Rich Club Reorganization in Nurses Before and After the Onset of Occupational Burnout: A Longitudinal MRI Study.

BACKGROUND: Studies on potential disruptions in rich club structure in nursing staff with occupational burnout are lacking. Moreover, existing studies on nurses with burnout are limited by their cross-sectional design. PURPOSE: To investigate rich club reorganization in nursing staff before and after the onset of burnout and the underlying impact of anatomical distance on such reconfiguration. STUDY TYPE: Prospective, longitudinal. POPULATION: Thirty-nine hospital nurses ( 23.67 ± 1.03 $$ 23.67\pm 1.03 $$ years old at baseline, 24.67 ± 1.03 $$ 24.67\pm 1.03 $$ years old at a follow-up within 1.5 years, 38 female). FIELD STRENGTH/SEQUENCE: Magnetization-prepared rapid gradient-echo and gradient-echo echo-planar imaging sequences at 3.0 T. ASSESSMENT: The Maslach Burnout Inventory and Symptom Check-List 90 testing were acquired at each MRI scan. Rich club structure was assessed at baseline and follow-up to determine whether longitudinal changes were related to burnout and to changes in connectivities with different anatomical distances (short-, mid-, and long range). STATISTICAL TESTS: Chi-square, paired-samples t, two-sample t, Mann-Whitney U tests, network-based statistic, Spearman correlation analysis, and partial least squares regression analysis. Significance level: Bonferroni-corrected P < 0.05 $$ P<0.05 $$ . RESULTS: In nurses who developed burnout: 1) Strengths of rich club, feeder, local, short-, mid-, and long-range connectivities were significantly decreased at follow-up compared with baseline. 2) At follow-up, strengths of above connectivities and that between A5m.R and dlPu.L were significantly correlated with emotional exhaustion (r ranges from -0.57 to -0.73) and anxiety scores (r = -0.56), respectively. 3) Longitudinal change (follow-up minus baseline) in connectivity strength between A5m.R and dlPu.L reflected change in emotional exhaustion score (r = 0.87). Longitudinal changes in strength of connectivities mainly involving parietal lobe were significantly decreased in nurses who developed burnout compared with those who did not. DATA CONCLUSION: In nurses after the onset of burnout, rich club reorganization corresponded to significant reductions in strength of connectivities with different anatomical distances. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Genome-wide identification of the SAUR gene family and screening for SmSAURs involved in root development in Salvia miltiorrhiza.

KEY MESSAGE: SmSAUR4, SmSAUR18, SmSAUR28, SmSAUR37, and SmSAUR38 were probably involved in the auxin-mediated root development in Salvia miltiorrhiza. Salvia miltiorrhiza is a widely utilized medicinal plant in China. Its roots and rhizomes are the main medicinal portions and are closely related to the quality of this herb. Previous studies have revealed that auxin plays pivotal roles in S. miltiorrhiza root development. Whether small auxin-up RNA genes (SAURs), which are crucial early auxin response genes, are involved in auxin-mediated root development in S. miltiorrhiza is worthy of investigation. In this study, 55 SmSAUR genes in S. miltiorrhiza were identified, and their physical and chemical properties, gene structure, cis-acting elements, and evolutionary relationships were analyzed. The expression levels of SmSAUR genes in different organs of S. miltiorrhiza were detected using RNA-seq combined with qRT‒PCR. The root development of S. miltiorrhiza seedlings was altered by the application of indole-3-acetic acid (IAA), and Pearson correlation coefficient analysis was conducted to screen SmSAURs that potentially participate in this physiological process. The diameter of primary lateral roots was positively correlated with SmSAUR4. The secondary lateral root number was positively correlated with SmSAUR18 and negatively correlated with SmSAUR4. The root length showed a positive correlation with SmSAUR28 and SmSAUR37 and a negative correlation with SmSAUR38. The fresh root biomass exhibited a positive correlation with SmSAUR38 and a negative correlation with SmSAUR28. The aforementioned SmSAURs were likely involved in auxin-mediated root development in S. miltiorrhiza. Our study provides a comprehensive overview of SmSAURs and provides the groundwork for elucidating the molecular mechanism underlying root morphogenesis in this species.

