ABSTRACT
The self-powered electrochemical sensor (SPES), an analytical sensing device without external power supply, is integrated with the dual function of power supply and detection performance, which lay the foundation for the development of intelligent and portable electrochemical sensing devices. Herein, a novel SPES based on a zinc-air battery was constructed for the detection of hydrogen sulfide (H2S) in the lysate of colon cancer cells. Typically, an Fe/Fe3C@graphene foam with oxygen reduction performance was used to construct SPES based on a zinc-air battery (ZAB-SPES), which brings the open-circuit voltage to 1.30 V. Among them, the poisoning effect of H2S causes the catalytic performance of the oxygen reduction catalyst to decrease, causing a significant decrease in the discharge voltage of ZAB. Based on this principle, ZAB-SPES was constructed for the detection of H2S using a digital multimeter. The proposed ZAB-SPES demonstrated good selectivity and reproducibility for detecting H2S compared to the results of the H2S-specific fluorescence probe. This strategy enriches the idea of constructing a self-powered sensor and a digital multimeter as detection devices, providing technical support for the portability of SPESs.
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BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Nomograms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Female , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/immunology , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , Retrospective Studies , Middle Aged , Aged , Lymphocyte Subsets/immunology , Adult , Lymphocyte CountABSTRACT
BACKGROUND: Major depressive disorder (MDD) is associated not only with disorders in multiple brain networks but also with frequency-specific brain activities. The abnormality of spatiotemporal networks in patients with MDD remains largely unclear. METHODS: We investigated the alterations of the global spatiotemporal network in MDD patients using a large-sample multicenter resting-state functional magnetic resonance imaging dataset. The spatiotemporal characteristics were measured by the variability of global signal (GS) and its correlation with local signals (GSCORR) at multiple frequency bands. The association between these indicators and clinical scores was further assessed. RESULTS: The GS fluctuations were reduced in patients with MDD across the full frequency range (0-0.1852 Hz). The GSCORR was also reduced in the MDD group, especially in the relatively higher frequency range (0.0728-0.1852 Hz). Interestingly, these indicators showed positive correlations with depressive scores in the MDD group and relative negative correlations in the control group. CONCLUSION: The GS and its spatiotemporal effects on local signals were weakened in patients with MDD, which may impair inter-regional synchronization and related functions. Patients with severe depression may use the compensatory mechanism to make up for the functional impairments.
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BACKGROUND: There is growing evidence that gray matter atrophy is constrained by normal brain network (or connectome) architecture in neuropsychiatric disorders. However, whether this finding holds true in individuals with depression remains unknown. In this study, we aimed to investigate the association between gray matter atrophy and normal connectome architecture at individual level in depression. METHODS: In this study, 297 patients with depression and 256 healthy controls (HCs) from two independent Chinese dataset were included: a discovery dataset (105 never-treated first-episode patients and matched 130 HCs) and a replication dataset (106 patients and matched 126 HCs). For each patient, individualized regional atrophy was assessed using normative model and brain regions whose structural connectome profiles in HCs most resembled the atrophy patterns were identified as putative epicenters using a backfoward stepwise regression analysis. RESULTS: In general, the structural connectome architecture of the identified disease epicenters significantly explained 44% (±16%) variance of gray matter atrophy. While patients with depression demonstrated tremendous interindividual variations in the number and distribution of disease epicenters, several disease epicenters with higher participation coefficient than randomly selected regions, including the hippocampus, thalamus, and medial frontal gyrus were significantly shared by depression. Other brain regions with strong structural connections to the disease epicenters exhibited greater vulnerability. In addition, the association between connectome and gray matter atrophy uncovered two distinct subgroups with different ages of onset. CONCLUSIONS: These results suggest that gray matter atrophy is constrained by structural brain connectome and elucidate the possible pathological progression in depression.
Subject(s)
Depression , Gray Matter , Humans , Gray Matter/diagnostic imaging , Gray Matter/pathology , Depression/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , AtrophyABSTRACT
Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.
