that may provide a novel approach to identify patients at higher risk of postmenopausal endometrial non-benign lesions who may benefit from more tailored screening and clinical intervention.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Pós-Menopausa , Humanos , Feminino , Hiperplasia , Benchmarking , Aprendizado de Máquina
8.
Brain Imaging Behav ; 17(5): 530-540, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37433970

RESUMO

OBJECTIVES: The alterations in cerebellar activity that occur in vascular mild cognitive impairment remain largely unexplored. This study aimed to investigate potential associations between abnormal cerebellar functional connectivity (FC) and changes in cognitive function by examining intracerebellar and cerebellar-cerebral FC. METHODS: MRI data were collected from seventy-two patients with vascular mild cognitive impairment (VMCI), comprising 38 patients with small vessel mild cognitive impairment (SVMCI) and 34 with poststroke mild cognitive impairment (PSMCI), and from 43 demographically matched healthy controls (HCs). Changes in FC between subregions within the cerebellum and from each cerebellar subregion to the selected cerebral seed points in VMCI patients were calculated, and the association of these changes with cognitive function was examined. RESULTS: Compared with HCs, we found that VMCI patients had 11 cerebellar subregions showing significant differences (mainly decreases) in FC with brain regions in the default-mode network (DMN), sensory-motor network (SMN), and frontoparietal network (FPN). In the intracerebellar FC analysis, 47 (8%) cerebellar connections had significant intergroup differences, mainly a reduced magnitude of FC in VMCI patients. In the correlation analysis, higher Montreal Cognitive Assessment (MoCA) scores were correlated with stronger intracerebellar FC (left crus II-right lobule VI, left crus II-right lobule VIIb) and cerebellar-cerebral FC (right lobule X-left precuneus, vermal lobule IX-right inferior parietal lobule) in both the SVMCI and PSMCI groups. CONCLUSION: These findings suggest prominent intracerebellar and cerebellar-cerebral FC abnormalities in VMCI patients, contributing evidence for a possible role of the cerebellum in cognitive processes.


Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Humanos , Cerebelo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lobo Parietal , Disfunção Cognitiva/diagnóstico por imagem
9.
Front Neurol ; 13: 790607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185761

RESUMO

OBJECTIVE: The neuroimaging pattern in brain networks after articulation rehabilitation can be detected using graph theory and multivariate pattern analysis (MVPA). In this study, we hypothesized that the characteristics of the topology pattern of brain structural network in articulation-rehabilitated children with non-syndromic cleft lip and palate (NSCLP) were similar to that in healthy comparisons. METHODS: A total of 28 children with NSCLP and 28 controls with typical development were scanned for diffusion tensor imaging on a 3T MRI scanner. Structural networks were constructed, and their topological properties were obtained. Besides, the Chinese language clear degree scale (CLCDS) scores were used for correlation analysis with topological features in patients with NSCLP. RESULTS: The NSCLP group showed a similar rich-club connection pattern, but decreased small-world index, normalized rich-club coefficient, and increased connectivity strength of connections compared to controls. The univariate and multivariate patterns of the structural network in articulation-rehabilitated children were primarily in the feeder and local connections, covering sensorimotor, visual, frontoparietal, default mode, salience, and language networks, and orbitofrontal cortex. In addition, the connections that were significantly correlated with the CLCDS scores, as well as the weighted regions for classification, were chiefly distributed in the dorsal and ventral stream associated with the language networks of the non-dominant hemisphere. CONCLUSION: The average level rich-club connection pattern and the compensatory of the feeder and local connections mainly covering language networks may be related to the CLCDS in articulation-rehabilitated children with NSCLP. However, the patterns of small-world and rich-club structural organization in the articulation-rehabilitated children exhibited a random network and non-rich-club organization tendency. These findings enhanced the understanding of neuroimaging patterns in children with NSCLP after articulation rehabilitation.

