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This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.
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Infartos do Tronco Encefálico , Cerebelo , Imageamento por Ressonância Magnética , Vias Neurais , Ponte , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Ponte/diagnóstico por imagem , Ponte/fisiopatologia , Infartos do Tronco Encefálico/fisiopatologia , Infartos do Tronco Encefálico/diagnóstico por imagem , Idoso , Adulto , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagemRESUMO
Nanoscale spatially controlled modulation of the properties of ferroelectrics via artificial domain pattering is crucial to their emerging optoelectronics applications. New patterning strategies to achieve high precision and efficiency and to link the resultant domain structures with device functionalities are being sought. Here, we present an epitaxial heterostructure of SrRuO3/PbTiO3/SrRuO3, wherein the domain configuration is delicately determined by the charge screening conditions in the SrRuO3 layer and the substrate strains. Chemical etching of the top SrRuO3 layer leads to a transition from in-plane a domains to out-of-plane c domains, accompanied by a giant (>105) modification in the second harmonic generation response. The modulation effect, coupled with the plasmonic resonance effect from SrRuO3, enables a highly flexible design of nonlinear optical devices, as demonstrated by a simulated split-ring resonator metasurface. This domain patterning strategy may be extended to more thin-film ferroelectric systems with domain stabilities amenable to electrostatic boundary conditions.
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Glomalin-related soil protein (GRSP) is a significant component in the sequestration of heavy metal in soils, but its mechanisms for metal adsorption are poorly known. This study combined spectroscopic data with molecular docking simulations to reveal metal adsorption onto GRSP's surface functional groups at the molecular level. The EXAFS combined with FTIR and XPS analyses indicated that the adsorption of Cd(II), Sr(II), and Ni(II) by GRSP occurred mainly through the coordination of -OH and -COOH groups with the metal. The -COOH and -OH groups bound to the metal as electron donors and the electron density of the oxygen atom decreased, suggesting that electrostatic attraction might be involved in the adsorption process. Two-dimensional correlation spectroscopy revealed that preferential adsorption occurred on GRSP for the metal in sequential order of -COOH groups followed by -OH groups. The presence of the Ni-C shell in the Ni EXAFS spectrum suggested that Ni formed organometallic complexes with the GRSP surface. However, Sr-C and Cd-C were absent in the second shell of the Sr and Cd spectra, which was attributed to the adsorption of Sr and Cd ions with large hydration ion radius by GRSP to form outer-sphere complexes. Through molecular docking simulations, negatively charged residues such as ASP151 and ASP472 in GRSP were found to provide electrostatic attraction and ligand combination for the metal adsorption, which was consistent with the spectroscopic analyses. Overall, these findings provided new insights into the interaction mechanisms between GRSP and metals, which will help deepen our understanding of the ecological functions of GRSP in metal sequestration.
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Simulação de Acoplamento Molecular , Níquel , Níquel/química , Adsorção , Cádmio/química , Sedimentos Geológicos/química , Proteínas Fúngicas/química , Metais Pesados/química , Áreas Alagadas , Poluentes do Solo/química , GlicoproteínasRESUMO
Subcortical ischemic stroke can lead to persistent structural changes in the cerebral cortex. The evolution of cortical structural changes after subcortical stroke is largely unknown, as are their relations with motor recovery, lesion location, and early impairment of specific subsets of fibers in the corticospinal tract (CST). In this observational study, cortical structural changes were compared between 181 chronic patients with subcortical stroke involving the motor pathway and 113 healthy controls. The impacts of acute lesion location and early impairments of specific CSTs on cortical structural changes were investigated in the patients by combining voxel-based correlation analysis with an association study that compared CST damage and cortical structural changes. Longitudinal patterns of cortical structural change were explored in a group of 81 patients with subcortical stroke using a linear mixed-effects model. In the cross-sectional analyses, patients with partial recovery showed more significant reductions in cortical thickness, surface area, or gray matter volume in the sensorimotor cortex, cingulate gyrus, and gyrus rectus than did patients with complete recovery; however, patients with complete recovery demonstrated more significant increases in the cortical structural measures in frontal, temporal, and occipital regions than did patients with partial recovery. Voxel-based correlation analysis in these patients showed that acute stroke lesions involving the CST fibers originating from the primary motor cortex were associated with cortical thickness reductions in the ipsilesional motor cortex in the chronic stage. Acute stroke lesions in the putamen were correlated with increased surface area in the temporal pole in the chronic stage. The early impairment of the CST fibers originating from the primary sensory area was associated with increased cortical thickness in the occipital cortex. In the longitudinal analyses, patients with partial recovery showed gradually reduced cortical thickness, surface area, and gray matter volume in brain regions with significant structural damage in the chronic stage. Patients with complete recovery demonstrated gradually increasing cortical thickness, surface area, and gray-matter volume in the frontal, temporal, and occipital regions. The directions of slow structural changes in the frontal, occipital, and cingulate cortices were completely different between patients with partial and complete recovery. Complex cortical structural changes and their dynamic evolution patterns were different, even contrasting, in patients with partial and complete recovery, and were associated with lesion location and with impairment of specific CST fiber subsets.
