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Salient stimuli can capture attention in a bottom-up manner; however, this attentional capture can be suppressed in a top-down manner. It has been shown that individuals with high working memory capacity (WMC) can suppress salient‑but-irrelevant distractors better than those with low WMC; however, neural substrates underlying this difference remain unclear. To examine this, participants with high or low WMC (high-/low-WMC, n = 44/44) performed a visual search task wherein a color singleton item served as a salient distractor, and underwent structural and resting-state functional magnetic resonance imaging scans. Behaviorally, the color singleton distractor generally reduced the reaction time (RT). This RT benefit (ΔRT) was higher in the high-WMC group relative to the low-WMC group, indicating the superior distractor suppression ability of the high-WMC group. Moreover, leveraging voxel-based morphometry analysis, gray matter morphology (volume and deformation) in the ventral attention network (VAN) was found to show the same, positive associations with ΔRT in both WMC groups. However, correlations of the opposite sign were found between ΔRT and gray matter morphology in the frontoparietal (FPN)/default mode network (DMN) in the two WMC groups. Furthermore, resting-state functional connectivity analysis centering on regions with a structural-behavioral relationship found that connections between the left orbital and right superior frontal gyrus (hubs of DMN and VAN, respectively) was correlated with ΔRT in the high-WMC group (but not in the low-WMC group). Collectively, our work present shared and distinct neuroanatomical substrates of distractor suppression in high- and low-WMC individuals. Furthermore, intrinsic connectivity of the brain network hubs in high-WMC individuals may account for their superior ability in suppressing salient distractors. [ABSTRACT FROM AUTHOR]

Selective attention, the ability to filter relevant from a sea of sensory information, relies on the prioritization of goal-relevant information (target facilitation) and the suppression of goal-irrelevant information (distractor suppression). Although several lines of evidence have shown that target facilitation and distractor suppression were mediated by distinct mechanisms, the underlying neural substrates remain unclear. To address this question, we acquired structural and resting-state magnetic resonance imaging scans, as well as behavioral data from a modified Posner cueing task. Specifically, the location of a target (Target Cue, TC) and a distractor (Distractor Cue, DC) was either cued in advance to separately trigger target facilitation and distractor suppression, or no predictive information was provided, serving as a baseline. We combined voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analyses to explore the neural correlates of behavioral benefits, yielding the following results. First, behavioral data showed faster responses to TC and DC conditions compared to baseline, the benefits of which were named TC-benefit and DC-benefit. Second, the VBM analysis revealed that the gray matter volume (GMV) in the superior frontal (SFG) and postcentral gyrus inversely correlated with individual TC-benefit, while the GMV in the superior parietal lobe, middle frontal gyrus, and angular gyrus inversely correlated with individual DC-benefit, indicating that target facilitation and distractor suppression was associated with the GMV of distinct and distributed regions in the frontoparietal cortex. Third, the rsFC analysis with the SFG as a seed region further found distinct patterns of rsFC for target facilitation and distractor suppression. Specifically, individual TC-benefit were positively correlated with distributed connections between the SFG and brain regions, mainly within the ventral attention and somato-motor network; but individual DC-benefit were positively correlated with centralized connections between the SFG and brain regions, mainly within the frontoparietal, dorsal attention and ventral attention network. Finally, a multiple linear regression analysis showed that the GMV and rsFC could jointly explain individual differences in TC- and DC-benefit. Taken together, these results provided neural evidence for different structural and functional substrates underlying target facilitation and distractor suppression. ∙ Location cue of a distractor or target quickened search responses (DC/TC-benefit). ∙Neural substrates of DC/TC-benefit were explored using VBM and rsFC analyses. ∙Both GMV and rsFC analysis revealed distinct neural correlates of DC/TC-benefit. ∙GMV and rsFC together explained over 80% of individual variations in DC/TC-benefit. [ABSTRACT FROM AUTHOR]

