Search

Mixed findings exist in studies comparing brain responses to reward in adolescents and adults. Here we examined the trajectories of brain response, functional connectivity and task-modulated network properties during reward processing with a large-sample longitudinal design. Participants from the IMAGEN study performed a Monetary Incentive Delay task during fMRI at timepoint 1 (T1; n = 1304, mean age=14.44 years old) and timepoint 2 (T2; n = 1241, mean age=19.09 years). The Alcohol Use Disorders Identification Test (AUDIT) was administrated at both T1 and T2 to assess a participant's alcohol use during the past year. Voxel-wise linear mixed effect models were used to compare whole brain response as well as functional connectivity of the ventral striatum (VS) during reward anticipation (large reward vs no-reward cue) between T1 and T2. In addition, task-modulated networks were constructed using generalized psychophysiological interaction analysis and summarized with graph theory metrics. To explore alcohol use in relation to development, participants with no/low alcohol use at T1 but increased alcohol use to hazardous use level at T2 (i.e., participants with AUDIT≤2 at T1 and ≥8 at T2) were compared against those with consistently low scores (i.e., participants with AUDIT≤2 at T1 and ≤7 at T2). Across the whole sample, lower brain response during reward anticipation was observed at T2 compared with T1 in bilateral caudate nucleus, VS, thalamus, midbrain, dorsal anterior cingulate as well as left precentral and postcentral gyrus. Conversely, greater response was observed bilaterally in the inferior and middle frontal gyrus and right precentral and postcentral gyrus at T2 (vs. T1). Increased functional connectivity with VS was found in frontal, temporal, parietal and occipital regions at T2. Graph theory metrics of the task-modulated network showed higher inter-regional connectivity and topological efficiency at T2. Interactive effects between time (T1 vs. T2) and alcohol use group (low vs. high) on the functional connectivity were observed between left middle temporal gyrus and right VS and the characteristic shortest path length of the task-modulated networks. Collectively, these results demonstrate the utility of the MID task as a probe of typical brain response and network properties during development and of differences in these features related to adolescent drinking, a reward-related behaviour associated with heightened risk for future negative health outcomes. • Imaging data during reward anticipation at T1 (age 14) and T2 (age 19) was compared. • Brain response decreased in subcortical areas and increased in cortical areas at T2. • Functional connectivity (FC) with the ventral striatum increased at T2. • Topological efficiency of task-modulated network increased at T2. • The developmental pattern was altered in those who increased drinking most at T2. [ABSTRACT FROM AUTHOR]

Ischemic stroke in rodents is usually induced by intraluminal occlusion of the middle cerebral artery (MCA) via the external carotid artery (ECA) or the common carotid artery (CCA). The latter route requires permanent CCA occlusion after ischemia, and here, we assess its effects on long-term outcomes. Transient occlusion of MCA and CCA was performed at normal body temperature. After 90 min of ischemia, mice were randomized to permanent CCA occlusion or no occlusion (control group). Body weight, and motor and sensory functions, ie, pole test, adhesive tape removal, and elevated plus maze, were evaluated at 24 h, and at 7 and 28 days after stroke. Infarct volume, apoptosis, and activation of astrocytes and microglia were assessed at 4 weeks by an investigator blinded to groups. The Morris water maze test was performed at 3 weeks in the second experiment. One mouse died at 4 days, and the other mice survived with persistent neurologic deficits. CCA-occluded mice exhibited delayed turn on the pole at 24 h and decreased responses to the von Frey filament, and spent more time on the pole at 7 and 28 days than the control group. Infarction, hemispheric atrophy, glial activation, and apoptotic neuronal death were present in all mice, and no intra-group difference was found. However, CCA-occluded mice had a significantly poorer performance in the Morris water maze compared to the control group, which showed an adverse effect of post-ischemia CCA occlusion on cognition. Thus, the model selection should be well considered in preclinical efficacy studies on stroke-induced vascular dementia and stroke with Alzheimer's disease. • CCA occlusion worsens stroke-induced long-term cognitive deficits. • CCA occlusion does not worsen long-term sensorimotor deficits and infarct size. • CCA occlusion does not worsen post-stroke inflammation and apoptosis at 4 weeks. • Transcranial MCA occlusion was used to avoid destroying the carotid artery branches. • MCAO model with CCA filament insertion is not feasible in cognitive function study. [ABSTRACT FROM AUTHOR]