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Córtex Motor , Acidente Vascular Cerebral , Humanos , Estudos Transversais , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/complicações , Encéfalo/patologia , Córtex Motor/patologiaRESUMO
BACKGROUND: Chronic inflammation perturbations during pregnancy may impact fetal growth; however, research on the association between dietary inflammation and birth outcomes is limited and inconsistent. OBJECTIVES: This study seeks to assess whether the dietary inflammatory potential is related to birth outcomes among pregnant women in China. METHODS: A total of 7194 mothers aged 17-46 y and their infants in China were included in this cross-sectional study. Dietary intake was assessed by a FFQ, which yielded scores on the energy-adjusted dietary inflammatory index (E-DII). Birth outcomes included birth weight, gestational age, birth weight z score, low birth weight (LBW), macrosomia, preterm birth, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and birth defects. Generalized estimating equation and restricted cubic spline fit each outcome on continuous or quartiles of E-DII after adjusting for covariates. RESULTS: The maternal E-DII ranged from -5.35 to 6.77. Overall, birth weight and gestation age (mean ± SD) were 3267.9 ± 446.7 g and 39.6 ± 1.3 wk, respectively, and the birth weight z score was 0.02 ± 1.14. A total of 3.2% of infants were born with LBW, 6.1% with macrosomia, 3.0% were preterm birth, 10.7% were born SGA, 10.0% were born LGA, and 2.0% were born with birth defects. E-DII was associated with a 9.8 g decrease in birth weight (95% CI: -16.9, -2.6) and a 1.09-fold (95% CI: 1.01, 1.18), 1.11-fold (95% CI: 1.02, 1.21), and 1.12-fold (95% CI: 1.02, 1.24) greater risk of LBW, preterm birth, and birth defects, respectively. The maternal E-DII score was nonlinearly associated with gestational age (P for linearity = 0.009, P for curvature = 0.044). CONCLUSIONS: Among pregnant Chinese women, proinflammatory diets during pregnancy were related to reduced offspring birth weight and an increased risk of LBW, preterm birth, and birth defects. These findings might inform potential prevention strategies for pregnant women in China.
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Dieta , Fenômenos Fisiológicos da Nutrição Materna , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Estudos Transversais , População do Leste Asiático , Retardo do Crescimento Fetal , Macrossomia Fetal/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Inflamação , Nascimento Prematuro/epidemiologia , Aumento de Peso , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
Cisplatin (DDP) resistance limits therapeutic efficacy in patients diagnosed with ovarian cancer. Purvalanol A (Pur) is a novel cyclin-dependent kinase (CDK) inhibitor that has been demonstrated to induce apoptosis in various cancer cells. The present study investigated the effect of the combination treatment of Pur and DDP, and the potential anticancer mechanisms in epithelial ovarian cancer (EOC) cells in vitro and in vivo . We found that Pur enhanced the anti-tumor efficacy of cisplatin in EOC cells. The combination of Pur and DDP had more significant effects on apoptosis induction in EOC cells compared with the individual-treatment groups and the control group. We further demonstrated that the combination of Pur and DDP may trigger apoptosis and autophagy in EOC cells by inducing reactive oxygen species (ROS). And the ROS/Akt/mammalian target of rapamycin signaling pathway as a potential mechanism for the initiation of autophagy induced by combination therapy. Similar results were observed in vivo . These results demonstrated that Pur sensitized the response of EOC cells to cisplatin in vitro and in vivo , reversing the resistance to cisplatin in ovarian cancer.
