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  • Neuroinformatics
  • 2023-2023
  • Open Access
  • CN

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Qihao Zhang; Chaofan Sui; Junghun Cho; Linfeng Yang; +6 Authors

    The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia.Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups.Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (allUsing whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Korean Journal of Ra...arrow_drop_down
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    Korean Journal of Radiology
    Article . 2023 . Peer-reviewed
    License: CC BY NC
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Korean Journal of Ra...arrow_drop_down
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      Korean Journal of Radiology
      Article . 2023 . Peer-reviewed
      License: CC BY NC
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    Authors: Ke Li; Huiying Gong; Jinyu Qiu; Ruimin Li; +3 Authors

    A patch clamp is the “gold standard” method for studying ion-channel biophysics and pharmacology. Due to the complexity of the operation and the heavy reliance on experimenter experience, more and more researchers are focusing on patch-clamp automation. The existing automated patch-clamp system focuses on the process of completing the experiment; the detection method in each step is relatively simple, and the robustness of the complex brain film environment is lacking, which will increase the detection error in the microscopic environment, affecting the success rate of the automated patch clamp. To address these problems, we propose a method that is suitable for the contact between pipette tips and neuronal cells in automated patch-clamp systems. It mainly includes two key steps: precise positioning of pipettes and contact judgment. First, to obtain the precise coordinates of the tip of the pipette, we use the Mixture of Gaussian (MOG) algorithm for motion detection to focus on the tip area under the microscope. We use the object detection model to eliminate the encirclement frame of the pipette tip to reduce the influence of different shaped tips, and then use the sweeping line algorithm to accurately locate the pipette tip. We also use the object detection model to obtain a three-dimensional bounding frame of neuronal cells. When the microscope focuses on the maximum plane of the cell, which is the height in the middle of the enclosing frame, we detect the focus of the tip of the pipette to determine whether the contact between the tip and the cell is successful, because the cell and the pipette will be at the same height at this time. We propose a multitasking network CU-net that can judge the focus of pipette tips in complex contexts. Finally, we design an automated contact sensing process in combination with resistance constraints and apply it to our automated patch-clamp system. The experimental results show that our method can increase the success rate of pipette contact with cells in patch-clamp experiments.

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    Sensors
    Article . 2023 . Peer-reviewed
    License: CC BY
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    Sensors
    Article . 2023
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Sensorsarrow_drop_down
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      Sensors
      Article . 2023 . Peer-reviewed
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      Sensors
      Article . 2023
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Yiyang, Li; Bowen, Liu; Tingting, Zhao; Xingping, Quan; +6 Authors

    Abstract Background Blood–brain barrier (BBB) disruption is a major adverse event after ischemic stroke (IS). Caveolin-1 (Cav-1), a scaffolding protein, played multiple roles in BBB permeability after IS, while the pros and cons of Cav-1 on BBB permeability remain controversial. Numerous studies revealed that extracellular vesicles (EVs), especially stem cells derived EVs, exerted therapeutic efficacy on IS; however, the mechanisms of BBB permeability needed to be clearly illustrated. Herein, we compared the protective efficacy on BBB integrity between bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and EVs from brain endothelial cells (BEC-EVs) after acute IS and investigated whether the mechanism was associated with EVs antagonizing Cav-1-dependent tight junction proteins endocytosis. Methods BMSC-EVs and BEC-EVs were isolated and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscope. Oxygen and glucose deprivation (OGD) treated b. End3 cells were utilized to evaluate brain endothelial cell leakage. CCK-8 and TRITC-dextran leakage assays were used to measure cell viability and transwell monolayer permeability. Permanent middle cerebral artery occlusion (pMCAo) model was established, and EVs were intravenously administered in rats. Animal neurological function tests were applied, and microvessels were isolated from the ischemic cortex. BBB leakage and tight junction proteins were analyzed by Evans Blue (EB) staining and western blotting, respectively. Co-IP assay and Cav-1 siRNA/pcDNA 3.1 vector transfection were employed to verify the endocytosis efficacy of Cav-1 on tight junction proteins. Results Both kinds of EVs exerted similar efficacies in reducing the cerebral infarction volume and BBB leakage and enhancing the expressions of ZO-1 and Claudin-5 after 24 h pMCAo in rats. At the same time, BMSC-EVs were outstanding in ameliorating neurological function. Simultaneously, both EVs treatments suppressed the highly expressed Cav-1 in OGD-exposed b. End3 cells and ischemic cerebral microvessels, and this efficacy was more prominent after BMSC-EVs administration. Cav-1 knockdown reduced OGD-treated b. End3 cells monolayer permeability and recovered ZO-1 and Claudin-5 expressions, whereas Cav-1 overexpression aggravated permeability and enhanced the colocalization of Cav-1 with ZO-1 and Claudin-5. Furthermore, Cav-1 overexpression partly reversed the lower cell leakage by BMSC-EVs and BEC-EVs administrations in OGD-treated b. End3 cells. Conclusions Our results demonstrated that Cav-1 aggravated BBB permeability in acute ischemic stroke, and BMSC-EVs exerted similar antagonistic efficacy to BEC-EVs on Cav-1-dependent ZO-1 and Claudin-5 endocytosis. BMSC-EVs treatment was superior in Cav-1 suppression and neurological function amelioration. Graphical Abstract

