To investigate age-related brain morphological changes of boys with high functioning autism (HFA).
Forty-six medication-naive boys with HFA and 48 age-matched typically developing boys (4-12 years ...old) were included in this study. Structural brain images were processed with FreeSurfer to calculate the brain morphometric features including regional volume, surface area, average cortical thickness, and Gaussian curvature. General linear model was used to identify significant effects of diagnosis and age-by-diagnosis interaction. Correlations between age and the brain morphometric variables of significant clusters were explored.
Primarily, most of the regions with statistically significant intergroup differences were located in the temporal lobe gyri. Importantly, the volume of bilateral superior temporal gyrus (STG) and the average cortical thickness of the right STG demonstrated significantly age-related intergroup differences. Further age-stratified analysis also revealed morphological alterations of STG among subgroups of preschool and school-aged children with or without HFA.
The findings demonstrated abnormal age-related volume and cortical thickness atrophy of the STG in HFA children, which reflect brain development trajectories of ASD may initiate to diverge from early overgrowth in childhood period. The anatomical localization of specific brain regions would help us better understand the neurobiology alterations of HFA patients and indicate the effect of age should be carefully delineated and examined in future studies about HFA.
Medulloblastoma (MB) is the most common pediatric embryonal tumor. Accurate identification of cerebral spinal fluid (CSF) dissemination is important in prognosis prediction. Both MRI of the central ...nervous system (CNS) and CSF cytology will appear false positive and negative. Our objective was to investigate the added value of preoperative-enhanced T1-weighted image-based radiomic features to clinical characteristics in predicting preoperative CSF dissemination for children with MB.
This retrospective study included 84 children with histopathologically confirmed MB between November 2006 and November 2018 (training cohort, n=60; internal validation cohort, n=24). A set of cases between December 2018 and February 2020 were used for external validation (n=40). The children with normal head and spine magnetic resonance images (MRI) and no subsequent dissemination in 1 year were diagnosed as non-CSF dissemination. The CSF dissemination was manifested as intracranial or intraspinal nodular-enhanced lesions. Clinical features were collected, and conventional MRI features of preoperative head MRI examinations were evaluated. A total of 385 radiomic features were extracted from preoperative-enhanced T1-weighted images. Minimum redundancy, maximum correlation, and least absolute shrinkage and selection operator were performed to select the features with the best performance in predicting preoperative CSF dissemination. A combined clinical-MRI radiomic prediction model was developed using multivariable logistic regression. Receiver operating curve analysis (ROC) was used to validate the predictive performance. Nomogram and decision curve analysis (DCA) were developed to evaluate the clinical utility of the combined model.
One clinical and nine radiomic features were selected for predicting preoperative CSF dissemination. The combined model incorporating clinical and radiomic features had the best predictive performance in the training cohort with an AUC of 0.89. This was validated in the internal and external cohorts with AUCs of 0.87 and 0.73. The clinical utility of the model was confirmed by a clinical-MRI radiomic nomogram and DCA.
The combined model incorporating clinical, conventional MRI, and radiomic features could be applied to predict preoperative CSF dissemination for children with MB as a noninvasive biomarker, which could aid in risk evaluation.
Abstract
The extensive growth of large-scale flexible high voltage direct current (HVDC) transmission systems compromises the strength of the alternating current (AC) power grid. Sub-synchronous ...oscillations will likely arise within such flexible HVDC systems, which would significantly threaten the grand electric power system’s stable operation. A current-type enhanced virtual inertia control is proposed to suppress the sub-synchronous oscillations induced by a weak AC power grid in the modular multilevel converter (MMC)-based HVDC systems. Firstly, a small signal model of MMC is established to study the stability of the system under a weak power grid. Focally, a current-mode virtual inertial control is proposed to suppress the AC power grid’s sub-synchronous oscillation by directly taking the grid current as the virtual inertia control variable. Finally, the proposed virtual inertia control approach is verified using both offline and real-time simulation based on the Chongqing-Hubei flexible MMC-HVDC transmission system. The simulation results demonstrate that the proposed current-mode virtual inertia control strategy can efficiently suppress sub-synchronous oscillations in the MMC-HVDC system interacting with a weak AC grid, which enhances the stability and reliability of the power system.
