65 research outputs found
Screening of AAK1 interaction proteins and its role in regulating global translation level in cells
Objective·To investigate noval interacting partners for adaptor-associated protein kinase 1 (AAK1) and AAK1-mediated biological functions besides clathrin-mediated endocytosis.Methods·The labeled AAK1 vector and the blank control vector were transfected in HEK-293T cells, and the potential AAK1 interacting proteins were obtained by co-immunoprecipitation with agar-specific gel and mass spectrometry. Further verifications were performed by CoIP and fluorescence-based imaging. Recombinant proteins were purified in vitro and the direct interaction between proteins were confirmed by glutathione-S-transferase pulldown (GST Pulldown) assay. The regulation of AAK1 in the global protein synthesis was explored by puromycin incorporation assay.Results·Mass spectrometry results showed that AAK1 was associated with a series of proteins, including fragile X mental retardation syndrome-related protein 1 (FXR1), FXR2 and fragile X mental retardation protein 1 (FMRP). Enriching with anti-FLAG agarose gels after exogenous transfecting of AAK1-3xFLAG and FMRP-MYC plasmids, the expression of FMRP-MYC was detected. The expression of FMRP could also be detected by CoIP with endogenous AAK1 antibodies. Fluorescence-based imaging showed that they were spatially colocalized in the cytoplasm. GST Pulldown assay showed that FMRP could pulldown recombinant HIS6-AAK1 protein. Puromycin incorporation assay showed that in the same amount of time, the number of newly synthesized peptides labeled with puromycin was positively correlated with AAK1 protein expression.Conclusion·AAK1 directly interacts with FMRP in cytoplasm and could up-regulate global protein synthesis level
Deep Web Data Source Classification Based on Text Feature Extension and Extraction
With the growth of volume of high quality information in the Deep Web, as the key to utilize this information, Deep Web data source classification becomes one topic with great research value. In this paper, we propose a Deep Web data source classification method based on text feature extension and extraction. Firstly, because the data source contains less text, some data sources even contain less than 10 words. In order to classify the data source based on the text content, the original text must be extended. In text feature extension stage, we use the N-gram model to select extension words. Secondly, we proposed a feature extraction and classification method based on Attention-based Bi-LSTM. By combining LSTM and Attention mechanism, we can obtain contextual semantic representation and focus on words that are closer to the theme of the text, so that more accurate text vector representation can be obtained. In order to evaluate the performance of our classification model, some experiments are executed on the UIUC TEL-8 dataset. The experimental result shows that Deep Web data source classification method based on text feature extension and extraction has certain promotion in performance than some existing methods
MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis
MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of
multiple sclerosis
Changsheng Du1,5, Chang Liu1,5, Jiuhong Kang1,2, Guixian Zhao3, Zhiqiang Ye4, Shichao Huang1, Zhenxin Li3, Zhiying Wu3 & Gang Pei1,2
Interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate TH-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a TH-17 cell–associated microRNA,
miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer TH-17 cells and mild EAE, and its overexpression led to more TH-17 cells and severe EAE. We also found that miR-326 promoted TH-17 differentiation by targeting Ets-1, a negative regulator of TH-17 differentiation. Our data show a critical role for microRNA in TH-17 differentiation and the pathogenesis of multiple sclerosis
Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials
ObjectiveSteroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens.MethodsLiterature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method.ResultsEight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01–1.32, P = 0.04), especially in patients with severe (grade III–IV or grade C–D) aGVHD (RR = 1.26, 95% CI = 1.04–1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05–1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy.ConclusionsAdding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487
The correlation of retinal neurodegeneration and brain degeneration in patients with Alzheimer’s disease using optical coherence tomography angiography and MRI
IntroductionPathological changes in Alzheimer’s disease can cause retina and optic nerve degeneration. The retinal changes are correlated with cognitive function. This study aimed to explore the relationship of retinal differences with neuroimaging in patients with Alzheimer’s disease, analyze the association of cognitive function with retinal structure and vascular density, and identify potential additional biomarkers for early diagnosis of Alzheimer’s disease.MethodWe performed magnetic resonance imaging (MRI) scans and neuropsychological assessments in 28 patients with mild Alzheimer’s disease and 28 healthy controls. Retinal structure and vascular density were evaluated by optical coherence tomography angiography (OCTA). Furthermore, we analyzed the correlation between neuroimaging and OCTA parameters in patients with mild Alzheimer’s disease with adjustment for age, gender, years of education, and hypertension.ResultsIn patients with mild Alzheimer’s disease, OCTA-detected retinal parameters were not significantly correlated with MRI-detected neuroimaging parameters after Bonferroni correction for multiple testing. Under multivariable analysis controlled for age, gender, years of education, and hypertension, the S-Hemi (0–3) sector of macular thickness was significantly associated with Mini-cog (β = 0.583, P = 0.002) with Bonferroni-corrected threshold at P < 0.003.ConclusionOur findings suggested decreased macular thickness might be associated with cognitive function in mild AD patients. However, the differences in retinal parameters didn’t correspond to MRI-detected parameters in this study. Whether OCTA can be used as a new detection method mirroring MRI for evaluating the effect of neuronal degeneration in patients with mild Alzheimer’s disease still needs to be investigated by more rigorous and larger studies in the future