10.
Front Neurol ; 13: 825177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812120

RESUMO

Objective: Even with successful combination antiretroviral therapy (cART), patients with human immunodeficiency virus positive (HIV+) continue to present structural alterations and neuropsychological impairments. The purpose of this study is to investigate structural brain connectivity alterations and identify the hub regions in HIV+ patients with fully suppressed plasma viral loads. Methods: In this study, we compared the brain structural connectivity in 48 patients with HIV+ treated with a combination of antiretroviral therapy and 48 healthy controls, using diffusion tensor imaging. Further comparisons were made in 24 patients with asymptomatic neurocognitive impairment (ANI) and 24 individuals with non-HIV-associated neurocognitive disorders forming a subset of HIV+ patients. The graph theory model was used to establish the topological metrics. Rich-club analysis was used to identify hub nodes across groups and abnormal rich-club connections. Correlations of connectivity metrics with cognitive performance and clinical variables were investigated as well. Results: At the regional level, HIV+ patients demonstrated lower degree centrality (DC), betweenness centrality (BC), and nodal efficiency (NE) at the occipital lobe and the limbic cortex; and increased BC and nodal cluster coefficient (NCC) in the occipital lobe, the frontal lobe, the insula, and the thalamus. The ANI group demonstrated a significant reduction in the DC, NCC, and NE in widespread brain regions encompassing the occipital lobe, the frontal lobe, the temporal pole, and the limbic system. These results did not survive the Bonferroni correction. HIV+ patients and the ANI group had similar hub nodes that were mainly located in the occipital lobe and subcortical regions. The abnormal connections were mainly located in the occipital lobe in the HIV+ group and in the parietal lobe in the ANI group. The BC in the calcarine fissure was positively correlated with complex motor skills. The disease course was negatively correlated with NE in the middle occipital gyrus. Conclusion: The results suggest that the occipital lobe and the subcortical regions may be important in structural connectivity alterations and cognitive impairment. Rich-club analysis may contribute to our understanding of the neuropathology of HIV-associated neurocognitive disorders.

11.
Front Pharmacol ; 13: 814623, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153786

RESUMO

Insomnia and anxiety are two common clinical diseases that threaten people's physical and mental health. Insomnia and anxiety may share some similar underlying neural circuit mechanisms in the brain. In this study, we combine techniques including chemo-fMRI, optogenetics, and chemogenetics to reveal that the glutamatergic neurons of the paraventricular hypothalamic nucleus (PVN) regulate both anxiety and arousal through two different downstream neural circuits. Optogenetic activation of the PVN-cingulate cortex (Cg) neural circuit triggers anxiety-like behaviors in mice without affecting the wakefulness, while optogenetic activation of the PVN-paraventricular thalamic nucleus (PVT) neural circuit promotes wakefulness in mice without affecting anxiety-like behaviors. Our research reveals that PVN is a key brain area for controlling anxiety and arousal behaviors. We also provide a neurological explanation for anxiety disorder and insomnia which may offer guidance for treatments including drugs or transcranial magnetic stimulation for the patients.

12.
Front Neurol ; 13: 869871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203980

RESUMO

Background: While regional brain structure and function alterations in HIV-infected individuals have been reported, knowledge about the topological organization in gray matter networks is limited. This research aims to investigate the effects of early HIV infection and combination antiretroviral therapy (cART) on gray matter structural covariance networks (SCNs) by employing graph theoretical analysis. Methods: Sixty-five adult HIV+ individuals (25-50 years old), including 34 with cART (HIV+/cART+) and 31 medication-naïve (HIV+/cART-), and 35 demographically matched healthy controls (HCs) underwent high-resolution T1-weighted images. A sliding-window method was employed to create "age bins," and SCNs (based on cortical thickness) were constructed for each bin by calculating Pearson's correlation coefficients. The group differences of network indices, including the mean nodal path length (Nlp), betweenness centrality (Bc), number of modules, modularity, global efficiency, local efficiency, and small-worldness, were evaluated by ANOVA and post-hoc tests employing the network-based statistics method. Results: Relative to HCs, less efficiency in terms of information transfer in the parietal and occipital lobe (decreased Bc) and a compensated increase in the frontal lobe (decreased Nlp) were exhibited in both HIV+/cART+ and HIV+/cART- individuals (P < 0.05, FDR-corrected). Compared with HIV+/cART- and HCs, less specialized function segregation (decreased modularity and small-worldness property) and stronger integration in the network (increased Eglob and little changed path length) were found in HIV+/cART+ group (P < 0.05, FDR-corrected). Conclusion: Early HIV+ individuals exhibited a decrease in the efficiency of information transmission in sensory regions and a compensatory increase in the frontal lobe. HIV+/cART+ showed a less specialized regional segregation function, but a stronger global integration function in the network.

