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Morphological features sourced from structural magnetic resonance imaging can be used to infer human brain connectivity. Although integrating different morphological features may theoretically be beneficial for obtaining more precise morphological connectivity networks (MCNs), the empirical evidence to support this supposition is scarce. Moreover, the incorporation of different morphological features remains an open question. In this study, we proposed a method to construct cortical MCNs based on multiple morphological features. Specifically, we adopted a multi-dimensional kernel density estimation algorithm to fit regional joint probability distributions (PDs) from different combinations of four morphological features, and estimated inter-regional similarity in the joint PDs via Jensen-Shannon divergence. We evaluated the method by comparing the resultant MCNs with those built based on different single morphological features in terms of topological organization, test-retest reliability, biological plausibility, and behavioral and cognitive relevance. We found that, compared to MCNs built based on different single morphological features, MCNs derived from multiple morphological features displayed less segregated, but more integrated network architecture and different hubs, had higher test-retest reliability, encompassed larger proportions of inter-hemispheric edges and edges between brain regions within the same cytoarchitectonic class, and explained more inter-individual variance in behavior and cognition. These findings were largely reproducible when different brain atlases were used for cortical parcellation. Further analysis of macaque MCNs revealed weak, but significant correlations with axonal connectivity from tract-tracing, independent of the number of morphological features. Altogether, this paper proposes a new method for integrating different morphological features, which will be beneficial for constructing MCNs.
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Córtex Cerebral , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/anatomia & histologia , Adulto , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/anatomia & histologia , Conectoma/métodos , Algoritmos , Adulto Jovem , Processamento de Imagem Assistida por Computador/métodos , Mapeamento Encefálico/métodosRESUMO
Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.
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Circulação Cerebrovascular , Microbioma Gastrointestinal , Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono , Transcriptoma , Humanos , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , FenótipoRESUMO
Despite the prevalence of research on single-subject cerebral morphological networks in recent years, whether they can offer a reliable way for multicentric studies remains largely unknown. Using two multicentric datasets of traveling subjects, this work systematically examined the inter-site test-retest (TRT) reliabilities of single-subject cerebral morphological networks, and further evaluated the effects of several key factors. We found that most graph-based network measures exhibited fair to excellent reliabilities regardless of different analytical pipelines. Nevertheless, the reliabilities were affected by choices of morphological index (fractal dimension > sulcal depth > gyrification index > cortical thickness), brain parcellation (high-resolution > low-resolution), thresholding method (proportional > absolute), and network type (binarized > weighted). For the factor of similarity measure, its effects depended on the thresholding method used (absolute: Kullback-Leibler divergence > Jensen-Shannon divergence; proportional: Jensen-Shannon divergence > Kullback-Leibler divergence). Furthermore, longer data acquisition intervals and different scanner software versions significantly reduced the reliabilities. Finally, we showed that inter-site reliabilities were significantly lower than intra-site reliabilities for single-subject cerebral morphological networks. Altogether, our findings propose single-subject cerebral morphological networks as a promising approach for multicentric human connectome studies, and offer recommendations on how to determine analytical pipelines and scanning protocols for obtaining reliable results.
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Conectoma , Imageamento por Ressonância Magnética , Humanos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/anatomia & histologia , Conectoma/métodosRESUMO
BACKGROUND: The Maillard reaction involves the interaction of various amino acids and reducing sugars, resulting in food browning. It often produces appealing aromas and flavors. The complexities of the reaction are such that it can be challenging to identify the often numerous and frequently volatile products formed by it. In the present study, we sought to identify and evaluate an unusual product with anti-oxidant activity arising from a fructose-histidine Maillard reaction model. The anti-oxidant profile of this product was assessed by computational means. RESULTS: The fructose-histidine Maillard reaction products (FH-MRPs) were generated by heating a 2:1 mixture of the sugar and the amino acid at 140 °C for 2 h. Chromatographically separable fractions, labelled DM-1 to DM-8, were obtained using silica gel as the stationary phase and dichloromethane/methanol (DCM/MeOH) mixtures as the mobile one. Fraction DM-5 exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and further bio-assay guided fractionation led to isolation and identification of 1-(1H-imidazo[4,5-c]pyridin-4-yl)ethenone (IMPE) as the active principal, the structure of which was established by nuclear magnetic resonance (NMR) spectroscopic and mass spectral techniques. A mechanism for the formation of IMPE from its precursors is proposed. Density functional theory (DFT) calculations suggest this novel heterocyclic compound exerts its anti-oxidant effects by interacting with DPPH and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Essentially, IMPE was non-toxic below 300 ug mL-1, showing a concentration-dependent free radical clearance capacity and reducing power within the 100-1000 µg mL-1 range, and moreover, exhibiting significant Fe2+ chelating abilities wihin the 50-200 µg mL-1 range. CONCLUSION: This study identified the unique FH-MRP, IMPE, and found that it acts as food antioxidant through the chelation of metal ions. © 2024 Society of Chemical Industry.