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Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proliferação de Células , Neoplasias Ovarianas/patologia , Apoptose , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Cognitive dysfunction in patients with infratentorial stroke has been paid little attention. Brainstem stroke may disrupt network connectivity across the whole brain and affect multidomain cognition, but the details of this process remain unclear. The study aimed to investigate the effects of stroke-induced pontine injury on whole-brain network connectivity and cognitive function. We included 47 patients with pontine stroke and 56 healthy comparisons (HC), who underwent cognitive tests and functional magnetic resonance imaging (fMRI). Seven meaningful brain networks were identified using independent component analysis (ICA). Patients with pontine stroke had decreased intra-network functional connectivities (FCs) in the primary perceptual and higher cognitive control networks, including sensorimotor network (SMN), visual network (VIS), default mode network (DMN), and salience network (SAN), as well as decreased inter-network FCs in the primary perceptual (VIS-SMN) and higher cognitive control networks (bilateral frontoparietal networks, rFPN-lFPN). While the FCs between the primary perceptual and higher cognitive control networks (VIS-DMN, VIS-rFPN, VIS-lFPN) were increased. Furthermore, the alterations in these FCs correlated with patients' cognitive measurements. These findings suggested that the infratentorial stroke can induce dysfunctional connectivity in both primary perceptual and higher cognitive control networks at the whole-brain level, which may be attributable to the neural substrates of multidomain cognitive deficits in these patients.
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Disfunção Cognitiva , Acidente Vascular Cerebral , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
Polyclonal anti-D (Rh immune globulin [RhIg]) therapy has mitigated hemolytic disease of the newborn over the past half century, although breakthrough anti-D alloimmunization still occurs in some treated females. We hypothesized that antiviral responses may impact the efficacy of immunoprophylaxis therapy in a type 1 interferon (IFN)-dependent manner and tested this hypothesis in a murine model of KEL alloimmunization. Polyclonal anti-KEL immunoprophylaxis (KELIg) was administered to wild-type or knockout mice in the presence or absence of polyinosinic-polycytidilic acid (poly[I:C]), followed by the transfusion of murine red blood cells (RBCs) expressing the human KEL glycoprotein. Anti-KEL alloimmunization, serum cytokines, and consumption of the transfused RBCs were evaluated longitudinally. In some experiments, recipients were treated with type 1 IFN (IFN-α/ß). Recipient treatment with poly(I:C) led to breakthrough anti-KEL alloimmunization despite KELIg administration. Recipient CD4+ T cells were not required for immunoprophylaxis efficacy at baseline, and modulation of the KEL glycoprotein antigen occurred to the same extent in the presence or absence of recipient inflammation. Under conditions where breakthrough anti-KEL alloimmunization occurred, KEL RBC consumption by inflammatory monocytes and serum monocyte chemoattractant protein-1 and interleukin-6 were significantly increased. Poly(I:C) or type I IFN administration was sufficient to cause breakthrough alloimmunization, with poly(I:C) inducing alloimmunization even in the absence of recipient type I IFN receptors. A better understanding of how recipient antiviral responses lead to breakthrough alloimmunization despite immunoprophylaxis may have translational relevance to instances of RhIg failure that occur in humans.