Age-Related Differences of Cortical Topology Across the Adult Lifespan: Evidence From a Multisite MRI Study With 1427 Individuals.

BACKGROUND: Healthy aging is usually accompanied by alterations in brain network architecture, influencing information processing and cognitive performance. However, age-associated coordination patterns of morphological networks and cognitive variation are not well understood. PURPOSE: To investigate the age-related differences of cortical topology in morphological brain networks from multiple perspectives. STUDY TYPE: Prospective, observational multisite study. POPULATION: A total of 1427 healthy participants (59.1% female, 51.75 ± 19.82 years old) from public datasets. FIELD STRENGTH/SEQUENCE: 1.5 T/3 T, T1-weighted magnetization prepared rapid gradient echo (MP-RAGE) sequence. ASSESSMENT: The multimodal parcellation atlas was used to define regions of interest (ROIs). The Jensen-Shannon divergence-based individual morphological networks were constructed by estimating the interregional similarity of cortical thickness distribution. Graph-theory based global network properties were then calculated, followed by ROI analysis (including global/nodal topological analysis and hub analysis) with statistical tests. STATISTICAL TESTS: Chi-square test, Jensen-Shannon divergence-based similarity measurement, general linear model with false discovery rate correction. Significance was set at P < 0.05. RESULTS: The clustering coefficient (q = 0.016), global efficiency (q = 0.007), and small-worldness (q = 0.006) were significantly negatively quadratic correlated with age. The group-level hubs of seven age groups were found mainly distributed in default mode network, visual network, salient network, and somatosensory motor network (the sum of these hubs' distribution in each group exceeds 55%). Further ROI-wise analysis showed significant nodal trajectories of intramodular connectivities. DATA CONCLUSION: These results demonstrated the age-associated reconfiguration of morphological networks. Specifically, network segregation/integration had an inverted U-shaped relationship with age, which indicated age-related differences in transmission efficiency. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Functional Connectome Hierarchy Distortions in Female Nurses With Occupational Burnout and Its Gene Expression Signatures.

BACKGROUND: Burnout has become a serious public health issue worldwide, particularly during the COVID-19 pandemic. Functional connectome impairments associated with occupational burnout were widely distributed, involving both low-level sensorimotor cortices and high-level association cortices. PURPOSE: To investigate whether there are hierarchical perturbations in the functional connectomes and if these perturbations are potentially influenced by genetic factors in nurses who feel "burned out." STUDY TYPE: Prospective, case control. POPULATION: Thirty-three female nurses with occupational burnout (aged 27-40, 32.42 ± 3.37) and 32 matched nurses who were not feeling burned out (aged 27-42, 32.50 ± 4.21). FIELD STRENGTH/SEQUENCE: 3.0 T, gradient-echo echo-planar imaging sequence (GE-EPI). ASSESSMENT: Gradient-based techniques were used to depict the perturbations in the multi-dimensional hierarchical structure of the macroscale connectome. Gene expression data were acquired from the Allen Human Brain Atlas. STATISTICAL TESTS: Cortex-wide multivariate analyses were used for between-group differences in gradients as well as association analyses between the hierarchy distortions and the MBI score (FDR corrected). Partial least squares, spin test and bootstrapping were utilized together to select the gene sets (FDR corrected). Gene enrichment analyses (GO, KEGG and cell-type) were further performed. Significance level: P < 0.05. RESULTS: There were significant gradient distortions, with strong between-group effects in the somatosensory network and moderate effects in the higher-order default-mode network, which were significantly correlated with the gene expression profiles (r = 0.3171). The most related genes were broadly involved in the cellular response to minerals, neuronal plasticity, and the circadian rhythm pathway (q value < 0.01). Significant enrichments were found in excitatory (r = 0.2588), inhibitory neurons (r = 0.2610), and astrocytes cells (r = 0.2633). Regions affected by burnout severity were mainly distributed in the association and visual cortices. DATA CONCLUSION: By connecting in vivo imaging to genes, cell classes, and clinical data, this study provides a framework to understand functional impairments in occupational burnout and how the microscopic genetic architecture drive macroscopic distortions. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Association of aberrant brain network dynamics with gut microbial composition uncovers disrupted brain-gut-microbiome interactions in irritable bowel syndrome: Preliminary findings.