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BACKGROUND: Major depressive disorder (MDD) is associated with widespread, irregular cortical thickness (CT) reductions across the brain. However, little is known regarding mechanisms that govern spatial distribution of the reductions. METHODS: We combined multimodal MRI and genetic, cytoarchitectonic and chemoarchitectonic data to examine structural covariance, functional synchronization, gene co-expression, cytoarchitectonic similarity and chemoarchitectonic covariance between regions atrophied in MDD. RESULTS: Regions atrophied in MDD were associated with significantly higher structural covariance, functional synchronization, gene co-expression and chemoarchitectonic covariance. These results were robust against methodological variations in brain parcellation and null model, reproducible in patients and controls, and independent of age at onset of MDD. Despite no significant differences in the cytoarchitectonic similarity, MDD-related CT reductions were susceptible to specific cytoarchitectonic class of association cortex. Further, we found that nodal shortest path lengths to disease epicenters derived from structural (right supramarginal gyrus) and chemoarchitectonic covariance (right sulcus intermedius primus) networks of healthy brains were correlated with the extent to which a region was atrophied in MDD, supporting the transneuronal spread hypothesis that regions closer to the epicenters are more susceptible to MDD. Finally, we showed that structural covariance and functional synchronization among regions atrophied in MDD were mainly related to genes enriched in metabolic and membrane-related processes, driven by genes in excitatory neurons, and associated with specific neurotransmitter transporters and receptors. CONCLUSIONS: Altogether, our findings provide empirical evidence for and genetic and molecular insights into connectivity-constrained CT thinning in MDD.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Afinamento Cortical Cerebral , Encéfalo , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Although single-subject morphological brain networks provide an important way for human connectome studies, their roles and origins are poorly understood. Combining cross-sectional and repeated structural magnetic resonance imaging scans from adults, children and twins with behavioral and cognitive measures and brain-wide transcriptomic, cytoarchitectonic and chemoarchitectonic data, this study examined phenotypic associations and neurobiological substrates of single-subject morphological brain networks. We found that single-subject morphological brain networks explained inter-individual variance and predicted individual outcomes in Motor and Cognition domains, and distinguished individuals from each other. The performance can be further improved by integrating different morphological indices for network construction. Low-moderate heritability was observed for single-subject morphological brain networks with the highest heritability for sulcal depth-derived networks and higher heritability for inter-module connections. Furthermore, differential roles of genetic, cytoarchitectonic and chemoarchitectonic factors were observed for single-subject morphological brain networks. Cortical thickness-derived networks were related to the three factors with contributions from genes enriched in membrane and transport related functions, genes preferentially located in supragranular and granular layers, overall thickness in the molecular layer and thickness of wall in the infragranular layers, and metabotropic glutamate receptor 5 and dopamine transporter; fractal dimension-, gyrification index- and sulcal depth-derived networks were only associated with the chemoarchitectonic factor with contributions from different sets of neurotransmitter receptors. Most results were reproducible across different parcellation schemes and datasets. Altogether, this study demonstrates phenotypic associations and neurobiological substrates of single-subject morphological brain networks, which provide intermediate endophenotypes to link molecular and cellular architecture and behavior and cognition.
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Córtex Cerebral , Conectoma , Adulto , Criança , Humanos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/anatomia & histologia , Estudos Transversais , Encéfalo/anatomia & histologia , Cognição , Imageamento por Ressonância Magnética/métodos , Conectoma/métodosRESUMO
Age-related changes in focal cortical morphology have been well documented in previous literature; however, how interregional coordination patterns of the focal cortical morphology reorganize with advancing age is not well established. In this study, we performed a comprehensive analysis of the topological changes in single-subject morphological brain networks across the adult lifespan. Specifically, we constructed four types of single-subject morphological brain networks for 650 participants (aged from 18 to 88 years old), and characterized their topological organization using graph-based network measures. Age-related changes in the network measures were examined via linear, quadratic, and cubic models. We found profound age-related changes in global small-world attributes and efficiency, local nodal centralities, and interregional similarities of the single-subject morphological brain networks. The age-related changes were mainly embodied in cortical thickness networks, involved in frontal regions and highly connected hubs, concentrated on short-range connections, characterized by linear changes, and susceptible to connections between limbic, frontoparietal, and ventral attention networks. Intriguingly, nonlinear (i.e., quadratic or cubic) age-related changes were frequently found in the insula and limbic regions, and age-related cubic changes preferred long-range morphological connections. Finally, we demonstrated that the morphological similarity in cortical thickness between two frontal regions mediated the relationship between age and cognition measured by Cattell scores. Taken together, these findings deepen our understanding of adaptive changes of the human brain with advancing age, which may account for interindividual variations in behaviors and cognition.