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Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Metaloendopeptidases/sangue , Metaloendopeptidases/genética , Poli I-C/farmacologia , Animais , Linfócitos T CD4-Positivos/imunologia , Citocinas/sangue , Modelos Animais de Doenças , Eritroblastose Fetal/sangue , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/prevenção & controle , Transfusão de Eritrócitos/efeitos adversos , Feminino , Humanos , Imunização Passiva , Interferon Tipo I/sangue , Isoantígenos/sangue , Isoantígenos/genética , Sistema do Grupo Sanguíneo de Kell/sangue , Sistema do Grupo Sanguíneo de Kell/genética , Glicoproteínas de Membrana/imunologia , Metaloendopeptidases/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Fagocitose/imunologia , GravidezRESUMO
The demand for disposable face masks (DFMs) increased sharply in response to the COVID-19 pandemic. However, information regarding the underlying roles of the largely discarded DFMs in the environment is extremely lacking. This study focused on the pristine and UV-aged DFMs as vectors of metal ions (Pb(â ¡), Cd(â ¡), and Sr(â ¡)). Further, the aging mechanism of DFMs with UV radiation as well as the interaction mechanisms between DFMs and metal ions were investigated. Results revealed that the aging process would help to promote more metal ions adsorbed onto DFMs, which was mainly attributed to the presence of oxygen-containing groups on the aged DFMs. The adsorption affinity of pristine and aged DFMs for the metal ions followed Pb(â ¡) > Cd(â ¡) > Sr(â ¡), which was positively corrected with the electronegativity of the metals. Interestingly, we found that even if DFMs were not disrupted, DFMs had similar or even higher adsorption affinity for metals compared with other existing microplastics. Besides, regarding environmental factors, including salinity and solution pH played a crucial role in the adsorption processes, with greater adsorption capacities for pristine and aged DFMs at higher pH values and low salinity. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and density functional theory further confirmed that the pristine DFMs interacted with the metals mainly through electrostatic interaction, while electrostatic interaction and surface complexation jointly regulated the adsorption of the metals onto aged DFMs. Overall, these findings would help to evaluate environmental behaviors and risks of DFMs associated with metals.
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Glomalin-related soil protein (GRSP), a microbial product that can be used as a bioflocculant, is critical to metal sequestration in the ecosystem. However, the relationship between GRSP and heavy metal has not been well explored. In this study, the adsorption behaviors and mechanisms of Pb(II) and Zn(II) ions on GRSP were investigated. Results reveal that the Pb(II) and Zn(II) adsorption closely conform to the pseudo second-order model, which indicates that the chemisorption of GRSP occurred after intra-particle diffusion. The adsorption process is influenced by the degree of pollution, pH value, GRSP content in the environment. In addition, scanning electron microscopy coupled with microanalysis (SEM-EDX) reveals that the surface structure of GRSP is irregularly blocky or flaky and metal ions are uniformly distributed on the surface of GRSP. Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) analysis show that the carboxyl and nitro groups on GRSP act as ligands to form complexes with two divalent metal ions. The interaction between GRSP and the metals is mainly surface complexation. This research further reveals the dynamic response of its structural components when GRSP sequestrates heavy metals in mangrove sediment and aqueous ecosystems, demonstrating a new perspective for the transport and transformation of heavy metals onto GRSP.
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Metais Pesados , Solo , Adsorção , Ecossistema , Cinética , Chumbo , Metais Pesados/análise , Solo/química , Espectroscopia de Infravermelho com Transformada de Fourier , ZincoRESUMO
BACKGROUND AND PURPOSE: Cortical beta oscillations are reported to serve as robust measures of the integrity of the human motor system. Their alterations after stroke, such as reduced movement-related beta desynchronization in the primary motor cortex, have been repeatedly related to the level of impairment. However, there is only little data whether such measures of brain function might directly relate to structural brain changes after stroke. METHODS: This multimodal study investigated 18 well-recovered patients with stroke (mean age 65 years, 12 males) by means of task-related EEG and diffusion-weighted structural MRI 3 months after stroke. Beta power at rest and movement-related beta desynchronization was assessed in 3 key motor areas of the ipsilesional hemisphere that are the primary motor cortex (M1), the ventral premotor area and the supplementary motor area. Template trajectories of corticospinal tracts (CST) originating from M1, premotor cortex, and supplementary motor area were used to quantify the microstructural state of CST subcomponents. Linear mixed-effects analyses were used to relate tract-related mean fractional anisotropy to EEG measures. RESULTS: In the present cohort, we detected statistically significant reductions in ipsilesional CST fractional anisotropy but no alterations in EEG measures when compared with healthy controls. However, in patients with stroke, there was a significant association between both beta power at rest (P=0.002) and movement-related beta desynchronization (P=0.003) in M1 and fractional anisotropy of the CST specifically originating from M1. Similar structure-function relationships were neither evident for ventral premotor area and supplementary motor area, particularly with respect to their CST subcomponents originating from premotor cortex and supplementary motor area, in patients with stroke nor in controls. CONCLUSIONS: These data suggest there might be a link connecting microstructure of the CST originating from M1 pyramidal neurons and beta oscillatory activity, measures which have already been related to motor impairment in patients with stroke by previous reports.
