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.

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.

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.

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.

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.

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.

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.

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.

Single cell RNA-sequencing analysis reveals that N-acetylcysteine partially reverses hepatic immune dysfunction in biliary atresia.

Background & Aims: Our previous study indicated that CD177+ neutrophil activation has a vital role in the pathogenesis of biliary atresia (BA), which is partially ameliorated by N-acetylcysteine (NAC) treatment. Here, we evaluated the clinical efficacy of NAC treatment and profiled liver-resident immune cells via single cell RNA-sequencing (scRNA-seq) analysis to provide a comprehensive immune landscape of NAC-derived immune regulation. Methods: A pilot clinical study was conducted to evaluate the potential effects of intravenous NAC treatment on infants with BA, and a 3-month follow-up was carried out to assess treatment efficacy. scRNA-seq analysis of liver CD45+ immune cells in the control (n = 4), BA (n = 6), and BA + NAC (n = 6) groups was performed and the effects on innate cells, including neutrophil and monocyte-macrophage subsets, and lymphoid cells were evaluated. Results: Intravenous NAC treatment demonstrated beneficial efficacy for infants with BA by improving bilirubin metabolism and bile acid flow. Two hepatic neutrophil subsets of innate cells were identified by scRNA-seq analysis. NAC treatment suppressed oxidative phosphorylation and reactive oxygen species production in immature neutrophils, which were transcriptionally and functionally similar to CD177+ neutrophils. We also observed the suppression of hepatic monocyte-mediated inflammation, decreased levels of oxidative phosphorylation, and M1 polarisation in Kupffer-like macrophages by NAC. In lymphoid cells, enhancement of humoral immune responses and attenuation of cellular immune responses were observed after NAC treatment. Moreover, cell-cell interaction analysis showed that innate/adaptive proinflammatory responses were downregulated by NAC. Conclusions: Our clinical and scRNA-seq data demonstrated that intravenous NAC treatment partially reversed liver immune dysfunction, alleviated the proinflammatory responses in BA by targeting innate cells, and exhibited beneficial clinical efficacy. Impact and implications: BA is a serious liver disease that affects newborns and has no effective drug treatment. In this study, scRNA-seq showed that NAC treatment can partially reverse the immune dysfunction of neutrophil extracellular trap-releasing CD177+ neutrophils and Kupffer cells, and lower the inflammatory responses of other innate immune cells in BA. In consequence, intravenous NAC treatment improved the clinical outcomes of patients with BA in term of bilirubin metabolism.

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.

Measurement of human body parameters for human postural assessment via single camera.

We present a camera-based human body parameters measurement approach and develop a human postural assessment system. The approach combines the conventional contact measurement method and the non-contact measurement method to overcome some shortcomings in terms of time, expense, and professionalism in early methods. The entire measurement system consists of a computer, a high-definition camera, and the sticky points that are applied to the participant's body before the measurement. The camera captures the triple view image of human body. Then, the human body outline and the joint points of the human skeleton are extracted to locate the bone feature points. Finally, measurements and extractions of the human parameters are made. Experimental results demonstrate that the global postural assessment system provides quantitative guidance for human postural evaluation, and it completely changes how human postural is evaluated. The postural assessment system is significant for early diagnosis of diseases and medical rehabilitation treatment.

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.

LC-MS guided isolation of phenolic glycosides from Viburnum luzonicum Rolfe leaves and their α­amylase and α-glucosidase inhibitory activities.

Viburnum luzonicum Rolfe is widely used in China as folk medicine. The bioactivity evaluation indicated that the n-BuOH fraction of V. luzonicum leaves (VLLB) could significantly inhibit α­amylase and α-glucosidase. In order to clarify its active constituents, the phytochemical analysis on VLLB was first performed using HPLC-QTOF-MS/MS, and three new phenolic compounds, viburosides A-C (1-3), along with seven known analogues (4-10) were isolated through preparative HPLC. The undescribed compounds were determined by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ORD) and enzymatic hydrolysis. In the in vitro enzyme assays, compounds 1-8 showed potent α­amylase and α-glucosidase inhibitory activities. The enzymatic kinetics and molecular docking of the strongest inhibitors 2 and 3 against the corresponding target enzyme were also performed.

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.

Assembly of Protein Cages for Drug Delivery.

Nanoparticles (NPs) have been widely used as target delivery vehicles for therapeutic goods; however, compared with inorganic and organic nanomaterials, protein nanomaterials have better biocompatibility and can self-assemble into highly ordered cage-like structures, which are more favorable for applications in targeted drug delivery. In this review, we concentrate on the typical protein cage nanoparticles drugs encapsulation processes, such as drug fusion expression, diffusion, electrostatic contact, covalent binding, and protein cage disassembly/recombination. The usage of protein cage nanoparticles in biomedicine is also briefly discussed. These materials can be utilized to transport small molecules, peptides, siRNA, and other medications for anti-tumor, contrast, etc.

Two new phenolic allopyranosides and their analogues from the stems of Viburnum luzonicum Rolfe guided by LC-MS.

Two new phenolic allopyranosides, named viburluzosides A and B (1, 2), together with eight known phenolic glycosides (3 - 10) were discovered from the stems of Viburnum luzonicum Rolfe under the guidance of LC-MS analyses coupled with bioactivity evaluation. They were purified through various chromatography methods and identified by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, and HRESIMS) and chemical methods. The in vitro evaluation on α-glucosidase and aldose reductase (AR) inhibitory activities of isolated compounds were conducted. Compounds 1 - 4 and 6 - 9 exhibited α-glucosidase inhibitory activities with IC50 values of 5.35 - 21.34 µM and AR inhibitory activities with IC50 values of 6.21 - 40.06 µM. Moreover, the inhibitory kinetics analyses of compounds 1 and 2 were also performed.

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.

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.

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.

Aberrant functional network topology and effective connectivity in burnout syndrome.

OBJECTIVE: Recent neuroimaging studies have demonstrated that burnout is linked to specific anatomical and functional abnormalities in the brain. However, topological alterations of brain networks are not yet characterized in burnout. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 32 female participants with burnout and 30 matched healthy controls. Subsequently, we employed graph theoretical and network-based statistic (NBS) methods to analyze the functional connectivity. We further explored the causal influences between brain regions using the Granger Causal Analysis. Finally, partial correlation analyses were conducted between clinical scores and the altered network properties as well as connectivity metrics. RESULTS: Both the participants with burnout and healthy controls displayed a small-world organization. However, participants with burnout showed increased characteristic path length and decreased global efficiency. Corresponding local changes were mainly distributed in the visual network (2/3,66.67%). With the network-based statistic (NBS) approach, significantly decreased effective connectivities were observed mainly between the visual network and the right hippocampus. In addition, characteristic path length and nodal local efficiency of the left fusiform gyrus showed a significant negative correlation with depression severity. CONCLUSIONS: The present psychopathological findings reflect the disrupted global integration of the functional network related to the traits of participants with burnout. SIGNIFICANCE: These findings deliver novel insights from a full network perspective into the brain mechanisms of burnout.