• Nutmeg exposure may cause dose- and duration-dependent liver damage. • Inflammatory cell infiltration and hepatocyte necrosis were dose- and duration-related. • Elevated serum AST and ALT levels were related to nutmeg dose and exposure duration. • Nutmeg exposure caused differential levels of metabolites related to liver function. Incidences of abuse and poisoning have been reported for nutmeg, a household spice made from grinding the seed of Myristica fragrans , owing to its hallucinogenic properties. However, there have been no reports on nutmeg hepatotoxicity in relation to dose and duration of exposure. To investigate the hepatotoxicity of different nutmeg exposure durations and doses, male mice were administered daily with normal saline, 1.0 g/kg nutmeg, or 4.0 g/kg nutmeg by intragastrical gavage for either 7 or 14 days (for a total of six treatment groups, n = 6). Body weight of each mouse was monitored daily. Histological analysis of liver tissues was performed using hematoxylin and eosin (H&E) staining to investigate the morphological changes in hepatocytes. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined using enzyme-linked immunosorbent assay (ELISA) to investigate liver function. Metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed between treatment groups for identifying differential metabolites. Mice in the nutmeg exposure groups exhibited slow growth trends, hepatocyte damage, and significantly elevated serum AST and ALT levels associated with nutmeg dose and exposure duration. Metabolomics and KEGG enrichment pathway analyses also revealed differential levels of some metabolites related to liver function upon nutmeg exposure. Therefore, the present study reasonably speculates that nutmeg exposure may cause liver damage and affect liver function depending on the dose and duration. [ABSTRACT FROM AUTHOR]

Based on the shape descriptors of image contour, this paper proposes an automatic fault recognition method for Brake-Shoe-Key (BSK) losing of freight train. The method contained two phase, one is the positioning of the feature region, the other is recognition of the feature for the BSK losing. In the position phase, a direction-adaptive grey projection method followed by an enhancing process was put forwarded for the initial positioning of image feature region of the Brake Shoe. And then based on edge information, a threshold-relaxation method was adopted to precisely extract the contour of the Braked Shoe. In the recognition phase, besides some ordinary shape descriptors such as rectangular degree, solidity, compactness, circularity, etc., two new shape descriptors, respectively named as contour smoothness and contour concave–convex were proposed to establish the recognition characters vector. At last, the Support Vector Machine (SVM) was used in the classifier for BSK losing fault recognition. Experiments demonstrated that the proposed algorithm is not sensitive to image noise and performed well on images with complex background and disturbance such as blur, poor illumination, excess exposure, etc. [ABSTRACT FROM AUTHOR]

A new type of linear copolymers, poly(ortho ester amino alcohols) (POEAAs), has been synthesized by ring-opening polymerization between diglycidyl ethers and amine monomer with ortho ether bonds. POEAAs have uniform distribution of tertiary amine main-chains along with abundant hydroxyl groups and acid-cleavable tertiary amine side-chains. POEAA1 and 2 containing different diglycidyl ether moieties were prepared to regulate their hydrophilicity and DNA condensation ability. POEAAs could efficiently condense plasmid DNA into nanoparticles, which have much lower cytotoxicity than branched PEI (25 KDa). The breakage of tertiary amines in side chains of POEAAs caused by hydrolysis of ortho ester bonds at mildly acid-pHs could obviously facilitate the release of DNA from the polyplexes. More significantly, the effective transfection on 293T cells mediated by POEAAs was not negatively affected by 10% serum concentration because of their improved serum tolerance. [ABSTRACT FROM AUTHOR]