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Ritmo beta/fisiologia , Córtex Motor/fisiopatologia , Tratos Piramidais/patologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodosRESUMO
Stroke is a major cause of vascular cognitive dysfunction, such as memory impairment. We aimed to explore the neural substrates underlying verbal memory impairment in subcortical stroke patients by the methods of voxel-wise cerebral blood flow (CBF) and the functional covariance network (FCN). Sixty patients with chronic subcortical stroke and 60 normal controls (NCs) were recruited into this study. We used a three-dimensional pseudo-continuous arterial spin-labeling imaging to measure alterations in CBF and FCNs. We mapped the overall CBF alterations in a voxel-wise manner and compared CBF measurements using a two-sample t test. Correlations between CBF and verbal memory were also investigated. Subsequently, we constructed FCNs by calculating the correlation between specific regions and all other voxels of a whole brain, separately within the two groups. Thereafter, by comparing differences of the FCN patterns between the patient and NC groups, we investigated the connection alterations within the FCN maps. The stroke patients showed verbal short-term memory (VSTM) deficits compared to NCs. The patients exhibited decreased CBF in the ipsilesional insula and ventral sensorimotor network, and increased CBF in contralesional frontal cortical and subcortical regions (putamen and thalamus). Meanwhile, the CBF in the ipsilesional insula was positively correlated, and the contralesional frontal cortical was negativity correlated, with VSTM scores. Moreover we found that stroke patients exhibited disordered connection within FCNs compared to NCs. The study suggests that the underlying imaging biomarker of VSTM impairment in patients with subcortical stroke was associated with disconnection of the frontal lobe network.
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Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/normas , Rede Nervosa/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/irrigação sanguínea , Rede Nervosa/fisiopatologia , Prognóstico , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Glomalin-related soil protein (GRSP), a ubiquitous microbial product, plays a crucial role in particle aggregation and metal adsorption, but the underlying mechanisms remain unknown. Here, GRSP fraction was extracted from estuarine ecosystems and systematically characterized to elucidate the aggregation mechanisms and its impact on coastal environment improvement. We found that GRSP fraction (gravimetric mass of extracted GRSP, 5.1-24.3 mg g-1) was a globally relevant novel bioflocculant and that protein (linked to Bradford protein assay, 1.64-4.37 mg g-1) was the active flocculant constituent. The zeta potential, FTIR, XPS, and 13C NMR analyses identified its key constituents and structure, and revealed that the charge neutralization and bridging were GRSP fraction aggregation mechanisms. Thermogravimetric-infrared spectrometry analysis showed that GRSP fraction was highly thermostable, and the main volatile pyrolysis products included H2O, CO2, CO, and CH4. The SEM-EDX and XPS Fe valence spectroscopy suggested that GRSP fraction contained rich Fe (11.91 ± 0.48%) and could form Fe-rich flocs with particles. We also found that GRSP fraction has a high adsorption capacity (76-95%) for Cu, Zn, Pb and Cd, and its flocculation properties provide new insights into metal adsorption. The analysis of particle aggregation mechanism and its metal adsorption capacity is of great significance to elucidate the role of GRSP fraction in coastal environment improvement.
