Objectives
Depression is the most common mental complication in stroke survivors with about one‐third of patients suffering from poststroke depression (PSD). This was the first prospective study ...aimed to compare the prevalence of PSD and its symptoms between two cohorts of patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH).
Methods
Both AIS and ICH patients were simultaneously enrolled in the study. Depression symptoms were measured using the 17‐item Hamilton Depression Rating Scale (HAMD‐17) after a 1‐month follow‐up. Patients were diagnosed with PSD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition and the HAMD‐17 (HAMD scores >7).
Results
The prevalence of PSD (42.3%) in the ICH group was significantly higher than that (22.9%) in the AIS group (p < 0.001). After adjustment for conventional confounding factors, the odds ratio of PSD was 2.65 (95% CI, 1.34–5.24, p = 0.005) for ICH compared to AIS. Depressive symptoms consisting of anxiety, loss of interest, insomnia, and fatigue were more frequent in patients with ICH than in AIS patients.
Conclusions
PSD was more prevalent, and the risk was over twofold higher in patients with ICH than AIS.
Based on analysis of Epstein-Barr virus (EBV) BART microRNA expression profiles, we previously reported that EBV-encoded miR-BART13 is upregulated in nasopharyngeal carcinoma (NPC) plasma specimens. ...However, the effects and molecular mechanisms of miR-BART13 in NPC remain largely unknown. We found that miR-BART13 was significantly upregulated in NPC tissue specimens. Ectopic expression of miR-BART13 promoted NPC cell proliferation, epithelial mesenchymal transition, and metastasis in vitro, and facilitated xenograft tumor growth and lung metastasis in vivo. Molecularly, NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB signaling, was identified to be a direct target of miR-BART13 in NPC cells, and NKIRAS2 mRNA and protein expression was inversely correlated with miR-BART13 in NPC tissues, respecitvely. Furthermore, the NF-κB signaling pathway was activated by miR-BART13. By rescued experiments, reconstitution of NKIRAS2 expression abrogated all the phenotypes upregulated by miR-BART13, and attenuated activity of NF-κB signaling pathway activated by miR-BART13 in NPC cells. Our findings indicated the newly identified miR-BART13/NKIRAS2/NF-κB signaling axis may provide further insights into better understanding of NPC initiation and development, and targeting of this pathway could be further studied as a therapeutic strategy for NPC patients.
•miR-BART13 promotes NPC cell growth and metastasis in vitro and in vivo.•NKIRAS2 is downregulated in NPC tissues and is inversely correlated with miR-BART13.•miR-BART13 activates the NF-κB signaling by directly targeting NKIRAS2 in NPC cells.
Aims
To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS).
...Methods
This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion‐weighted data were collected. We used state‐of‐the‐art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior‐parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo‐cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation.
Results
In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni‐corrected p < 0.05). NDI decreased in the bilateral thalamo‐motor and thalamo‐somatosensory tracts and in the right thalamo‐posterior‐parietal and thalamo‐occipital tracts (Bonferroni‐corrected p < 0.05). NDI reduction in the bilateral thalamo‐motor tract (p = 0.017 and 0.009) and left thalamo‐somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo‐cortical tracts, NDI yielded a higher effect size during between‐group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics.
Conclusions
Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo‐cortical connectivity in ALS.
Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo‐cortical connectivity in ALS.
The aim of this paper is to explore the stability of (weak)-minimal solutions for set-valued optimization problems via improvement sets. Firstly, the optimality and closedness of solution sets for ...the set-valued optimization problem under the upper order relation are discussed. Then, a new convergence concept for set-valued mapping sequences is introduced, and some properties of the set-valued mapping sequences are shown under the new convergence assumption. Moreover, by means of upper level sets, Painlevé-Kuratowski convergences of (weak)
E
-
u
-solutions to set-valued optimization problems with respect to the perturbations of feasible sets and objective mappings are established under mild conditions. The order that we use to establish the result depends on the improvement set, which is not necessarily a cone order. Our results can be seen as the extension of the related work established recently in this field.
Abstract
The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder ...and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach. Dynamic functional connectivity across central executive network was calculated using sliding-window approach. Functional states were estimated by K-means clustering. Right dorsolateral prefrontal cortex metabolite ratios (i.e. glutamate and glutamine complex/total creatine, myo-inositol / total creatine, and choline / total creatine) were determined. Neurocognitive performance was determined by psychometric hepatic encephalopathy scores. Minimal hepatic encephalopathy patients had decreased myo-inositol / total creatine and choline / total creatine and increased glutamate and glutamine complex / total creatine in right dorsolateral prefrontal cortex (all P ≤ 0.020); decreased static functional connectivity between bilateral dorsolateral prefrontal cortex and between right dorsolateral prefrontal cortex and lateral-inferior temporal cortex (P ≤ 0.001); increased frequency and mean dwell time in state-1 (P ≤ 0.001), which exhibited weakest functional connectivity. Central executive network dynamic functional indices were significantly correlated with right dorsolateral prefrontal cortex metabolic indices and psychometric hepatic encephalopathy scores. Right dorsolateral prefrontal cortex myo-inositol / total creatine and mean dwell time in state-1 yielded best potential for diagnosing minimal hepatic encephalopathy. Dynamic functional disturbance in central executive network may contribute to neurocognitive impairment and could be correlated with metabolic disorder.