Tree-type hydraulic fracturing (TTHF) is a new technology that can enhance the permeability of coal seams in a balanced manner and increase the coalbed methane production rate. However, the ...heterogeneity of coal seams is a major challenge in achieving balanced permeability enhancement by TTHF. Traditional methods based on digital image processing are difficult to apply in practice. To address these challenges, we proposed a 2D numerical model of coal seams based on the combined finite-discrete element method (FDEM). The elastic modulus of the coal seams obeys a Weibull distribution, and the coal heterogeneity was quantified by an index m. The effects on the fracture initiation pressure, the fracturing influence range, and displacements of TTHF were analyzed from four aspects, including the homogeneity index of coal, the arrangement angle of branch boreholes, the horizontal stress difference, and the injection rate of the fracturing fluid. The results show that TTHF has a significant effect on the balanced permeability enhancement in coal reservoirs, particularly with strong heterogeneity, and the best permeability enhancement for TTHF is achieved when the branch boreholes are arranged at 45°. The branch boreholes are prefabricated in advance to create a pressure relief area around the injection point, and the hydraulic fracture propagation is affected by the horizontal stress difference only when the fracturing influence range exceeds this area. When the horizontal stress difference increases from 0 to 4 MPa, its fracture initiation pressure increases from 8.93 to 10.86 MPa, with an increase of 21.61%. In addition, the initial stage of fluid injection was found to be crucial for achieving balanced permeability enhancement in TTHF, and a higher injection rate can expand the fracturing influence range. The numerical model has profound implications for the field application of TTHF technology.
Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism ...and how levodopa, the standard treatment in PD, regulates NVC is largely unknown.
A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed.
Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications.
Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.
•PD patients exhibited neurovascular coupling (NVC) alteration in the striato-thalamo-cortical motor circuit and motor control regions.•The NVC dysfunction could be driven by dopaminergic and nondopaminergic systems (serotoninergic, opioid, and cholinergic).•Levodopa ameliorated abnormal NVC in most of these regions, where there were primarily neuronal activity changes with limited blood perfusion modifications.
Background and purpose
The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both ...postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system.
Methods
A total of 84 PD patients and 82 normal controls were enrolled. Each participant underwent motor and cognitive assessments. Diffusion tensor imaging was used to detect structural abnormalities in the cBF system. The cBF was segmented using FreeSurfer, and its fiber tract was traced using probabilistic tractography. To provide information on extracellular water accumulation, free‐water fraction (FWf) was quantified. FWf in the cBF and its fiber tract, as well as cortical projection density, were extracted for statistical analyses.
Results
Patients had significantly higher FWf in the cBF (p < 0.001) and fiber tract (p = 0.021) than normal controls, as well as significantly lower cBF projection in the occipital (p < 0.001), parietal (p < 0.001) and prefrontal cortex (p = 0.005). In patients, a higher FWf in the cBF correlated with worse PIGD score (r = 0.306, p = 0.006) and longer Trail Making Test A time (r = 0.303, p = 0.007). Attentional function (Trail Making Test A) partially mediated the association between FWf in the cBF and PIGD score (indirect effect, a*b = 0.071; total effect, c = 0.256; p = 0.006).
Conclusions
Our findings suggest that degeneration of the cBF system in PD, from the cBF to its fiber tract and cortical projection, plays an important role in cognitive−motor interaction.
•The mixtures of mycotoxins significantly increased epithelial permeability, altered TJ proteins morphology and structures.•Mixtures of mycotoxins significantly modulated MUC5AC and MUC5B mRNA levels ...and protein secretion.•The damage of intestinal integrity caused by mycotoxins was correlated to the change of the TJ proteins location.•The damage of intestinal integrity caused by mycotoxins was correlated to the decrease of mucin secretion.