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Longevidade , Imageamento por Ressonância Magnética , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Mapeamento Encefálico , CogniçãoRESUMO
BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.
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Conectoma , Esclerose Múltipla , Neuromielite Óptica , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/genética , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/genética , Neuromielite Óptica/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética , Cerebelo/diagnóstico por imagem , Cerebelo/patologiaRESUMO
Chitosan (CS) based nanoparticles (NPs) were fabricated via an ionic gelation reaction modified by flaxseed gum (FG) or sodium tripolyphosphate (STPP). The average particle size, morphology, interfacial tension, and wettability of NPs were characterized. The particle size of CS-STPP-HA (hyaluronic acid)-FA (ferulic acid) NPs and CS-FG-HA-FA NPs was 400.8 nm and 262.4 nm, respectively under the optimized conditions of CS/STPP = 5:1 (w/w) or CS/FG = 1:1 (v/v) with HA concentration of 0.25 mg/mL and FA dosage of 25 µM. FG acted as a good alternative for STPP to form particles with CS in stabilizing Pickering emulsion with an internal diacylglycerol (DAG) phase of 50-80 % (v/v). The complex nanoparticles had high surface activity and contact angle close to 90 °C, being able to tightly packed at the droplet surface. The emulsions had high thermal, ionic and oxidative stability. With the aid of moisturizing polysaccharides and DAG oil, the emulsions had a good sustained-release ability for FA with deeper penetration and retention into the dermis of the skin. Thus, FG and HA-based NPs serve as green vehicles for the fabrication of novel Pickering emulsions and possess great potential to be applied as a delivery system for lipophilic active agents in functional food and cosmetic products.
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Quitosana , Linho , Nanopartículas , Ácido Hialurônico , Emulsões , Tamanho da PartículaRESUMO
This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.
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Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good-to-excellent test-retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co-expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co-expression, and is associated with serotonergic system-related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease.
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Alzheimer's disease (AD) has a complex pathogenesis, and multiple studies have indicated that histone post-translational modifications, especially acetylation, play a significant role in it. With the development of mass spectrometry and proteomics, an increasing number of novel HPTMs, including lactoylation, crotonylation, ß-hydroxybutyrylation, 2-hydroxyisobutyrylation, succinylation, and malonylation, have been identified. These novel HPTMs closely link substance metabolism to gene regulation, and an increasing number of relevant studies on the relationship between novel HPTMs and AD have become available. This review summarizes the current advances and implications of novel HPTMs in AD, providing insight into the deeper pathogenesis of AD and the development of novel drugs.
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Doença de Alzheimer , Histonas , Humanos , Histonas/metabolismo , Doença de Alzheimer/genética , Metilação de DNA , Processamento de Proteína Pós-Traducional , AcetilaçãoRESUMO
BACKGROUND: Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking. METHODS: We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments. Individual hearing abilities indexed by pure tone average (PTA) were correlated with multiple structural MRI-derived cortical morphological indices. For regions showing significant correlations, mediation analyses were performed to examine their role in the relationship between hearing ability and cognitive function. Finally, the correlation maps between hearing ability and cortical morphology were linked with publicly available connectomic gradient, transcriptomic, and neurotransmitter maps. FINDINGS: Poorer hearing was related to cortical thickness (CT) reductions in widespread regions and gyrification index (GI) reductions in the right Area 52 and Insular Granular Complex. The GI in the right Area 52 mediated the relationship between hearing ability and executive function. This mediating effect was further modulated by glutamate and N-acetylaspartate levels in the right auditory region. The PTA-CT correlation map followed microstructural connectomic hierarchy, were related to genes involved in certain biological processes (e.g., glutamate metabolic process), cell types (e.g., excitatory neurons and astrocytes), and developmental stages (i.e., childhood to young adulthood), and covaried with dopamine receptor 1, dopamine transporter, and fluorodopa. The PTA-GI correlation map was related to 5-hydroxytryptamine receptor 2a. INTERPRETATION: Poorer hearing is associated with cortical thinning and folding reductions, which may be engaged in the relationship between hearing impairment and cognitive decline in the elderly and have different neurobiological substrates. FUNDING: See the Acknowledgements section.