BACKGROUND AND PURPOSE: Growing evidence suggests that abnormalities in brain-gut-microbiome (BGM) interactions are involved in the pathogenesis of irritable bowel syndrome (IBS). Our study aimed to explore alterations in dynamic functional connectivity (DFC), the gut microbiome and the bidirectional interaction in the BGM. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI), fecal samples and clinical chacteristics were collected from 33 IBS patients and 32 healthy controls. We performed a systematic DFC analysis on rs-fMRI. The gut microbiome was analyzed by 16S rRNA gene sequencing. Associations between DFC characteristics and microbial alterations were explored. RESULTS: In the DFC analysis, four dynamic functional states were identified. IBS patients exhibited increased mean dwell and fraction time in State 4, and reduced transitions from State 3 to State 1. Aberrant temporal properties in State 4 were only evident when choosing a short window (36 s or 44 s). Decreased functional connectivity (FC) variability was found in State 1 and State 3 in IBS patients, two of which (independent component [IC]51-IC91, IC46-IC11) showed significant correlations with clinical characteristics. Additionally, we identified nine significantly differential abundances in microbial composition. We also found that IBS-related microbiota were associated with aberrant FC variability, although these exploratory results were obtained at an uncorrected threshold of significance. CONCLUSIONS: Although future studies are needed to confirm our results, the findings not only provide a new insight into the dysconnectivity hypothesis in IBS from a dynamic perspective, but also establish a possible link between DFC and the gut microbiome, which lays the foundation for future research on disrupted BGM interactions.

A transformer-based multi-features fusion model for prediction of conversion in mild cognitive impairment.

Mild cognitive impairment (MCI) is usually considered the early stage of Alzheimer's disease (AD). Therefore, the accurate identification of MCI individuals with high risk in converting to AD is essential for the potential prevention and treatment of AD. Recently, the great success of deep learning has sparked interest in applying deep learning to neuroimaging field. However, deep learning techniques are prone to overfitting since available neuroimaging datasets are not sufficiently large. Therefore, we proposed a deep learning model fusing cortical features to address the issue of fusion and classification blocks. To validate the effectiveness of the proposed model, we compared seven different models on the same dataset in the literature. The results show that our proposed model outperformed the competing models in the prediction of MCI conversion with an accuracy of 83.3% in the testing dataset. Subsequently, we used deep learning to characterize the contribution of brain regions and different cortical features to MCI progression. The results revealed that the caudal anterior cingulate and pars orbitalis contributed most to the classification task, and our model pays more attention to volume features and cortical thickness features.

CD177+ cells produce neutrophil extracellular traps that promote biliary atresia.

BACKGROUND & AIMS: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA. METHODS: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed. Single-cell RNA-sequencing was performed to specifically analyse Gr-1+ (Ly6C/Ly6G+) cells in the liver. Gene expression profiles of CD177+ cells were analysed using the Smart-Seq RNA-sequencing method, and the pathogenesis of BA was examined in Cd177-/- mice. Neutrophil extracellular trap (NET) inhibitors were used to determine the role of CD177+ cell-derived NETs in BA-associated bile duct damage, and a pilot clinical study evaluated the potential effects of N-acetylcysteine on NET release in BA. RESULTS: Increased levels of Gr-1+ cells were observed in the livers of mice with rhesus rotavirus-induced BA. RNA-sequencing analysis revealed that CD177+ cells were the main population of Gr-1+ cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. Cd177-/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in CD177+ cells derived from mice with BA; these cells were associated with increased levels of reactive oxygen species and increased NET formation, which induced the apoptosis of biliary epithelial cells in cocultures. In a pilot clinical study, the administration of N-acetylcysteine to patients with BA reduced CD177+ cell numbers and reactive oxygen species levels, indicating a potential beneficial effect. CONCLUSIONS: Our data indicate that CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation. CLINICAL TRIAL REGISTRATION: The pilot study of N-acetylcysteine treatment in patients with BA was registered on the Chinese Clinical Trial Registry (ChiCTR2000040505). LAY SUMMARY: Neutrophils (a type of innate immune cell, i.e. an immune cell that doesn't target a specific antigen) are thought to play a role in the development of biliary atresia (a rare but potentially lethal condition of the bile ducts that occurs in infants). Herein, we found that neutrophils expressing a particular protein (CD177) played an important role in bile duct damage by releasing a special structure (NET) that can trap and kill pathogens but that can also cause severe tissue damage. A pilot study in patients with biliary atresia showed that inhibiting NETs could have a beneficial effect.