Subject(s)
Acute Kidney Injury , Gastrointestinal Microbiome , Limosilactobacillus reuteri , Probiotics , Gastrointestinal Microbiome/drug effects , Limosilactobacillus reuteri/physiology , Limosilactobacillus reuteri/metabolism , Animals , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism , Mice , Lipopolysaccharides/metabolism , Male , Kidney/microbiology , Kidney/metabolism , Feces/microbiology , Disease Models, Animal , Creatinine/blood , Mice, Inbred C57BL , Apoptosis/drug effectsABSTRACT
BACKGROUND: Unidentified heart failure occurs in patients with multiple myeloma when their heart was involved. CMR with late gadolinium enhancement (LGE) and T1 mapping can identify myocardial amyloid infiltrations. PURPOSE: To explore the role of CMR with late gadolinium enhancement (LGE) and T1 mapping for detection of multiple myeloma patients'heart. MATERIAL AND METHODS: A total of 16 MM patients with above underwent CMR (3.0-T) with T1 mapping (pre-contrast and post-contrast) and LGE imaging. In addition, 26 patients with non-obstructive hypertrophic cardiomyopathy and 26 healthy volunteers were compared to age- and sex-matched healthy controls without a history of cardiac disease, diabetes mellitus, or normal in CMR. All statistical analyses were performed using the statistical software GraphPad Prism. The measurement data were represented by median (X) and single sample T test was adopted. Enumeration data were represented by examples and Chi-tested was adopted. All tests were two-sided, and P values < 0.05 were considered statistically significant. RESULTS: In MM group, LVEF was lower than healthy controls and higher than that of non-obstructive hypertrophic cardiomyopathy group, but without statistically significant difference (%: 49.1 ± 17.5 vs. 55.6 ± 10.3, 40.4 ± 15.6, all P > 0.05). Pre-contrast T1 values of MM group were obviously higher than those of healthy controls and non-obstructive hypertrophic cardiomyopathy group (ms:1462.0 ± 71.3vs. 1269.3 ± 42.3, 1324.0 ± 45.1, all P < 0.05). 16 cases (100%) in MM group all had LGE. CONCLUSION: LGE joint T1 mapping wider clinical use techniques and follow-up the patients'disease severity.
Subject(s)
Cardiomyopathy, Hypertrophic , Contrast Media , Magnetic Resonance Imaging, Cine , Multiple Myeloma , Predictive Value of Tests , Stroke Volume , Ventricular Function, Left , Humans , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/diagnosis , Male , Female , Middle Aged , Contrast Media/administration & dosage , Aged , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/physiopathology , Case-Control Studies , Myocardium/pathology , Adult , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Heart Failure/diagnosis , Heart Failure/etiologyABSTRACT
Evidence has indicated abnormalities of thalamo-cortical functional connectivity (FC) in bipolar disorder during a depressive episode (BDD) and major depressive disorder (MDD). However, the dynamic FC (dFC) within this system is poorly understood. We explored the thalamo-cortical dFC pattern by dividing thalamus into 16 subregions and combining with a sliding-window approach. Correlation analysis was performed between altered dFC variability and clinical data. Classification analysis with a linear support vector machine model was conducted. Compared with healthy controls (HCs), both patients revealed increased dFC variability between thalamus subregions with hippocampus (HIP), angular gyrus and caudate, and only BDD showed increased dFC variability of the thalamus with superior frontal gyrus (SFG), HIP, insula, middle cingulate gyrus, and postcentral gyrus. Compared with MDD and HCs, only BDD exhibited enhanced dFC variability of the thalamus with SFG and superior temporal gyrus. Furthermore, the number of depressive episodes in MDD was significantly positively associated with altered dFC variability. Finally, the disrupted dFC variability could distinguish BDD from MDD with 83.44% classification accuracy. BDD and MDD shared common disrupted dFC variability in the thalamo-limbic and striatal-thalamic circuitries, whereas BDD exhibited more extensive and broader aberrant dFC variability, which may facilitate distinguish between these 2 mood disorders.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Bipolar Disorder/diagnostic imaging , Magnetic Resonance Imaging , Prefrontal Cortex , Temporal Lobe , BrainABSTRACT
BACKGROUND: Morphometric studies demonstrated wide-ranging distribution of brain structural abnormalities in major depressive disorder (MDD). OBJECTIVE: This study explored the progressive gray matter volume (GMV) changes pattern of structural network in 108 MDD patients throughout the illness duration by using voxel-based morphometric analysis. METHODS: The causal structural covariance network method was applied to map the causal effects of GMV alterations between the original source of structural changes and other brain regions as the illness duration prolonged in MDD. This was carried out by utilizing the Granger causality analysis to T1-weighted data ranked based on the disease progression information. RESULTS: With greater illness duration, the GMV reduction was originated from the right insula and progressed to the frontal lobe, and then expanded to the occipital lobe, temporal lobe, dorsal striatum (putamen and caudate) and the cerebellum. Importantly, results revealed that the right insula was the prominent node projecting positive causal influences (i.e., GMV decrease) to frontal lobe, temporal lobe, postcentral gyrus, putamen, and precuneus. While opposite causal effects were detected from the right insula to the angular, parahippocampus, supramarginal gyrus and cerebellum. CONCLUSIONS: This work may provide further information and vital evidence showing that MDD is associated with progressive brain structural alterations.