13.
Front Neurol ; 13: 996459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203989

RESUMO

Objective: Even after palatoplasty and speech rehabilitation, patients with cleft lip and palate (CLP) remain to produce pronunciation errors. We hypothesized that nonsyndromic CLP (NSCLP) after speech rehabilitation had structural abnormalities in language-related brain regions. This study investigates structural patterns in NSCLP children after speech rehabilitation using surface-based morphometry (SBM) analysis. Methods: Forty-two children with NSCLP and 42 age- and gender-matched healthy controls were scanned for 3D T1-weighted images on a 3T MRI scanner. After reconstructing each brain surface, we computed SBM parameters and assessed between-group differences using two-sample t-tests and permutation tests (5,000 times). Then, we assessed the relationship between the SBM parameters and the Chinese language clear degree scale (CLCDS) using Pearson's correlation analysis. Result: The speech-rehabilitated children with NSCLP showed lower cortical thickness and higher gyrification index mainly involving left language-related brain regions (permutation tests, p < 0.05). Furthermore, the lower cortical thickness of the left parahippocampal gyrus was positively correlated with CLCDS scores (r = 0.370, p = 0.017) in patients with NSCLP. Conclusion: The SBM analysis showed that the structural abnormalities of speech-rehabilitated children with NSCLP mainly involved language-related brain regions, especially the dominant cerebral hemisphere. The structural abnormalities of the cortical thickness and folding in the language-related brain regions might be the neural mechanisms of speech errors in NSCLP children after speech rehabilitation. The cortical thickness of the parahippocampal gyrus may be a biomarker to evaluate pronunciation function.

14.
Acta Biomater ; 153: 431-441, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36174937

RESUMO

Photodynamic therapy (PDT) has become a promising cancer treatment due to in situ generation of cytotoxic reactive oxygen (ROS); however, it remains limited by the hypoxia of tumor microenvironment (TME) and penetration depth of laser. Herein, we developed a kind of GSH-/H2O2-responsive copper-encapsulating magnetic nanoassemblies (MNSs) for switchable T1-weighted magnetic resonance imaging (MRI) and enzyme-like activity potentiating PDT of cancer. MNSs were rationally constructed using the chelation effect of copper ions (Cu2+) with polyacrylic acid-coated ultrasmall iron oxide nanoparticles (UIONPs). After uptake by tumor cells, the incorporated Cu2+ of MNSs was reduced to Cu+ through the intracellular GSH, which resulted in the disassembly of MNSs accompanied by the "silenced" MR signal shifting to a positive state. Sequentially, the generated Cu+ manifested peroxidase-like activity, catalyzing local H2O2 in TME to cytotoxic ·OH for chemodynamic therapy. Furthermore, Cu2+ and UIONPs could decompose H2O2 to O2, thus providing extra oxygen necessary for enhancing the PDT effect of photosensitizer IR-780. Finally, IR-780-loading MNSs (MNSs@IR-780) under laser irradiation significantly inhibited tumor growth and prolonged the survival of gastric MGC-803 tumor-bearing mice. Therefore, this study provides a versatile nanoplatform as a tumor-responsive theragnostic agent. STATEMENT OF SIGNIFICANCE: Tumor hypoxia and penetration depth of laser severely hindered the PDT of cancer. Valence-convertible metal ions (VCMI, e.g., Cu2+/Cu+, Fe3+/Fe2+) have been reported as Fenton-like agents disintegrating H2O2 to O2 to enhance PDT. Tumor-delivery of VCMI is of essential importance for in situ triggering of a Fenton-like reaction. We thereby developed magnetic nanoassemblies (MNSs) to encapsulate Cu2+ and load photosensitizer (IR-780). Stimulated by GSH and H2O2, MNSs performed catalase/peroxidase-like activity that provided extra O2 for PDT and catalyzed H2O2 to ·OH for CDT. Consequently, IR-780-loading MNSs under laser irradiation significantly inhibit the tumor growth due to effective tumor delivery of Cu2+ and IR-780. This study might offer a feasible nanoplatform for tumor-delivery of metal ions and drugs.