Altered dynamic functional connectivity in rectal cancer patients with and without chemotherapy: a resting-state fMRI study.

Purpose: Understanding the mechanism of brain functional alterations in rectal cancer (RC) patients is of great significance to improve the prognosis and quality of life of patients. Additionally, the influence of chemotherapy on brain function in RC patients is still unclear. In this study, we aimed to investigate the alterations of brain functional network dynamics in RC patients and explore the effects of chemotherapy on temporal dynamics of dynamic functional connectivity (DFC).Methods: The group independent component analysis (GICA) and sliding window method were applied to investigate abnormalities of DFC based on resting-state functional magnetic resonance imaging (rs-fMRI) of 18 RC patients without chemotherapy (RC_NC), 21 RC patients with chemotherapy (RC_C) and 33 healthy controls (HC). Then, the Spearman correlation between aberrant properties and clinical measures was calculated.Results: Two discrete states were identified. Compared to HC, RC_NC exhibited increased mean dwell time (MDT) and fractional windows (FW) in state 2 and decreased transition numbers between the two states. Notably, three temporal properties in RC_C showed an intermediate trend in comparison with RC_NC and HC. Furthermore, RC_C also demonstrated abnormal intra- and inter-network connections, involving the visual (VIS), default mode (DM), and cognitive control (CC) networks, and most connections related to VIS were correlated with the severity of anxiety and depression.Conclusions: Our study suggested that abnormal DFC patterns could be manifested in RC patients and chemotherapy would further correct abnormalities of network dynamics, which may provide new insights into the brain functional alterations in patients with RC from the time-varying connectivity perspective.

Research of Online Hand-Eye Calibration Method Based on ChArUco Board.

To solve the problem of inflexibility of offline hand-eye calibration in "eye-in-hand" modes, an online hand-eye calibration method based on the ChArUco board is proposed in this paper. Firstly, a hand-eye calibration model based on the ChArUco board is established, by analyzing the mathematical model of hand-eye calibration, and the image features of the ChArUco board. According to the advantages of the ChArUco board, with both the checkerboard and the ArUco marker, an online hand-eye calibration algorithm based on the ChArUco board is designed. Then, the online hand-eye calibration algorithm, based on the ChArUco board, is used to realize the dynamic adjustment of the hand-eye position relationship. Finally, the hand-eye calibration experiment is carried out to verify the accuracy of the hand-eye calibration based on the ChArUco board. The robustness and accuracy of the proposed method are verified by online hand-eye calibration experiments. The experimental results show that the accuracy of the online hand-eye calibration method proposed in this paper is between 0.4 mm and 0.6 mm, which is almost the same as the offline hand-eye calibration accuracy. The method in this paper utilizes the advantages of the ChArUco board to realize online hand-eye calibration, which improves the flexibility and robustness of hand-eye calibration.

Recent Advance on Chemistry and Bioactivities of Secondary Metabolites from Viburnum Plants: An Update.