As the aging population increases, the focus on elderly patients with acute respiratory distress syndrome (ARDS) is also increasing. In this article, we found progranulin (PGRN) differential expression in ARDS patients and healthy controls, even in young and old ARDS patients. Its expression strongly correlates with several cytokines in both young and elderly ARDS patients. PGRN has comparable therapeutic effects in young and elderly mice with lipopolysaccharide-induced acute lung injury, manifesting as lung injury, apoptosis, inflammation, and regulatory T cells (Tregs) differentiation. Considering that Tregs differentiation relies on metabolic reprogramming, we discovered that Tregs differentiation was mediated by mitochondrial function, especially in the aged population. Furthermore, we demonstrated that PGRN alleviated the mitochondrial damage during Tregs differentiation through the AMPK/PGC-1α pathway in T cells. Collectively, PGRN may regulate mitochondria function to promote Tregs differentiation through the AMPK/PGC-1α pathway to improve ARDS. [Display omitted] • Differential expression of PGRN and mitochondrial respiratory in ARDS patients and healthy controls. • PGRN has an equivalent therapeutic effect on Tregs differentiation in young and old ALI mice induced by LPS intratracheal instillation. • PGRN has a better promotion effect on metabolic reprogramming during the differentiation of old Tregs than that of young. • PGRN promotes mitochondrial function through the AMPK/PGC-1α pathway in T cells. [ABSTRACT FROM AUTHOR]

• Distractor suppression (DS) was measured using visual search task. • Using functional connectivity between large anatomical regions to predict DS. • Prefrontal-temporal, insula-limbic, parietal-occipital connections were key to DS. • The model could also predict daily distractibility in an independent sample. Distractor suppression (DS) is crucial in goal-oriented behaviors, referring to the ability to suppress irrelevant information. Current evidence points to the prefrontal cortex as an origin region of DS, while subcortical, occipital, and temporal regions are also implicated. The present study aimed to examine the contribution of communications between these brain regions to visual DS. To do it, we recruited two independent cohorts of participants for the study. One cohort participated in a visual search experiment where a salient distractor triggering distractor suppression to measure their DS and the other cohort filled out a Cognitive Failure Questionnaire to assess distractibility in daily life. Both cohorts collected resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate function connectivity (FC) underlying DS. First, we generated predictive models of the DS measured in visual search task using resting-state functional connectivity between large anatomical regions. It turned out that the models could successfully predict individual's DS, indicated by a significant correlation between the actual and predicted DS (r = 0.32, p < 0.01). Importantly, Prefrontal-Temporal, Insula-Limbic and Parietal-Occipital connections contributed to the prediction model. Furthermore, the model could also predict individual's daily distractibility in the other independent cohort (r = –0.34, p < 0.05). Our findings showed the efficiency of the predictive models of distractor suppression encompassing connections between large anatomical regions and highlighted the importance of the communications between attention-related and visual information processing regions in distractor suppression. Current findings may potentially provide neurobiological markers of visual distractor suppression. [ABSTRACT FROM AUTHOR]

Abstract: The anti-inflammatory activity of the predominant procyanidin dimer in cocoa, dimer B2, was investigated in this study. Pretreatment of the procyanidin dimer B2 reduced COX-2 expression induced by the endotoxin lipopolysaccharide (LPS) in differentiated human monocytic cells (THP-1) in culture. To further elucidate the underlying mechanism of COX-2 inhibition by procyanidin, we examined their effects on the activation of extracellular signal-regulated protein kinase (ERK), Jun-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), which are upstream enzymes known to regulate COX-2 expression in many cell types. Pretreatment with procyanidin dimer B2 decreased the activation of ERK, JNK, and p38 MAPK. In addition, procyanidin dimer B2 suppressed the NF-κB activation through stabilization of IκB proteins, suggesting that these signal-transducing enzymes could be potential targets for procyanidin dimer B2. By affecting the expression rather than the activity of COX-2, these in vitro data reported herein give further evidence on the anti-inflammatory protection by procyanidins. [Copyright &y& Elsevier]

Abstract: Calcium-dependent mechanisms, particularly those mediated by Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII), have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H in cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50 mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation status and PRs. [Copyright &y& Elsevier]