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    Journal of Nanobiotechnology
    Article . 2023 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Journal of Nanobiote...arrow_drop_down
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      Journal of Nanobiotechnology
      Article . 2023 . Peer-reviewed
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    Authors: Jianlin Guo; Yuanyuan Chen; Wen Liu; Lijuan Huang; +5 Authors

    AbstractBackgroundGrowing evidences have indicated neurodevelopmental disorders in infantile esotropia (IE). However, few studies have analyzed the characteristics of large‐scale functional networks of IE patients or their postoperative network‐level alterations.MethodsHere, individuals with IE (n = 32) and healthy subjects (n = 30) accomplished the baseline clinical examinations and resting‐state MRI scans. A total of 17 IE patients also underwent corrective surgeries and completed the longitudinal clinical assessments and resting‐state MRI scans. Linear mixed effects models were applied for cross‐sectional and longitudinal network‐level analyses. Correlation analysis was performed to assess the relationship between longitudinal functional connectivity (FC) alterations and baseline clinical variables.ResultsIn cross‐sectional analyses, network‐level FC were apparently aberrant in IE patients compared to controls. In longitudinal analyses, intra‐ and internetwork connectivity were observed with significant alterations in postoperative IE patients compared to the preoperative counterparts. Longitudinal FC changes are negatively correlated to the age at surgery in IE.ConclusionsObviously, altered network‐level FC benefiting from the corrective surgery serves as the neurobiological substrate of the observed improvement of stereovision, visuomotor coordination, and emotional management in postoperative IE patients. Corrective surgery should be performed as early as possible to obtain more benefits for IE in brain function recovery.

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    Brain and Behavior
    Article . 2023 . Peer-reviewed
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      Brain and Behavior
      Article . 2023 . Peer-reviewed
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    Authors: Qian, Yun; Tang, Bo; Zhang, Hao; Yang, Hui;

    Stroke is an acute cerebrovascular disease that is now the most important cause of death due to brain problems in our country. CircRNAs are RNA circles that have been extensively involved in the disease. We aimed to investigate the mechanism of circ_0129657 in the pathogenesis of stroke. In this study, quantitative real-time polymerase chain reaction (RT-qPCR) and western blot assays were used to assess the expression of circ_0129657, miR-194-5p, and glia maturation factor beta (GMFB). Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. 5-Ethynyl-2′-Deoxyuridine (EdU) assay was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to assess the relationship between miR-194-5p and circ_0129657 or GMFB. Mouse middle cerebral artery occlusion (MCAO) model was applied to mimic the cerebral ischemia/reperfusion injury. Our data showed that the levels of circ_0129657 and GMFB were significantly increased and the expression of miR-194-5p was significantly decreased in oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs). Silencing circ_0129657 expression in OGD-induced HBMECs could promote cell viability and cell proliferation. Moreover, circ_0129657 depletion also could inhibit apoptosis and inflammatory factor secretion. Circ_0129657 functioned as a sponge for miR-194-5p and could regulate GMFB expression via miR-194-5p competition. Furthermore, miR-194-5p downregulation or GMFB restoration could partially reverse the effects of circ_0129657 silencing on cell biological properties in OGD-induced HBMECs. Meanwhile, circ_0129657 knockdown decreased cerebral infarction volume and neurological impairment in MCAO mouse models. In conclusion, our findings suggest that circ_0129657 can inhibit cell proliferation and promote apoptosis and inflammatory factor secretion in HBMECs after oxygen-glucose deprivation via miR-194-5p/GMFB axis, providing evidence that circ_0129657 has the potential as a useful biological molecular marker in the diagnosis of stroke.