Viburnum species are a group of small trees or shrubs that are of great ornamental and medicinal values. Some of them have been used for a long time both as conventional and ethnic medicine. Viburnum fruits, eaten in fresh and processed forms, have been revealed to contain various health-promoting nutrients. With the increasing research on Viburnum plants, they are considered to be an abundant resource of bioactive natural products possessing diverse pharmacological properties and unique chemical structures, that is powerfully proved by the existence of structurally novel vibsane-type diterpenoids which only occur in Viburnum species, newly discovered lignan constituents with unusual side chains and other noteworthy natural components. This review describes 185 new and 228 known secondary metabolites from Viburnum genus between 2008 and 2020, including their chemical structures, sources and bioactivities, and highlights the corresponding structure-activity relationships.

A long-wavelength ultrasensitive colorimetric fluorescent probe for carbon monoxide detection in living cells.

Exploring techniques for monitoring the intracellular signaling molecule carbon monoxide (CO) in biosystems is important to help understand its various cellular functions. Therefore, a simple long-wavelength colorimetric fluorescent probe LW-CO was designed for selectively and sensitively detecting intracellular CO in living systems. Probe LW-CO is ultrasensitive and can track CO levels in the range of 0-1 µM, with a detection limit of about 3.2 nM. Additionally, the obvious color changes of probe LW-CO with CO (yellow to pink) provide a convenient way for on-site detection of CO with the naked eye. Probe LW-CO was applied to track the exogenous levels of CO in RAW264.7 cells. Probe LW-CO proved to be an efficient method for investigating various cellular functions of CO.

Genomic analysis of PIN-FORMED genes reveals the roles of SmPIN3 in root architecture development in Salvia miltiorrhiza.

Salvia miltiorrhiza is a widely utilized medicinal herb in China. Its roots serve as crucial raw materials for multiple drugs. The root morphology is essential for the quality of this herb, but little is known about the molecular mechanism underlying the root development in S. miltiorrhiza. Previous study reveals that the polar auxin transport is critical for lateral root development in S. miltiorrhiza. Whether the auxin efflux carriers PIN-FORMEDs (PINs) are involved in this process is worthy investigation. In this study, we identified nine SmPIN genes in S. miltiorrhiza, and their chromosome localization, physico-chemical properties, and phylogenetic relationship were analyzed. SmPINs were unevenly distributed across four chromosomes, and a variety of hormone responsive elements were detected in their promoter regions. The SmPIN proteins were divided into three branches according to the phylogenetic relationship. SmPINs with close evolutionary distance showed similar conserved motif features. The nine SmPINs showed distinct tissue-specific expression patterns and most of them were auxin-inducible genes. We generated SmPIN3 overexpression S. miltiorrhiza seedlings to investigate the function of SmPIN3 in the root development in this species. The results demonstrated that SmPIN3 regulated the root morphogenesis of S. miltiorrhiza by simultaneously affecting the lateral root development and the root anatomical structure. The root morphology, patterns of root xylem and phloem as well as the expressions of genes in the auxin signaling pathway all altered in the SmPIN3 overexpression lines. Our findings provide new insights for elucidating the regulatory roles of SmPINs in the auxin-mediated root development in S. miltiorrhiza.

Automated Diagnosis of Major Depressive Disorder With Multi-Modal MRIs Based on Contrastive Learning: A Few-Shot Study.

Depression ranks among the most prevalent mood-related psychiatric disorders. Existing clinical diagnostic approaches relying on scale interviews are susceptible to individual and environmental variations. In contrast, the integration of neuroimaging techniques and computer science has provided compelling evidence for the quantitative assessment of major depressive disorder (MDD). However, one of the major challenges in computer-aided diagnosis of MDD is to automatically and effectively mine the complementary cross-modal information from limited datasets. In this study, we proposed a few-shot learning framework that integrates multi-modal MRI data based on contrastive learning. In the upstream task, it is designed to extract knowledge from heterogeneous data. Subsequently, the downstream task is dedicated to transferring the acquired knowledge to the target dataset, where a hierarchical fusion paradigm is also designed to integrate features across inter- and intra-modalities. Lastly, the proposed model was evaluated on a set of multi-modal clinical data, achieving average scores of 73.52% and 73.09% for accuracy and AUC, respectively. Our findings also reveal that the brain regions within the default mode network and cerebellum play a crucial role in the diagnosis, which provides further direction in exploring reproducible biomarkers for MDD diagnosis.