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Córtex Cerebral , Cognição , Imageamento por Ressonância Magnética , Humanos , Idoso , Masculino , Feminino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Audição , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Perda Auditiva/etiologia , Conectoma , Pessoa de Meia-Idade , Mapeamento Encefálico , Idoso de 80 Anos ou maisRESUMO
Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.
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Óleo de Semente do Linho , Triptofano , gama-Tocoferol , Triptofano/química , Óleo de Semente do Linho/química , gama-Tocoferol/química , Oxirredução , Antioxidantes/química , Espectrometria de Massas em Tandem , Linho/químicaRESUMO
Linusorbs (LO), cyclolinopeptides, are a group of cyclic hydrophobic peptides and considered a valuable by-product of flaxseed oil due to numerous health benefits. Currently applied acetone or methanol extraction could contaminate the feedstocks for further food-grade application. Using flaxseed cake as feedstock, this study established a practical method for preparing LO from pressed cake. Firstly, LO composition of 15 flaxseed cultivars was analyzed. Next, cold-pressed cake was milled and screened mechanically. The kernel and hull fractions were separated based on the disparity of their mechanical strength. Monitored by hyperspectral fluorescence, the LO-enriched kernel fraction separated from cold-pressed flaxseed cake was further used as feedstock for LO production. After ethanol extraction, partition, and precipitation, LOs were extracted from cold-pressed flaxseed cake with a purity of 91.4%. The proposed method could serve as feasible flaxseed cake valorization strategy and enable the preparation of other polar compounds such as flax lignan and mucilage.
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Linho , Peptídeos Cíclicos , Sementes , Linho/química , Sementes/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/análise , Manipulação de Alimentos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Background: Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain networks. However, the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD. Objective: To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD. Methods: Twenty-five first-episode, treatment-naive adolescents with MDD and 19 healthy controls (HCs) underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests. Single-subject morphological brain networks were constructed separately based on cortical thickness, fractal dimension, gyrification index, and sulcus depth, and topologically characterized by graph-based approaches. Between-group differences were inferred by permutation testing. For significant alterations, partial correlations were used to examine their associations with clinical and neuropsychological variables in the patients. Finally, a support vector machine was used to classify the patients from controls. Results: Compared with the HCs, the patients exhibited topological alterations only in cortical thickness-based networks characterized by higher nodal centralities in parietal (left primary sensory cortex) but lower nodal centralities in temporal (left parabelt complex, right perirhinal ectorhinal cortex, right area PHT and right ventral visual complex) regions. Moreover, decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients. These results were largely reproducible for binary and weighted network analyses. Finally, topological properties of the cortical thickness-based networks were able to distinguish the MDD adolescents from HCs with 87.6% accuracy. Conclusion: Adolescent MDD is associated with disrupted topological organization of morphological brain networks, and the disruptions provide potential biomarkers for diagnosing and monitoring the disease.
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It has been well established that very-high-altitude (>4000 m) environments can affect human cognitive function and brain activity. However, the effects of long-term exposure to moderate altitudes (2000−3000 m) on cognitive function and brain activity are not well understood. In the present cross-sectional study, we utilized an N-back working memory task and resting-state functional near-infrared spectroscopy to examine the effects of two years of exposure to 2260 m altitude on working memory and resting-state brain activity in 208 college students, compared with a control group at the sea level. The results showed that there was no significant change in spatial working memory performance after two years of exposure to 2260 m altitude. In contrast, the analysis of resting-state brain activity revealed changes in functional connectivity patterns in the prefrontal cortex (PFC), with the global efficiency increased and the local efficiency decreased after two years of exposure to 2260 m altitude. These results suggest that long-term exposure to moderate altitudes has no observable effect on spatial working memory performance, while significant changes in functional connectivity and brain network properties could possibly occur to compensate for the effects of mild hypoxic environments. To our knowledge, this study is the first to examine the resting state activity in the PFC associated with working memory in people exposed to moderate altitudes.