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    Autoimmunity
    Article . 2023 . Peer-reviewed
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      Autoimmunity
      Article . 2023 . Peer-reviewed
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    Authors: Yue Chen; Liqian Cui; Hao Li; Aili Gao;

    AbstractBackgroundStructural abnormalities in the brain of patients with atopic dermatitis (AD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of AD on brain structure.MethodsThis study utilized summary statistics from genome‐wide association studies (GWASs) to investigate a collection of cerebral structural measures, encompassing cortical thickness (CT), cortical surface area (CA), and subcortical volumes in T1 images. A comprehensive GWAS meta‐analysis identified a total of 20 independent single nucleotide polymorphisms linked to AD, surpassing the genome‐wide significance threshold (p < 5 × 10⁻⁸). MR estimates were aggregated through the application of the inverse variance weighted method. Additional complementary analyses (i.e., MR‐Egger and weighted median approaches) were conducted to further assess the robustness of the obtained results. Sensitivity analysis and multivariate MR (MVMR) while adjusting for brain structural changes risk factors (i.e., depression and anxiety) were performed to assess the reliability and stability of observed causality.ResultsGenetically determined AD exhibited a causal link with reduced caudate volumes (IVW‐MR: β = ‐0.186, p = 0.001, p‐corrected = 0.009). Furthermore, we identified potential causal associations between AD and reduced CT in the cingulate region (posterior cingulate, IVW‐MR: β = ‐0.065, p = 0.018, p‐corrected = 0.551; isthmus cingulate, IVW‐MR: β = ‐0.086, p = 0.003, p‐corrected = 0.188), as well as abnormal cortical surface area (CA) in the supramarginal (IVW‐MR: β = ‐0.047, p = 0.044, p‐corrected = 0.714) and isthmus cingulate (IVW‐MR: β = 0.053, p = 0.018, p‐corrected = 0.714). Additional supplementary analyses yielded consistent outcomes. There was no evidence of horizontal pleiotropy. MVMR analysis showed that the causal effects of AD on abnormal brain structure remained significant while adjusting for depression and anxiety.ConclusionThis MR study provided suggestive evidence that decreased caudate nucleus, posterior cingulate cortex, isthmus cingulate cortex and supramarginal gyrus are suggestively associated with higher AD risk. Future investigation into the brain regions is recommended, which helps to clarify the underlying mechanisms and point to new therapies against AD.

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    Radboud Repository
    Article . 2023
    Data sources: Radboud Repository
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    Skin Research and Technology
    Article . 2023 . Peer-reviewed
    License: CC BY
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      Radboud Repository
      Article . 2023
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      Skin Research and Technology
      Article . 2023 . Peer-reviewed
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    Authors: Yingyao, He; Xinyue, Wang; Kelong, Lu; Ning, Hao;

    AbstractThis study aimed to investigate how the ways leaders arise (appointed vs. emergent) affect the leader–follower interaction during creative group communication. Hyperscanning technique was adopted to reveal the underlying interpersonal neural correlates using functional near-infrared spectroscopy. Participants were assigned into 3-person groups to complete a creative problem-solving task. These groups were randomly split into conditions of appointed (condition A) and emergent (condition E) leaders. Creative group outcomes were better in condition E, accompanied by more frequent perspective-taking behaviors between leaders and followers. The interpersonal brain synchronization (IBS) increment for leader–follower pairs was significantly higher at the right angular gyrus (rAG), between the rAG and the right supramarginal gyrus (rSMG), and between the right middle temporal gyrus and the right motor cortex in condition E and positively correlated with perspective-taking behaviors between leaders and followers. The graph-based analysis showed higher nodal betweenness of the rAG and the rSMG in condition E. These results indicated the neural coupling of brain regions involved in mentalizing, semantic processing and motor imagery may underlie the dynamic information transmission between leaders and followers during creative group communication.