Subject(s)
Brain Diseases , Depressive Disorder, Major , Humans , Gray Matter/diagnostic imaging , Depressive Disorder, Major/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Brain/diagnostic imaging , Frontal Lobe , Magnetic Resonance Imaging/methodsABSTRACT
The interval timing can be distorted by emotions. Previous studies indicated that anticipated fear stimuli can lead to temporal overestimation, similar to the effects observed from direct exposure to fear stimuli. However, this time distortion may not always manifest when anticipated. This study aimed to systematically examine the effect of the reinforcement probability of anticipated fear stimuli on time perception in predictable emotional scenarios. The experiment established 100% fear conditioning by associating a conditioned stimulus (CS+) with an aversive unconditioned stimulus (US), electrical stimulation. Participants completed a temporal bisection task under different cues (threat CS+ and safe CS-) expectations. Participants were explicitly informed that an aversive electrical stimulus would always follow the threat cues (CS+) with 100% probability, though in reality, different blocks presented the threat cue with probability manipulation of 50 and 100%. Results showed that only in the 50% reinforcement probability, participants overestimated the duration when anticipating aversive electrical stimulation, while no significant differences were observed in the 100% reinforcement probability. Additionally, the effect of anxiety on temporal judgment failed to capture the overall trend as fixed effects but only contributed to the individual variations as random effects. The findings suggest that the anticipated aversive electrical stimulation may lead to temporal overestimation. Furthermore, the results indicate that a reliable approach for manipulating the effect of anticipated aversive electrical stimulation on temporal overestimation is to establish 100% fear conditioning and use a reinforcement probability like 50%.
Subject(s)
Fear , Reinforcement, Psychology , Humans , Fear/psychology , Emotions , Conditioning, Classical/physiology , ProbabilityABSTRACT
Burns are a common type of trauma that seriously affect not only the physical health, but also the mental health and quality of life of the patient. Extracorporeal shock wave therapy (ESWT) is an emerging treatment that has been used in clinical treatment. It has many advantages, including safety, non-invasiveness, efficiency, short treatment duration, fewer complications, and relatively low prices. In clinical settings, ESWT has played an important role in the healing process of burns and the prevention of sequelae. This article reviews the history of ESWT, the mechanism of ESWT to promote burn healing, and the application of ESWT in burns. Current status of ESWT treatment for burns as well as future perspectives for research have been summarized and proposed. However, patients with burns cannot be considered recovered when the wounds have healed, we need some new technology to adjust to the challenges of the future.
Subject(s)
Burns , Extracorporeal Shockwave Therapy , Humans , Quality of Life , Wound Healing , Burns/complications , Burns/therapy , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200-CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. METHODS: The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. RESULTS: We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. CONCLUSIONS: Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.