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Introduction: Both major depressive disorder (MDD) and schizophrenia (SCH) are characterized by neurodevelopmental abnormalities; however, transdiagnostic and diagnosis-specific patterns of such abnormalities have rarely been examined, particularly in large-scale functional brain networks via advanced multilayer network models. Methods: Here, we collected resting-state functional magnetic resonance imaging data from 45 MDD patients, 64 SCH patients, and 48 healthy controls (HCs; 13-45 years old), and we constructed functional networks in different frequency intervals. The frequency-dependent networks were then fused by multiplex network models, followed by graph-based topological analyses. Results: We found that functional networks of the patients showed common neurodevelopmental abnormalities in the right ventromedial parietooccipital sulcus (opposite correlations with age to HCs), whereas functional networks of the MDD patients exhibited specific alterations in the left superior parietal lobule and right precentral gyrus with respect to cross-frequency interactions. These findings were quite different from those from brain networks within each frequency interval, which revealed SCH-specific neurodevelopmental abnormalities in the right superior temporal gyrus (opposite correlations with age to the other two groups) in 0.027-0.073 Hz, and SCH-specific alterations in the left superior temporal gyrus and bilateral insula in 0.073-0.198 Hz. Finally, multivariate analysis of age prediction revealed that the subcortical network lost prediction ability in both patient groups, whereas the visual network exhibited additional prediction ability in the MDD patients. Discussion and Conclusion: Altogether, these findings demonstrate transdiagnostic and diagnosis-specific neurodevelopmental abnormalities and alterations in large-scale functional brain networks between MDD and SCH, which have important implications for understanding shared and unique neural mechanisms underlying the diseases.
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Conectoma , Transtorno Depressivo Maior , Esquizofrenia , Adolescente , Adulto , Encéfalo , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Despite accumulating evidence for the hippocampus as a key dysfunctional node in major depressive disorder (MDD), previous findings are controversial possibly due to heterogeneous and small clinical samples, complicated hippocampal structure, and different imaging modalities and analytical methods. METHODS: We collected structural and resting-state functional MRI data from 100 first-episode, drug-naïve MDD patients and 99 healthy controls. A subset of the participants (34 patients and 33 controls) also completed a battery of neuropsychological tests and childhood trauma questionnaires. Seed-based morphological and functional (static and dynamic) connectivity were calculated for ten hippocampal subregions, followed by analyses of dynamic functional connectivity states (k-means clustering), connectivity cross-modality relationships (cosine similarity), and connectivity associations with clinical and neuropsychological variables (Spearman correlation). RESULTS: Between-group comparisons revealed abnormal hippocampal connectivity in the patients that depended on 1) hippocampal subdivisions: the cornu ammonis (CA) was the most seriously affected subregion, in particular the right CA1 for functional connectivity alterations; 2) imaging modality: morphological connectivity revealed seldom and sporadic alterations with different lobes, while functional connectivity identified numerous and convergent alterations with prefrontal regions; and 3) time scale: dynamic functional connectivity was more sensitive than static functional connectivity, in particular in revealing alterations between the right CA1 and contralateral prefrontal cortex. Among the 34 patients, functional connectivity alterations of the CA1 were related to the history of childhood trauma in the patients. LIMITATIONS: Only a subset of the patients completed the neuropsychological tests, which may cause underestimation of cognitive relevance of hippocampal connectivity alterations. CONCLUSIONS: Disrupted hippocampal CA1 functional connectivity plays key roles in the pathophysiology of MDD and may act as a potential diagnostic biomarker for the disease.
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Transtorno Depressivo Maior , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
The blue sheep is an endemic species to the Qinghai-Tibet Plateau and surrounding regions. It has been regarded as having 2 subspecies: Pseudois nayaur nayaur and P. n. szechuanensis. However, such a classification remains controversial. Herein, we analyze 10 microsatellite loci and part of the mitochondrial control region for clarification in such taxonomic debates. We use samples from 168 individuals from 6 geographic populations covering almost all the distribution areas of the species in China to carry out comparisons. Phylogenetic trees derived from both the microsatellite and mitochondrial markers combined with the discriminant analysis of principal components (DAPC) and the STRUCTURE analysis reveal that the individuals in the Helan Mountains are well grouped with a distinct evolutionary lineage and are significantly different from the other populations of P. n. szechuanensis according to Fst values, implying that this isolated population should be categorized as a valid subspecies; namely, Pseudois nayaur alashanicus. The isolation-by-distance (IBD) analysis shows a significant positive relationship between genetic and geographical distances among the populations.