Assuntos
Antineoplásicos , Neoplasias , Fotoquimioterapia , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Cobre/farmacologia , Peróxido de Hidrogênio/farmacologia , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Microambiente Tumoral , Antineoplásicos/farmacologia , Neoplasias/patologia , Imageamento por Ressonância Magnética , Oxigênio/farmacologia , Peroxidases/farmacologia , Peroxidases/uso terapêutico
15.
Front Aging Neurosci ; 14: 893297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003999

RESUMO

Background: Neural reorganization occurs after a stroke, and dynamic functional network connectivity (dFNC) pattern is associated with cognition. We hypothesized that dFNC alterations resulted from neural reorganization in post-stroke cognitive impairment (PSCI) patients, and specific dFNC patterns characterized different pathological types of PSCI. Methods: Resting-state fMRI data were collected from 16 PSCI patients with hemorrhagic stroke (hPSCI group), 21 PSCI patients with ischemic stroke (iPSCI group), and 21 healthy controls (HC). We performed the dFNC analysis for the dynamic connectivity states, together with their topological and temporal features. Results: We identified 10 resting-state networks (RSNs), and the dFNCs could be clustered into four reoccurring states (modular, regional, sparse, and strong). Compared with HC, the hPSCI and iPSCI patients showed lower standard deviation (SD) and coefficient of variation (CV) in the regional and modular states, respectively (p < 0.05). Reduced connectivities within the primary network (visual, auditory, and sensorimotor networks) and between the primary and high-order cognitive control domains were observed (p < 0.01). Conclusion: The transition trend to suboptimal states may play a compensatory role in patients with PSCI through redundancy networks. The reduced exploratory capacity (SD and CV) in different suboptimal states characterized cognitive impairment and pathological types of PSCI. The functional disconnection between the primary and high-order cognitive control network and the frontoparietal network centered (FPN-centered) incomplete compensation may be the pathological mechanism of PSCI. These results emphasize the flexibility of neural reorganization during self-repair.

16.
Brain Imaging Behav ; 16(6): 2608-2617, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36136202

RESUMO

The topology of brain networks is the foundation of cognition. We hypothesized that stroke damaged topological organization resulting in cognitive impairment. The aim was to explore the damage pattern of the resting-state topology in post-stroke cognitive impairment (PSCI) patients. Thirty-seven patients with PSCI and thirty-seven gender- and age-matched healthy controls (HC) were recruited. The structural and functional data were collected from all subjects. The degree centrality (DC), betweenness centrality (BC), and global properties of brain networks were analyzed between groups. Spearman correlation analysis was performed between topological properties that changed significantly and clinical cognitive function scale scores. Compared with HC, the PSCI patients had significantly reduced DC in language-related brain regions and significantly higher DC in the right frontal lobe, hippocampus, and paracentral lobule. The decreased BC was located in the left caudate, thalamus, temporal, and frontal lobes. The increased BC was detected in the left cuneus and right precuneus. In addition, PSCI exhibited increased characteristic path length and decreased small-worldness. PSCI patients had impaired functional topology of the language-related brain regions, mainly in the left hemisphere. The enhanced processing and relaying information of some right high-order cognitive brain regions may be a compensatory mechanism. However, the whole brain's function integration was reduced, and there was an imbalance between efficiency and consumption.


Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Imageamento por Ressonância Magnética/métodos , Idioma , Encéfalo/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Mapeamento Encefálico/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia
17.
Brain Behav ; 11(8): e02094, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34343416

RESUMO

INTRODUCTION: Speech therapy is the primary management followed the physical management through surgery for children with nonsyndromic cleft lip and palate (NSCLP). However, the topological pattern of the resting-state network after rehabilitation remains poorly understood. We aimed to explore the functional topological pattern of children with NSCLP after speech rehabilitation compared with healthy controls. METHODS: We examined 28 children with NSCLP after speech rehabilitation (age = 10.0 ± 2.3 years) and 28 healthy controls for resting-state functional MRI. We calculated functional connections and the degree strength, betweenness centrality, network clustering coefficient (Cp), characteristic path length (Lp), global network efficiency (Eg), local network efficiency (Eloc), modularity index (Q), module number, and participation coefficient for the between-group differences using two-sample t tests (corrected p < .05). Additionally, we performed a correlation analysis between the Chinese language clear degree scale (CLCDS) scores and topological properties in children with NSCLP. RESULTS: We detected significant between-group differences in the areas under the curve (AUCs) of degree strength and betweenness centrality in language-related brain regions. There were no significant between-group differences in module number, participation coefficient, Cp, Lp, Eg, or Eloc. However, the Q (density: 0.05-0.30) and QAUC (t = 2.46, p = .02) showed significant between-group differences. Additionally, there was no significant correlation between topological properties of statistical between-group differences and CLCDS scores. CONCLUSIONS: Although nodal metric differences existed in the language-related brain regions, the children with NSCLP after speech rehabilitation had similar global network properties, module numbers, and participation coefficient, but increased modularity. Our results suggested that children with NSCLP achieved speech rehabilitation through function specialization in the language-related brain regions. The resting-state topology pattern could be of substantive neurobiological importance and potential imaging biomarkers for speech rehabilitation.