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    Cerebral Cortex
    Article . 2023 . Peer-reviewed
    License: OUP Standard Publication Reuse
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    Cerebral Cortex
    Article . 2022
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      Cerebral Cortex
      Article . 2023 . Peer-reviewed
      License: OUP Standard Publication Reuse
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      Cerebral Cortex
      Article . 2022
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    Authors: Jianjian Cai; Jia Li; Dong Liu; Sikang Gao; +3 Authors

    AbstractIntroductionChildhood trauma is prevalent in our society, whereas little is known about why and how different forms of early traumatic experiences exert long‐term effects on differential brain function in adulthood.PurposeThis study aimed to scale experience‐specific neural correlates of distinct subtypes of childhood trauma.MethodsWe used resting‐state functional magnetic resonance imaging data from 216 adults with different degrees of childhood trauma. Graph analysis was combined with the Childhood Trauma Questionnaire to inspect the impact of distinct subtypes of childhood trauma on the brain.ResultsWe found that childhood trauma experiences have a detrimental effect on depression and anxiety behavior. On one hand, childhood neglect scores were positively associated with network transmission efficiency of regions involved in cognitive and executive functions, such as temporal lobe, insular cortex, and parahippocampal gyrus. On the other hand, childhood abuse scores were tightly linked to functional reorganizations of regions mediated by immature ego defense system and damaged emotion representation. Specifically, the abuse scores were positively associated with network transmission efficiency of the visual, auditory, linguistic, and motor cortex. Isolated communications in temporal cortex and supplementary motor cortex were related to emotional and physical abuse scores.ConclusionsOur data showed the differential associations of abusive and neglectful experiences with brain function in adulthood. These experience‐specific associations could underpin potentially differential risks of specific forms of psychiatric sequelae in adulthood. More attentions to maltreated children and timely psychological treatment are needed to reduce the incidence of psychosis.

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    Brain and Behavior
    Article . 2023 . Peer-reviewed
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      Brain and Behavior
      Article . 2023 . Peer-reviewed
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    Authors: Shudong Zhang; Jingjing Zhou; Jian Cui; Zhifang Zhang; +9 Authors

    AbstractIn this study, the effects of antidepressants on large‐scale brain networks and the neural basis of individual differences in response were explored. A total of 41 patients with major depressive disorder (MDD) and 42 matched healthy controls (HCs) were scanned by resting‐state functional magnetic resonance imaging separately at baseline and after a 12‐week follow‐up. The patients with MDD received escitalopram for 12 weeks. After treatment, patients were classified into those with MDD in remission [MDDr, endpoint 17‐item Hamilton Depression Rating Scale (HAMD) total score ≤7] and those in nonremission (MDDnr). The human Brainnetome Atlas was used to define large‐scale networks and compute within‐ and between‐network resting‐state functional connectivity (rsFC). Results showed the decreased subcortical network (SCN)–ventral attention network (VAN) connectivity at baseline increased in patients with MDD after 12‐week treatment, and it was comparable with that of HCs. This change was only observed in patients with MDDr. However, the decreased within‐network rsFC in SCN and default mode network (DMN) persisted in all patients with MDD, including those with MDDr and MDDnr, after treatment. The strength of SCN–VAN connectivity at baseline was significantly negatively correlated with the reduction rate of HAMD score in all patients with MDD. Thus, SCN–VAN connectivity may be an antidepressant target associated with depressive state changes and a predictor of treatment response to serotonin reuptake inhibitors. The within‐network rsFC in SCN and DMN may reflect a trait‐like abnormality in MDD. These findings provide further insights into the mechanism of antidepressants and their individual differences in response. The trial name is “Appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement” (URL: http://www.chictr.org.cn/showproj.aspx?proj=21377; registration number: ChiCTR‐OOC‐17012566).