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Ecossistema , Solo , Proteínas Fúngicas , Microbiologia do SoloRESUMO
BACKGROUND AND PURPOSE: Motor deficit is the most common disability after stroke, and early prediction of motor outcome is critical for early interventions. Here, we constructed a fine map of the corticospinal tract (CST) for early prediction of motor outcome and for understanding the secondary brain changes after subcortical stroke. METHODS: Diffusion spectrum imaging data from 50 healthy adults were used to reconstruct fine maps of CST with different origins, including primary motor area (M1), primary sensory area (S1), premotor cortex, and supplementary motor area (SMA). Their diffusion properties correlated with motor functions in healthy adults. The impacts of the impairments of different CST on motor outcomes and on structural and functional changes of brain were investigated in 136 patients with subcortical stroke by combining CST damage-symptom association study and voxel-based lesion-symptom mapping. RESULTS: In healthy adults, the isotropy of M1 fiber correlated with walking endurance and that of SMA fiber with motor dexterity. In chronic stroke patients, the integrity of M1 and SMA fibers showed the most significant correlation with motor deficits. The percentage of early damage of M1 and SMA fibers correlated with that of chronic motor deficits. Voxel-based lesion-symptom mapping revealed that acute stroke lesions in the bilateral M1 and right SMA fibers were associated with chronic motor deficits. The early damage of M1 fiber negatively correlated with the integrity of M1-M1 fiber, and the early damage of SMA fiber negatively correlated with gray matter volume of the contralateral cerebellum in the chronic stage. CONCLUSIONS: The CST that originated from the M1 and SMA are closely associated with motor outcomes and brain structural changes, and the fine maps of CST from these 2 cortical areas are useful in assessing and predicting long-term motor outcome in patients with subcortical stroke.
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Mapeamento Encefálico/métodos , Atividade Motora/fisiologia , Córtex Motor/fisiopatologia , Tratos Piramidais/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Neuroimagem/métodos , Tratos Piramidais/diagnóstico por imagem , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Only a fraction of red blood cell (RBC) transfusion recipients form alloantibodies, and variables determining responsiveness or nonresponsiveness are poorly understood. We and others have previously shown in animal models that pretreatment with toll-like receptor agonists that mimic different types of infections impacts the magnitude or frequency of RBC alloantibody responses. We hypothesized that influenza infection, coexistent with transfusion, would impact responses to transfused RBCs in a manner dependent on Type 1(α/ß) interferon (IFN) signaling and tested this in a murine model. STUDY DESIGN AND METHODS: Wild-type mice or mice lacking the ability to respond to Type 1 IFN were infected with influenza prior to the transfusion of transgenic murine RBCs (K1) expressing the human KEL glycoprotein or the triple fusion HOD protein. Alloantibody responses were measured longitudinally after transfusion by flow cytometric crossmatch, and posttransfusion RBC recovery and survival was evaluated. RESULTS: Influenza-infected mice transfused with K1 RBCs developed robust anti-KEL alloantibodies, whereas animals transfused in the absence of infection remained nonresponders; influenza-associated RBC alloimmunization was also observed after transfusion of HOD RBCs. Recipient Type 1 IFN production was critical to the mechanism of action of influenza-induced RBC alloimmunization, with alloimmunization being significantly decreased in mice unable to sense Type 1 IFN (through antibody blockade or genetic approaches). CONCLUSION: These and other data suggest that Type 1 IFN responses to toll-like receptor agonists or infections regulate RBC alloantibody responses. Studies investigating whether such a correlation exists in humans may be informative.
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Transfusão de Eritrócitos , Eritrócitos/imunologia , Vírus da Influenza A/imunologia , Interferon Tipo I/imunologia , Sistema do Grupo Sanguíneo de Kell/imunologia , Infecções por Orthomyxoviridae/imunologia , Transdução de Sinais/imunologia , Reação Transfusional/imunologia , Animais , Interferon Tipo I/genética , Sistema do Grupo Sanguíneo de Kell/genética , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/transmissão , Transdução de Sinais/genética , Reação Transfusional/genética , Reação Transfusional/virologiaRESUMO
During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/ß) are induced in inflammatory conditions associated with increased alloimmunization. By developing a new transgenic murine model, we demonstrate that signaling through the IFN-α/ß receptor is required for inflammation-induced alloimmunization. Additionally, mitochondrial antiviral signaling protein-mediated signaling through cytosolic pattern recognition receptors was required for polyinosinic-polycytidylic acid-induced IFN-α/ß production and alloimmunization. We further report that IFN-α, in the absence of an adjuvant, is sufficient to induce RBC alloimmunization. These findings raise the possibility that patients with IFN-α/ß-mediated conditions, including autoimmunity and viral infections, may have an increased risk of RBC alloimmunization and may benefit from personalized transfusion protocols and/or targeted therapies.