Endoglycoceramidases (EGCases) specifically hydrolyze the glycosidic linkage between the oligosaccharide and the ceramide moieties of various glycosphingolipids, and they have received substantial ...attention in the emerging field of glycosphingolipidology. However, the mechanism regulating the strict substrate specificity of these GH5 glycosidases has not been identified. In this study, we report a novel EGCase I from Rhodococcus equi 103S (103S_EGCase I) with remarkably broad substrate specificity. Based on phylogenetic analyses, the enzyme may represent a new subfamily of GH5 glycosidases. The X-ray crystal structures of 103S_EGCase I alone and in complex with its substrates monosialodihexosylganglioside (GM3) and monosialotetrahexosylganglioside (GM1) enabled us to identify several structural features that may account for its broad specificity. Compared with EGCase II from Rhodococcus sp. M-777 (M777_EGCase II), which possesses strict substrate specificity, 103S_EGCase I possesses a longer α7-helix and a shorter loop 4, which forms a larger substrate-binding pocket that could accommodate more extended oligosaccharides. In addition, loop 2 and loop 8 of the enzyme adopt a more open conformation, which also enlarges the oligosaccharide-binding cavity. Based on this knowledge, a rationally designed experiment was performed to examine the substrate specificity of EGCase II. The truncation of loop 4 in M777_EGCase II increased its activity toward GM1 (163%). Remarkably, the S63G mutant of M777_EGCase II showed a broader substrate spectra and significantly increased activity toward bulky substrates (up to >1370-fold for fucosyl-GM1). Collectively, the results presented here reveal the exquisite substrate recognition mechanism of EGCases and provide an opportunity for further engineering of these enzymes.
Substance P (SP) is a neuropeptide released from the nervous fibers in response to injury. In addition to its association with pain and reactions to anxiety and stress, SP exerts various ...physiological functions by binding to the neurokinin-1 receptor (NK1R). However, the expression and role of SP in reparative dentinogenesis remain elusive. Here, we explored whether SP is involved in odontoblastic differentiation during reparative dentinogenesis.
Dental pulp stem cells (DPSCs) were isolated from healthy human dental pulp tissues and subjected to odontoblastic differentiation. The expression of SP and NK1R during odontoblastic differentiation was investigated in vitro. The effects of SP on odontoblastic differentiation of DPSCs were evaluated using alizarin red staining, alkaline phosphatase staining, and real-time polymerase chain reaction. After direct pulp capping with mineral trioxide aggregate, the expression of SP and NK1R during reparative dentin formation in rats were identified using histological and immunohistochemical staining.
SP and NK1R expression increased during the odontoblastic differentiation of DPSCs. SP translocated to the nucleus when DPSCs were exposed to differentiation medium. NK1R was always present in the nuclei of DPSCs and odontoblast-like cells. Additionally, we discovered that 10−8 M SP marginally enhanced the odontoblastic differentiation of DPSCs, and that these effects could be impaired by the NK1R antagonist. Furthermore, SP and NK1R were expressed in odontoblast-like and dental pulp cells during reparative dentin formation in vivo.
SP contributes to odontoblastic differentiation during reparative dentin formation by binding to the NK1R.
Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which ...could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients.
We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels.
In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients.
Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.
Diffusion magnetic resonance imaging (dMRI) studies have revealed microstructural abnormalities in white matter resulting from sleep deprivation (SD). This study aimed to adopt neurite orientation ...dispersion and density imaging (NODDI) to investigate the effect of SD on gray matter (GM) microstructural properties and its association to visuospatial memory (VSM).
Twenty-four healthy women underwent two sessions of dMRI scanning and visuospatial ability assessment by Complex Figure Test (CFT), once during rested wakefulness (RW) and once after 24 h of SD. We calculated NODDI metrics, including intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISO). Differences in NODDI-related metrics between RW and SD were determined using a voxel-wise paired
test. We identified an association between NODDI metrics and CFT results using Spearman's correlation coefficient.
Sleep deprivation worsened subjects' performance in the delayed-CFT trial. We observed no significant difference in ICVF and ODI between RW and SD. After SD, subjects showed decreases in ISO, primarily in the prefrontal cortex and temporal lobe, while exhibiting ISO increases in the anterior and posterior cerebellar lobe and cerebellar vermis. Furthermore, ISO change in the left superior, middle and inferior frontal gyrus was significantly correlated with completion time change in delayed-CFT trial performance.
Our results suggested that SD hardly affected the density and spatial organization of neurites in GM, but the extra-neurite water molecule diffusion process was affected (perhaps resulting from neuroinflammation), which contributed to VSM dysfunction.
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