Liver fibrosis automatic diagnosis utilizing dense-fusion attention contrastive learning network.

BACKGROUND: Liver fibrosis poses a significant public health challenge given its elevated incidence and associated mortality rates. Diffusion-Weighted Imaging (DWI) serves as a non-invasive diagnostic tool for supporting the identification of liver fibrosis. Deep learning, as a computer-aided diagnostic technology, can assist in recognizing the stage of liver fibrosis by extracting abstract features from DWI images. However, gathering samples is often challenging, posing a common dilemma in previous research. Moreover, previous studies frequently overlooked the cross-comparison information and latent connections among different DWI parameters. Thus, it is becoming a challenge to identify effective DWI parameters and dig potential features from multiple categories in a dataset with limited samples. PURPOSE: A self-defined Multi-view Contrastive Learning Network is developed to automatically classify multi-parameter DWI images and explore synergies between different DWI parameters. METHODS: A Dense-fusion Attention Contrastive Learning Network (DACLN) is designed and used to recognize DWI images. Concretely, a multi-view contrastive learning framework is constructed to train and extract features from raw multi-parameter DWI. Besides, a Dense-fusion module is designed to integrate feature and output predicted labels. RESULTS: We evaluated the performance of the proposed model on a set of real clinical data and analyzed the interpretability by Grad-CAM and annotation analysis, achieving average scores of 0.8825, 0.8702, 0.8933, 0.8727, and 0.8779 for accuracy, precision, recall, specificity and F-1 score. Of note, the experimental results revealed that IVIM-f, CTRW-ß, and MONO-ADC exhibited significant recognition ability and complementarity. CONCLUSION: Our method achieves competitive accuracy in liver fibrosis diagnosis using the limited multi-parameter DWI dataset and finds three types of DWI parameters with high sensitivity for diagnosing liver fibrosis, which suggests potential directions for future research.

Fine-grained features characterize hippocampal and amygdaloid change pattern in Parkinson's disease and discriminate cognitive-deficit subtype.

AIMS: To extract vertex-wise features of the hippocampus and amygdala in Parkinson's disease (PD) with mild cognitive impairment (MCI) and normal cognition (NC) and further evaluate their discriminatory efficacy. METHODS: High-resolution 3D-T1 data were collected from 68 PD-MCI, 211 PD-NC, and 100 matched healthy controls (HC). Surface geometric features were captured using surface conformal representation, and surfaces were registered to a common template using fluid registration. The statistical tests were performed to detect differences between groups. The disease-discriminatory ability of features was also tested in the ensemble classifiers. RESULTS: The amygdala, not the hippocampus, showed significant overall differences among the groups. Compared with PD-NC, the right amygdala in MCI patients showed expansion (anterior cortical, anterior amygdaloid, and accessory basal areas) and atrophy (basolateral ventromedial area) subregions. There was notable atrophy in the right CA1 and hippocampal subiculum of PD-MCI. The accuracy of classifiers with multivariate morphometry statistics as features exceeded 85%. CONCLUSION: PD-MCI is associated with multiscale morphological changes in the amygdala, as well as subtle atrophy in the hippocampus. These novel metrics demonstrated the potential to serve as biomarkers for PD-MCI diagnosis. Overall, these findings from this study help understand the role of subcortical structures in the neuropathological mechanisms of PD cognitive impairment.

Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder. / é‡åº¦æŠ‘éƒéšœç¢æ‚£è€ ä¸˜è„‘çš®å±‚çŽ¯è·¯çš„åŠ¨æ€åŠŸèƒ½è¿žæŽ¥å¼‚å¸¸.

Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Disrupted dynamic brain functional connectivity in male cocaine use disorder: Hyperconnectivity, strongly-connected state tendency, and links to impulsivity and borderline traits.