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Eritrócitos/imunologia , Inflamação/imunologia , Interferon Tipo I/imunologia , Isoanticorpos/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antígenos/imunologia , Autoimunidade , Transfusão de Eritrócitos/efeitos adversos , Humanos , Interferon Tipo I/metabolismo , Camundongos , Camundongos Transgênicos , Poli I-C/administração & dosagem , Poli I-C/imunologia , Receptor de Interferon alfa e beta/metabolismo , Transdução de SinaisRESUMO
In the present study, a set of pot culture experiments was conducted to reveal how the metabolism process of phenolic compounds was affected by cadmium (Cd) and zinc (Zn) and to further uncover heavy metal tolerance mechanisms in Kandelia obovata. After 60d of treatment, the biomass and chlorophyll a content in the leaves were suppressed, but total phenolic compounds in roots and leaves were improved by the increasing gradient of Cd or Zn concentrations; Total phenolic compounds significantly increased by 3.6-44.6% in the roots, and by 0.4-126.6% in the leaves. At the meantime, the activity of Shikimate dehydrogenase (SKDH), cinnamyl alcohol dehydrogenase (CAD), and polyphenol oxidase (PPO) in the roots increased by 11.2-307.6%, 12.4-175.4% and -â¯2.7-392.8%, and the results were 3.4-69.5%, 1.7-40.0%, 16.0-99.7% in the leaves. Higher toxicity of Cd than Zn, as well as slight alleviating effect of 100â¯mgâ¯kg-1 Zn on 2.5â¯mgâ¯kg-1 Cd were found. Additionally, a significantly positive correlation coefficients for relationship between phenolic metabolism related enzyme activity and Cd/Zn contamination levels was found, and leaf SKDH, leaf CAD, and leaf PPO activities were moderately correlated with leaf Cd (râ¯=â¯0.39, râ¯=â¯0.43, and râ¯=â¯0.57, respectively) and leaf Zn (râ¯=â¯0.44, râ¯=â¯0.41, râ¯=â¯0.19, respectively) content, which indicate that Cd and Zn play a previously unrecognized but major role in phenolic compounds synthesis, transport, and metabolism in K. obovata. The results also provided evidence that the application of high levels of Cd and Zn was accompanied by three phenolic metabolism pathways participating in heavy metal tolerance process.
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Cádmio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/metabolismo , Rhizophoraceae/efeitos dos fármacos , Zinco/toxicidade , Biodegradação Ambiental , Cádmio/metabolismo , Clorofila A/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Rhizophoraceae/crescimento & desenvolvimento , Rhizophoraceae/metabolismo , Zinco/metabolismoRESUMO
Purpose To investigate neural substrates underlying attention deficit in patients with chronic subcortical stroke by combining voxel-based lesion-symptom mapping (VLSM) and diffusion-tensor (DT) tractography. Materials and Methods Institutional review board approval and written informed consent were obtained. Diffusion magnetic resonance imaging data were prospectively acquired from August 1, 2014, to March 30, 2015, in 49 patients (32 men, 17 women; mean age, 55.7 years ± 8.0; age range, 40-71 years) with subcortical infarctions in the basal ganglia and neighboring regions and 52 control subjects (30 men, 22 women; mean age, 54.4 years ± 7.5; age range, 40-68 years). A modified version of the attention network test was used to assess visual attention function. On the basis of the lesion map at the acute stage, VLSM was used to identify lesion locations related to attention deficit in patients with stroke. DT tractography then was used to determine the responsible impaired connections by using diffusion data at the chronic stage (>6 months after stroke). Results When compared with control subjects, patients with chronic stroke exhibited prolonged reaction time (RT) of correct responses (P = .009). VLSM revealed that acute stroke lesion in the right caudate nucleus and nearby white matter (found in seven patients) was correlated with the prolonged RT (P < .05). DTT showed that the responsible lesion was located in the right thalamic- and caudate-prefrontal pathways in control subjects. The subgroup with right-sided brain damage had significantly decreased fractional anisotropy in these pathways (P < .001), which were correlated with the prolonged RT (P = .009 for the thalamic-prefrontal pathway, P < .001 for the caudate-prefrontal pathway). Conclusion Thalamic-prefrontal and caudate-prefrontal pathways impaired by stroke lesions appear to underlie attention deficit in patients with subcortical stroke in the right hemisphere.