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    Human Brain Mapping
    Article . 2023 . Peer-reviewed
    License: CC BY NC ND
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      Human Brain Mapping
      Article . 2023 . Peer-reviewed
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    Authors: Weihao Zheng; Xiaomin Wang; Tingting Liu; Bin Hu; +1 Authors

    AbstractPreterm‐born neonates are prone to impaired neurodevelopment that may be associated with disrupted whole‐brain structural connectivity. The present study aimed to investigate the longitudinal developmental pattern of the structural network from preterm birth to term‐equivalent age (TEA), and identify how prematurity influences the network topological organization and properties of local brain regions. Multi‐shell diffusion‐weighted MRI of 28 preterm‐born scanned a short time after birth (PB‐AB) and at TEA (PB‐TEA), and 28 matched term‐born (TB) neonates in the Developing Human Connectome Project (dHCP) were used to construct structural networks through constrained spherical deconvolution tractography. Structural network development from preterm birth to TEA showed reduced shortest path length, clustering coefficient, and modularity, and more “connector” hubs linking disparate communities. Furthermore, compared with TB newborns, premature birth significantly altered the nodal properties (i.e., clustering coefficient, within‐module degree, and participation coefficient) in the limbic/paralimbic, default‐mode, and subcortical systems but not global topology at TEA, and we were able to distinguish the PB from TB neonates at TEA based on the nodal properties with 96.43% accuracy. Our findings demonstrated a topological reorganization of the structural network occurs during the perinatal period that may prioritize the optimization of global network organization to form a more efficient architecture; and local topology was more vulnerable to premature birth‐related factors than global organization of the structural network, which may underlie the impaired cognition and behavior in PB infants.

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    Human Brain Mapping
    Article . 2023 . Peer-reviewed
    License: CC BY
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      Human Brain Mapping
      Article . 2023 . Peer-reviewed
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    Authors: Qihao Zhang; Chaofan Sui; Junghun Cho; Linfeng Yang; +6 Authors

    The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia.Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups.Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (allUsing whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

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    Korean Journal of Radiology
    Article . 2023 . Peer-reviewed
    License: CC BY NC
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      Korean Journal of Radiology
      Article . 2023 . Peer-reviewed
      License: CC BY NC
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    Authors: Ke Li; Huiying Gong; Jinyu Qiu; Ruimin Li; +3 Authors

    A patch clamp is the “gold standard” method for studying ion-channel biophysics and pharmacology. Due to the complexity of the operation and the heavy reliance on experimenter experience, more and more researchers are focusing on patch-clamp automation. The existing automated patch-clamp system focuses on the process of completing the experiment; the detection method in each step is relatively simple, and the robustness of the complex brain film environment is lacking, which will increase the detection error in the microscopic environment, affecting the success rate of the automated patch clamp. To address these problems, we propose a method that is suitable for the contact between pipette tips and neuronal cells in automated patch-clamp systems. It mainly includes two key steps: precise positioning of pipettes and contact judgment. First, to obtain the precise coordinates of the tip of the pipette, we use the Mixture of Gaussian (MOG) algorithm for motion detection to focus on the tip area under the microscope. We use the object detection model to eliminate the encirclement frame of the pipette tip to reduce the influence of different shaped tips, and then use the sweeping line algorithm to accurately locate the pipette tip. We also use the object detection model to obtain a three-dimensional bounding frame of neuronal cells. When the microscope focuses on the maximum plane of the cell, which is the height in the middle of the enclosing frame, we detect the focus of the tip of the pipette to determine whether the contact between the tip and the cell is successful, because the cell and the pipette will be at the same height at this time. We propose a multitasking network CU-net that can judge the focus of pipette tips in complex contexts. Finally, we design an automated contact sensing process in combination with resistance constraints and apply it to our automated patch-clamp system. The experimental results show that our method can increase the success rate of pipette contact with cells in patch-clamp experiments.