Subject(s)
Brain-Derived Neurotrophic Factor , Microglia , Animals , Mice , Hippocampus , Neurogenesis , Dentate GyrusABSTRACT
Major depressive disorder (MDD) is a chronic and highly recurrent disorder. The functional connectivity in depression is affected by the cumulative effect of course of illness. However, previous neuroimaging studies on abnormal functional connection have not mainly focused on the disease duration, which is seen as a secondary factor. Here, we used a data-driven analysis (multivariate distance matrix regression) to examine the relationship between the course of illness and resting-state functional dysconnectivity in MDD. This method identified a region in the anterior cingulate cortex, which is most linked to course of illness. Specifically, follow-up seed analyses show this phenomenon resulted from the individual differences in the topological distribution of three networks. In individuals with short-duration MDD, the connection to the default mode network was strong. By contrast, individuals with long-duration MDD showed hyperconnectivity to the ventral attention network and the frontoparietal network. These results emphasized the centrality of the anterior cingulate cortex in the pathophysiology of the increased course of illness and implied critical links between network topography and pathological duration. Thus, dissociable patterns of connectivity of the anterior cingulate cortex is an important dimension feature of the disease process of depression.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Neural Pathways/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Gyrus Cinguli/diagnostic imaging , Brain MappingABSTRACT
BACKGROUND: Problematic smartphone use (PSU) is adversely correlated with resilience. To completely comprehend the mechanism underlying this relationship, however, more investigation is required. METHODS: For this cross-sectional study, the method of stratified random cluster sampling was applied. 834 Chinese undergraduate students (aged 17 to 24) were recruited, and self-reported questionnaires were administered to measure their levels of resilience, perceived social support, the sense of school belonging, and habitual and problematic smartphone use. RESULTS: The findings showed that resilience both directly and indirectly predicted PSU through perceived social support and the sense of school belonging. Additionally, there were significant moderating effects of habitual smartphone use between resilience and perceived social support, the sense of school belonging, and PSU. CONCLUSIONS: Our research identified the negative influence of resilience on PSU, and specifically, highlighted the mediation effects of perceived social support and the sense of school belonging. Of significance, we also found the moderation effect of habitual smartphone use in the development of PSU.
Subject(s)
Behavior, Addictive , Humans , Smartphone , Cross-Sectional Studies , Students , Surveys and QuestionnairesABSTRACT
BACKGROUND: The main types of PD-L1 in the blood include soluble PD-L1 (sPD-L1), exosomal PD-L1 (exoPD-L1), and PD-L1 in circulating tumor cells (CTCs). However, the predictive and prognostic values of these three indicators in patients with non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy are unclear, warranting a systematic meta-analysis. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) values were extracted from the included studies to investigate the correlation between the three PD-L1 indicators and overall survival (OS) or progression-free survival (PFS). The Newcastle-Ottawa Scale (NOS) was used to examine the quality of the included studies. Subgroup analyses were employed to investigate the heterogeneity. The publication bias of the included studies was assessed using Begg's and Egger's tests. P < 0.05 was regarded as significantly different. RESULTS: The pooled results revealed that high pre-treatment sPD-L1 levels were significantly associated with inferior OS (HR = 2.32, 95% CI = 1.68-3.18, P < 0.001) and PFS (HR = 2.52, 95% CI = 1.72-3.68, P < 0.001). However, dynamic changes in sPD-L1 after immunotherapy were not statistically significant for OS (HR = 1.46, 95% CI = 0.65-3.26, P > 0.05) or PFS (HR = 1.62, 95% CI = 0.92-2.86, P > 0.05). Meanwhile, the upregulated pre-treatment exoPD-L1 levels were significantly associated with poor PFS (HR = 4.44, 95% CI = 2.87-6.89, P < 0.001), whereas the post-treatment dynamic upregulation of exoPD-L1 was significantly correlated with superior PFS (HR = 0.36, 95% CI = 0.24-0.54, P < 0.001) and OS (HR = 0.20, 95% CI = 0.07-0.53, P < 0.001). For PD-L1 in CTCs, the pooled results indicated that PD-L1 expression in CTCs was not significantly correlated with OS (HR = 0.75, 95% CI = 0.49-1.13, P = 0.170) and PFS (HR = 0.79, 95% CI = 0.59-1.06, P = 0.12). CONCLUSIONS: Blood-based PD-L1 analysis is a potential strategy for predicting treatment efficacy and prognosis in patients with cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Prognosis , Lung Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , B7-H1 Antigen , Biomarkers, Tumor/metabolismABSTRACT
N-doped carbon Co/CoOx with laccase-like activity was directionally designed by pyrolyzing Co-coordination polymer and applied to detect epinephrine, which revealed a new preparation strategy for laccase mimics. The formation mechanism of the N-doped carbon Co/CoOx nanozyme was reconnoitered by a thermogravimetric-mass spectrometry system (TG-MS). N-doped carbon Co/CoOx exhibited outstanding laccase-like activity, and the Michaelis-Menten constant and maximum initial velocity were calculated to be 0.087 mM and 0.0089 µM s-1, respectively. Based on this principle, a simple colorimetric sensing platform was developed for the quantitative detection of epinephrine, which can be used to diagnose pheochromocytoma. In addition, the visual platform for detecting epinephrine exhibited a linear range of 3 to 20 µg mL-1 and a calculated detection limit of 0.42 µg mL-1. Therefore, the proposed colorimetric sensing platform is a promising candidate to be applied in precise early pheochromocytoma diagnosis.