Assuntos
Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Red blood cell (RBC) alloimmunization is a serious complication of transfusion or pregnancy. Despite the widespread use of Rh immune globulin to prevent pregnancy associated anti-D alloimmunization, its mechanism of action remains elusive. We have previously described a murine model in which immunoprophylaxis with polyclonal anti-KEL sera prevents alloimmunization in wild-type recipients transfused with transgenic murine RBCs expressing the human KEL glycoprotein. To investigate the mechanism of action, we have now evaluated the outcome of immunoprophylaxis treatment in mice lacking Fcγ receptors (FcγRs), complement (C3), both, or none. Whereas polyclonal anti-KEL sera completely prevented alloimmunization in wild-type and single-knockout (KO) mice lacking FcγRs or C3, double-KO mice lacking both FcγRs and C3 became alloimmunized despite immunoprophylaxis. Rapid clearance of essentially all transfused RBCs with detectable KEL glycoprotein antigen occurred within 24 hours in wild-type and single-KO recipients treated with immunoprophylaxis, with the transfused RBCs remaining in circulation having minimal KEL glycoprotein antigen detectable by flow cytometry or western blot. In contrast, transfused RBCs with the KEL glycoprotein antigen fully intact continued to circulate for days in double-KO mice despite treatment with immunoprophylaxis. Further, in vitro phagocytosis assays showed no consumption of opsonized murine RBCs by double-KO splenocytes. Taken in combination, our data suggest that modulation of the KEL antigen (and potentially RBC clearance) by redundant recipient pathways involving both FcγRs and C3 may be critical to the mechanism of action of polyclonal anti-KEL immunoprophylaxis. These findings could have implications for the development of immunoprophylaxis programs in humans.
Assuntos
Antígenos/metabolismo , Imunização , Glicoproteínas de Membrana/imunologia , Metaloendopeptidases/imunologia , Animais , Anticorpos Anti-Idiotípicos/metabolismo , Transfusão de Sangue , Western Blotting , Complemento C3/metabolismo , Cruzamentos Genéticos , Eritrócitos/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Opsonizantes/metabolismo , Fagocitose , Receptores Imunológicos/metabolismo , Baço/citologiaRESUMO
OBJECTIVES: Olfactory dysfunction (ODF) has been reported in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the comparison of olfactory function and olfactory-related gray matter (GM) between patients with NMO and MS needed to be further elucidated. MATERIALS AND METHODS: Thirty-seven patients with NMO and 37 with MS were enrolled. Olfactory function was evaluated with a Japanese T&T olfactometer test kit, and the neuroanatomical features of olfactory-related GM were assessed using voxel-based morphometry. RESULTS: Olfactory deficits were found in 51.4% of patients with NMO and 40.5% of patients with MS. Patients with NMO with ODF had significantly smaller olfactory bulbs than patients with MS with ODF (p = 0.031). Olfactory-related GM atrophy was found in patients with NMO in several regions of the right orbitofrontal cortex and right superior frontal gyrus; in patients with MS, reduced GM volume was found in the right parahippocampal gyrus and piriform cortex (p < 0.05, cluster size > 200 voxels). CONCLUSIONS: Olfactory deficits are common in both NMO and MS. However, the neuroanatomical features related to olfactory deficits differ greatly between the two diseases.