Assuntos
Fenda Labial , Fissura Palatina , Criança , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Humanos , Fala , Fonoterapia
18.
Rev Sci Instrum ; 92(2): 023508, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648125

RESUMO

Dispersion interferometry (DI) is a promising method for density measurement. Compared with the traditional interferometer, the DI is immune to mechanical vibration and can avoid the fringe jump error. In addition, a simple optical configuration is also one of the advantages of the DI. The electron density of the Huazhong University of Science and Technology field-reversed configuration (HFRC) device can reach 1020 m-3 with a pulse length of 50 µs. In this case, the DI based on the CO2 laser on the HFRC device adopts the heterodyne technique based on the acousto-optic modulator, which can increase the temporal resolution to 40 MHz. It can realize density fluctuation measurements in the MHz range. The test of each optical element, especially the nonlinear crystal, has been completed. The AgGaSe2 crystal can produce a second harmonic wave of about 52.5 µW when the incident CO2 power is 10 W. Based on these designs and tests, a DI system can be expected on the HFRC device.

19.
Front Aging Neurosci ; 13: 724267, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483891

RESUMO

Stroke causes alterations in local spontaneous neuronal activity and related networks functional connectivity. We hypothesized that these changes occur in patients with post-stroke cognitive impairment (PSCI). Fractional amplitude of low-frequency fluctuations (fALFF) was calculated in 36 patients with cognitive impairment, including 16 patients with hemorrhagic stroke (hPSCI group), 20 patients with ischemic stroke (iPSCI group). Twenty healthy volunteers closely matched to the patient groups with respect to age and gender were selected as the healthy control group (HC group). Regions with significant alteration were regarded as regions of interest (ROIs) using the one-way analysis of variance, and then the seed-based functional connectivity (FC) with other regions in the brain was analyzed. Pearson correlation analyses were performed to investigate the correlation between functional indexes and cognitive performance in patients with PSCI. Our results showed that fALFF values of bilateral posterior cingulate cortex (PCC)/precuneus and bilateral anterior cingulate cortex in the hPSCI group were lower than those in the HC group. Compared with the HC group, fALFF values were lower in the superior frontal gyrus and basal ganglia in the iPSCI group. Correlation analysis showed that the fALFF value of left PCC was positively correlated with MMSE scores and MoCA scores in hPSCI. Besides, the reduction of seed-based FC values was reported, especially in regions of the default-mode network (DMN) and the salience network (SN). Abnormalities of spontaneous brain activity and functional connectivity are observed in PSCI patients. The decreased fALFF and FC values in DMN of patients with hemorrhagic and SN of patients with ischemic stroke may be the pathological mechanism of cognitive impairment. Besides, we showed how to use fALFF values and functional connectivity maps to specify a target map on the cortical surface for repetitive transcranial magnetic stimulation (rTMS).

20.
Rev Sci Instrum ; 92(10): 103504, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717408

RESUMO

As one of the most important diagnostics of field reversed plasma, the single-flux loop around the vacuum chamber is usually used to measure the magnetic flux to deduce the plasma size. In the theta-pinch process, the power supply will drive a large current through the coil in a short time to generate a high magnetic field, which will cause the magnetic flux in the vacuum chamber to rise sharply. Therefore, the induced voltage on the single-flux loop may be very strong and have high-frequency components. A voltage divider must be used to reduce the induced voltage to the range that the transmission line can withstand. According to the high-frequency characteristics of the measured signal, this paper designs a capacitor voltage divider single-flux loop with reference to the capacitive voltage divider in the industry. After theoretical derivation of parameter selection and then in the preliminary experimental test with and without plasma, the effectiveness of the distributed capacitor flux loop is verified.

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