Subject(s)
Adrenal Gland Neoplasms , Pheochromocytoma , Humans , Laccase , Carbon , EpinephrineABSTRACT
Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.
Subject(s)
Ependymoma , Adult , Child , Ependymoma/genetics , Ependymoma/pathology , Ependymoma/surgery , Humans , Mutation , RNA, Messenger , Receptors, G-Protein-Coupled/genetics , Young AdultABSTRACT
Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression.
Subject(s)
Adenosine Triphosphate/metabolism , Apyrase , Depressive Disorder, Major , Animals , Apyrase/genetics , Apyrase/metabolism , Depression/genetics , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Hippocampus/metabolism , Mice , Mice, Inbred C57BLABSTRACT
As the important benthic animal in coastal wetlands, crab bioturbation may signiï¬cantly affect the nitrogen (N) budgets by regulating microbial N transformation processes. However, the response of interaction between different microbial N processes to crab bioturbation remains poorly understood. Here, a 30-day microcosmic experiment was conducted using sediment collected from the Yangtze Estuary wetland, followed by the determination of temporal variations of physicochemical parameters, N removal (denitrification plus anammox, which is defined as N2 production) and retention rates (nitrate dissimilatory reduction to ammonium, DNRA) as well as relevant gene abundances in response to different crabs densities. The results showed that crab bioturbation simultaneously promoted the rates of N2 production and DNRA processes. These two process rates were positively associated with the intensity of crab bioturbation, which was supported by molecular analysis of relevant functional gene abundance. Crab bioturbation was more beneficial to DNRA than N2 production. Due to this disproportionate stimulation, crab bioturbation increased the importance of DNRA, indicating that N retention was becoming more significant under crab bioturbation in estuarine and coastal wetlands. The variations of sediment total organic carbon and oxygen availability driven by crab bioturbation were the critical factors mediating the changes in microbial N removal and retention. Overall, our findings highlighted that crab bioturbation can affect the N budgets in estuarine and coastal wetlands by altering the competition between microbial N removal and retention.
Subject(s)
Ammonium Compounds , Brachyura , Animals , Carbon , Denitrification , Nitrates/analysis , Nitrogen/analysis , Oxygen , WetlandsABSTRACT
The dynamic architecture of the human brain has been consistently observed. However, there is still limited modeling work to elucidate how neuronal circuits are hierarchically and flexibly organized in functional systems. Here we proposed a reachable probability approach based on non-homogeneous Markov chains, to characterize all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level. We proved at the theoretical level the convergence of the functional brain network system, and demonstrated that this approach is able to detect network steady states across connectivity structure, particularly in areas of the default mode network. We further explored the dynamically hierarchical functional organization centered at the primary sensory cortices. We observed smaller optimal reachable steps to their local functional regions, and differentiated patterns in larger optimal reachable steps for primary perceptual modalities. The reachable paths with the largest and second largest transition probabilities between primary sensory seeds via multisensory integration regions were also tracked to explore the flexibility and plasticity of the multisensory integration. The present work provides a novel approach to depict both the stable and flexible hierarchical connectivity organization of the human brain.
Subject(s)
Brain/physiology , Nerve Net/physiology , Adolescent , Adult , Connectome/methods , Female , Humans , Magnetic Resonance Imaging , Male , Markov Chains , Middle Aged , Probability , Spatio-Temporal Analysis , Young AdultABSTRACT
Blood components are considered to reflect nutrient metabolism and immune activity in both humans and animals. In this study, we measured 12 blood components in Pekin ducks and performed genome-wide association analysis to identify the QTLs (quantitative trait locus) using a genotyping-by-sequencing strategy. A total of 54 QTLs were identified for blood components. One genome-wide significant QTL for alkaline phosphatase was identified within the intron-region of the OTOG gene (Pâ¯=â¯1.31E-07). Moreover, 21 genome-wide significant SNPs for the level of serum cholinesterase were identified on six different scaffolds. In addition, for serum calcium, one genome-wide significant QTL was identified in the upstream region of gene RAB11B. These results provide new markers for functional studies in Pekin ducks, and several candidate genes were identified, which may provide additional insights into specific mechanisms for blood metabolism in ducks and their potential application for duck breeding programs.