The Chinese Spring Festival Impact on Air Quality in China: A Critical Review
It is known that the sharp change of air pollutants affects air quality. Chinese Spring Festival is the most important holiday for Chinese people, and the celebration of the holiday with fireworks and the movement of people all around the country results in significant change in multiple air pollutant emissions of various sources. As many cities and rural areas suffer from the air pollution caused by firework displays and more residential fuel consumption, there is an urgency to examine the impact of the Chinese Spring Festival on air quality. Hence, this paper firstly gives an overall insight into the holiday’s impact on ambient and household air quality in China, both in urban and rural areas. The main findings of this study are: (1) The firework displays affect the air quality of urban and rural atmosphere and household air; (2) the reduction in anthropogenic emissions improves the air quality during the Chinese Spring Festival; (3) the household air in urban areas was affected most by firework burning, while the household air in rural homes was affected most by fuel consumption; and (4) the short-term health impact of air pollution during the holidays also need more concern. Although there have been many publications focused on the holiday’s impact on ambient and household air quality, most of them focused on the measurement of pollutant concentration, while studies on the formation mechanism of air pollution, the influence of meteorological conditions, and the health outcome under the effect of the Chinese Spring Festival are rare. In the future, studies focused on these processes are welcomed
Performance Evaluation of a High-Torque Permanent Magnet Brake at Operating Temperature Based on Magneto-Thermal Coupling Method
As the key component of a servo motor, the torque and temperature rise of the brake at the operating temperature affect the production quality of injection molding machines and other equipment. To achieve application of the brake and evaluate its performance at a high operating temperature, a high-torque permanent magnet brake with an axial disc structure is proposed. The permanent magnet consists of six small magnets instead of the traditional monolithic ring magnet. The key parameters of the coil are designed, and the magneto-thermal coupling method is established. The magneto-thermal coupling method considers the effect of temperature on material properties and feeds the temperature back to the electromagnetic field to correct the resistance, permeability, remanence and other coefficients. It then updates the heat source of the temperature field. The temperature rise is calculated iteratively between the electromagnetic field and the temperature field. The simulation results of the one-way method and the magneto-thermal coupling method are obtained and compared with the experimental results. The evaluation errors of the magneto-thermal coupling method for temperature and braking torque are 1.9% and 4.7% respectively, which are lower than the errors of the one-way method
Multiple Sclerosis Increases Fracture Risk: A Meta-Analysis
Purpose. The association between multiple sclerosis (MS) and fracture risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between MS and fracture risk, a meta-analysis was performed. Method. Based on comprehensive searches of the PubMed, Embase, and Web of Science, we identified outcome data from all articles estimating the association between MS and fracture risk. The pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results. A significant association between MS and fracture risk was found. This result remained statistically significant when the adjusted RRs were combined. Subgroup analysis stratified by the site of fracture suggested significant associations between MS and tibia fracture risk, femur fracture risk, hip fracture risk, pelvis fracture risk, vertebrae fracture risk, and humerus fracture risk. In the subgroup analysis by gender, female MS patients had increased fracture risk. When stratified by history of drug use, use of antidepressants, hypnotics/anxiolytics, anticonvulsants, and glucocorticoids increased the risk of fracture risk in MS patients. Conclusions. This meta-analysis demonstrated that MS was significantly associated with fracture risk
Review Article Multiple Sclerosis Increases Fracture Risk: A Meta-Analysis
. Purpose. The association between multiple sclerosis (MS) and fracture risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between MS and fracture risk, a meta-analysis was performed. Method. Based on comprehensive searches of the PubMed, Embase, and Web of Science, we identified outcome data from all articles estimating the association between MS and fracture risk. The pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results. A significant association between MS and fracture risk was found. This result remained statistically significant when the adjusted RRs were combined. Subgroup analysis stratified by the site of fracture suggested significant associations between MS and tibia fracture risk, femur fracture risk, hip fracture risk, pelvis fracture risk, vertebrae fracture risk, and humerus fracture risk. In the subgroup analysis by gender, female MS patients had increased fracture risk. When stratified by history of drug use, use of antidepressants, hypnotics/anxiolytics, anticonvulsants, and glucocorticoids increased the risk of fracture risk in MS patients. Conclusions. This meta-analysis demonstrated that MS was significantly associated with fracture risk
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