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    Sensors
    Article . 2023 . Peer-reviewed
    License: CC BY
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    Sensors
    Article . 2023
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      Sensors
      Article . 2023 . Peer-reviewed
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      Sensors
      Article . 2023
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    Authors: Yiyang, Li; Bowen, Liu; Tingting, Zhao; Xingping, Quan; +6 Authors

    Abstract Background Blood–brain barrier (BBB) disruption is a major adverse event after ischemic stroke (IS). Caveolin-1 (Cav-1), a scaffolding protein, played multiple roles in BBB permeability after IS, while the pros and cons of Cav-1 on BBB permeability remain controversial. Numerous studies revealed that extracellular vesicles (EVs), especially stem cells derived EVs, exerted therapeutic efficacy on IS; however, the mechanisms of BBB permeability needed to be clearly illustrated. Herein, we compared the protective efficacy on BBB integrity between bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and EVs from brain endothelial cells (BEC-EVs) after acute IS and investigated whether the mechanism was associated with EVs antagonizing Cav-1-dependent tight junction proteins endocytosis. Methods BMSC-EVs and BEC-EVs were isolated and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscope. Oxygen and glucose deprivation (OGD) treated b. End3 cells were utilized to evaluate brain endothelial cell leakage. CCK-8 and TRITC-dextran leakage assays were used to measure cell viability and transwell monolayer permeability. Permanent middle cerebral artery occlusion (pMCAo) model was established, and EVs were intravenously administered in rats. Animal neurological function tests were applied, and microvessels were isolated from the ischemic cortex. BBB leakage and tight junction proteins were analyzed by Evans Blue (EB) staining and western blotting, respectively. Co-IP assay and Cav-1 siRNA/pcDNA 3.1 vector transfection were employed to verify the endocytosis efficacy of Cav-1 on tight junction proteins. Results Both kinds of EVs exerted similar efficacies in reducing the cerebral infarction volume and BBB leakage and enhancing the expressions of ZO-1 and Claudin-5 after 24 h pMCAo in rats. At the same time, BMSC-EVs were outstanding in ameliorating neurological function. Simultaneously, both EVs treatments suppressed the highly expressed Cav-1 in OGD-exposed b. End3 cells and ischemic cerebral microvessels, and this efficacy was more prominent after BMSC-EVs administration. Cav-1 knockdown reduced OGD-treated b. End3 cells monolayer permeability and recovered ZO-1 and Claudin-5 expressions, whereas Cav-1 overexpression aggravated permeability and enhanced the colocalization of Cav-1 with ZO-1 and Claudin-5. Furthermore, Cav-1 overexpression partly reversed the lower cell leakage by BMSC-EVs and BEC-EVs administrations in OGD-treated b. End3 cells. Conclusions Our results demonstrated that Cav-1 aggravated BBB permeability in acute ischemic stroke, and BMSC-EVs exerted similar antagonistic efficacy to BEC-EVs on Cav-1-dependent ZO-1 and Claudin-5 endocytosis. BMSC-EVs treatment was superior in Cav-1 suppression and neurological function amelioration. Graphical Abstract

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    Journal of Nanobiotechnology
    Article . 2023 . Peer-reviewed
    License: CC BY
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      Journal of Nanobiotechnology
      Article . 2023 . Peer-reviewed
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    Authors: Jianlin Guo; Yuanyuan Chen; Wen Liu; Lijuan Huang; +5 Authors

    AbstractBackgroundGrowing evidences have indicated neurodevelopmental disorders in infantile esotropia (IE). However, few studies have analyzed the characteristics of large‐scale functional networks of IE patients or their postoperative network‐level alterations.MethodsHere, individuals with IE (n = 32) and healthy subjects (n = 30) accomplished the baseline clinical examinations and resting‐state MRI scans. A total of 17 IE patients also underwent corrective surgeries and completed the longitudinal clinical assessments and resting‐state MRI scans. Linear mixed effects models were applied for cross‐sectional and longitudinal network‐level analyses. Correlation analysis was performed to assess the relationship between longitudinal functional connectivity (FC) alterations and baseline clinical variables.ResultsIn cross‐sectional analyses, network‐level FC were apparently aberrant in IE patients compared to controls. In longitudinal analyses, intra‐ and internetwork connectivity were observed with significant alterations in postoperative IE patients compared to the preoperative counterparts. Longitudinal FC changes are negatively correlated to the age at surgery in IE.ConclusionsObviously, altered network‐level FC benefiting from the corrective surgery serves as the neurobiological substrate of the observed improvement of stereovision, visuomotor coordination, and emotional management in postoperative IE patients. Corrective surgery should be performed as early as possible to obtain more benefits for IE in brain function recovery.

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    Brain and Behavior
    Article . 2023 . Peer-reviewed
    License: CC BY
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