Cocaine use is a major public health problem with serious negative consequences at both the individual and societal levels. Cocaine use disorder (CUD) is associated with cognitive and emotional impairments, often manifesting as alterations in brain functional connectivity (FC). This study employed resting-state functional magnetic resonance imaging (rs-fMRI) to examine dynamic FC in 38 male participants with CUD and 31 matched healthy controls. Using group spatial independent component analysis (group ICA) combined with sliding window approach, we identified two recurring distinct connectivity states: the strongly-connected state (state 1) and weakly-connected state (state 2). CUD patients exhibited significant increased mean dwell and fraction time in state 1, and increased transitions from state 2 to state 1, demonstrated significant strongly-connected state tendency. Our analysis revealed abnormal FC patterns that are state-dependent and state-shared in CUD patients. This study observed hyperconnectivity within the default mode network (DMN) and between DMN and other networks, which varied depending on the state. Furthermore, after adjustment for multiple comparisons, we found significant correlations between these altered dynamic FCs and clinical measures of impulsivity and borderline personality disorder. The disrupted FC and repetitive effects of precuneus and angular gyrus across correlations suggested that they might be the important hub of neural circuits related behaviorally and mentally in CUD. In summary, our study highlighted the potential of these disrupted FC as neuroimaging biomarkers and therapeutic targets, and provided new insights into the understanding of the neurophysiologic mechanisms of CUD.

Effects of second language acquisition on brain functional networks at different developmental stages.

Previous studies have shown that language acquisition influences both the structure and function of the brain. However, whether the acquisition of a second language at different periods of life alters functional network organization in different ways remains unclear. Here, functional magnetic resonance imaging data from 27 English-speaking monolingual controls and 52 Spanish-English bilingual individuals, including 22 early bilinguals who began learning a second language before the age of ten and 30 late bilinguals who started learning a second language at age fourteen or later, were collected from the OpenNeuro database. Topological metrics of resting-state functional networks, including small-world attributes, network efficiency, and rich- and diverse-club regions, that characterize functional integration and segregation of the networks were computed via a graph theoretical approach. The results showed obvious increases in network efficiency in early bilinguals and late bilinguals relative to the monolingual controls; for example, the global efficiency of late bilinguals and early bilinguals was improved relative to that of monolingual controls, and the local efficiency of early bilinguals occupied an intermediate position between that of late bilinguals and monolingual controls. Obvious increases in rich-club and diverse-club functional connectivity were observed in the bilinguals relative to the monolingual controls. Three network metrics were positively correlated with Spanish proficiency test scores. These findings demonstrated that early and late acquisition of a second language had different impacts on the functional networks of the brain.

Decreased structural pathways mediating functional connectivity in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep breathing disorder that is often accompanied by changes in structural connectivity (SC) and functional connectivity (FC). However, the current understanding of the interaction between SC and FC in OSA is still limited. METHODS: The aim of this study is to integrate complementary neuroimaging modalities into a unified framework using multi-layer network analysis methods and to reveal their complex interrelationships. We introduce a new graph metric called SC-FC bandwidth, which measures the throughput of SC mediating FC in a multi-layer network. The bandwidth differences between two groups are evaluated using the network-based statistics (NBS) method. Additionally, we traced and analyzed the SC pathways corresponding to the abnormal bandwidth. RESULTS: In both the healthy control and patients with OSA, the majority offunctionally synchronized nodes were connected via SC paths of length 2. With the NBS method, we observed significantly lower bandwidth between the right Posterior cingulate gyrus and right Cuneus, bilateral Middle frontal gyrus, bilateral Gyrus rectus in OSA patients. By tracing the high-proportion SC pathways, it was found that OSA patients typically exhibit a decrease in direct SC-FC, SC-FC triangles, and SC-FC quads intra- and inter-networks. CONCLUSION: Complex interrelationship changes have been observed between the SC and FC in patients with OSA, which might leads to abnormal information transmission and communication in the brain network.

CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein-protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14-CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.