Aflatoxin M1 (AFM1), ochratoxin A (OTA), and zearalenone (ZEA) are mycotoxins commonly found in milk. Mycotoxin contamination has caused food safety concerns worldwide since most of the toxic effects in humans are serious. The combined toxic effects of these mycotoxins on intestinal epithelial cells have not been reported. Herein, we investigated the combined effects of AFM1, OTA, and ZEA on intestinal integrity and define the underlying mechanisms(s) of their effects in Caco-2/HT29-MTX co-cultures. Our results showed that the mixtures of AFM1 + OTA, AFM1 + ZEA, and AFM1 + ZEA + OTA significantly increased epithelial permeability. Immunofluorescence analysis and transmission electron microscopy revealed that mycotoxins altered TJ proteins morphology and disrupted their structures. Also, the present study showed that mixtures of mycotoxins significantly modulated MUC5AC and MUC5B mRNA levels and protein secretion. This study demonstrated that the effects of mixtures of mycotoxins on intestinal barrier function were more significant than AFM1 alone. More importantly, the damage of intestinal integrity caused by mycotoxins was correlated to the change of the TJ proteins location and the decrease of mucin secretion. Mixtures of AFM1, OTA, and ZEA in food might pose a health risk to consumers, particularly in children, and toxin risks should be considered.
Although fuel cell (FC) has been regarded as promising “green” power generator, the Pt-based catalysts in the FC hampered their further development for its high cost and scarcity. Direct methanol ...fuel cell (DMFC) as another kind of proton exchange membrane fuel cell (PEMFC) has been manifested that Pd also performs a certain activity for methanol oxidation reaction (MOR). To better know the mechanism of MOR, we present a DFT study on the first step reaction of MOR on the Pd(111). The results show that methanol prefers to physically adsorb on the Pd(111) through oxygen atom, while the dehydrogenated hydrogen atoms can adsorb either on face-cantered cubic (FCC) or hexagonal close packed (HCP) sites. The intermediate products will form a much stronger interaction with the Pd(111) since they contain more unsaturated bonds. The energy barrier of O-H bond scission is most favourable, while the C-O bond is unfavourable in the first step of MOR.
Rest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe ...progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear.
This study included 57 ET patients (40 without rest tremor (ETWR), 17 with rest tremor (ETRT)), 68 PD patients (34 without rest tremor (PDWR), 34 with rest tremor (PDRT)), and 62 normal controls (NC). Fixel-based analysis was used to evaluate the structural changes of white matter in rest tremor in these different diseases.
The fiber-bundle cross-section (FC) of the right non-decussating dentato-rubro-thalamic tract and several fibers outside the dentato-rubro-thalamic pathway in ETWR were significantly higher than that in NC. The fiber density and cross-section of the left nigro-pallidal in PDWR is significantly lower than that in NC, while the FC of bilateral nigro-pallidal in PDRT is significantly lower than that in NC.
ET patients with pure action tremor showed over-activation of fiber tracts. However, when superimposed with rest tremor, ET patients no longer exhibited over-activation of fiber tracts, but rather showed a trend of fiber tract damage. Except for the nigro-pallidal degeneration in all PD, PDRT will not experience further deterioration in fiber organization. These results provide important insights into the unique effects of rest tremor on brain fiber architecture in ET and PD.
•Different effects of rest tremor on brain fiber structure in ET and PD patients.•When superimposed with rest tremor, ET patients exhibited a potential for fiber tract damage.•Except for the SN-GP degeneration in all PD, PDRT may not have worse fiber organization.
Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors ...and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients. Furthermore, we observed that Cyr61 could effectively stimulate Jurkat (T ALL cell lines), Nalm-6 (B ALL cell lines), and primary ALL cell survival. Mechanistically, we showed that Cyr61 stimulated ALL cell survival via the AKT/NF-κB signaling pathways and the consequent up-regulation of Bcl-2. Taken together, our study is the first to reveal that Cyr61 is elevated in ALL and promotes cell survival through the AKT/NF-κB pathway by up-regulating Bcl-2. Our findings suggest that Cyr61 plays an important role in the pathogenesis of ALL.
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