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

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

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

Cecal MicroRNAome response to Salmonella enterica serovar Enteritidis infection in White Leghorn Layer

Abstract Background Salmonella enterica serovar Enteritidis (SE) is a food-borne pathogen and of great threat to human health through consuming the contaminated poultry products. MicroRNAs (miRNAs) play an important role in different biological activities and have been shown to regulate the innate immunity in the bacterial infection. The objective of this study is to identify miRNAs associated with SE infection in laying chicken cecum. Results Average number of reads of three libraries constructed from infected and non-infected chickens was 12,476,156 and 10,866,976, respectively. There were 598 miRNAs including 194 potential novel miRNAs identified in which 37 miRNAs were significantly differentially expressed between infected and non-infected chickens. In total, 2897 unique target genes regulated by differentially expressed miRNAs were predicted, in which, 841 genes were uniquely regulated by up-regulated miRNAs (G1), 636 genes were uniquely regulated by down-regulated miRNAs (G2), and 1420 were co-regulated by both up and down- regulated miRNAs (G3). There were 118, 73 and 178 GO (Gene ontology) BP (Biological process) terms significantly enriched in G1, G2 and G3 groups, respectively. More immune-related GO BP terms than metabolism-related terms were found in G1. Expression of 12 immune-related genes of four differentially expressed miRNAs was detected through qRT-PCR. The regulatory direction of gga-miR-1416-5p, gga-miR-1662, and gga-miR-34a-5p were opposite with the target genes of TLR21 , BCL10 , TLR1LA , NOTCH2 and THBS1 , respectively. Conclusion The miRNAs contribute to the response to SE infection at the onset of egg laying through regulating the homeostasis between metabolism and immunity. The gga-miR-125b-5p, gga-miR-34a-5p, gga-miR-1416-5p and gga-miR-1662 could play an important role in SE infection through regulating their target genes. The finding herein will pave the foundation for the studies of microRNA regulation in SE infection in laying hens

The Work of Instructors for New Socialist Countryside Construction

To meet the wishes and demands of the majority of farmers, it is necessary to steadily build a new socialist countryside, and actively promote urban-rural integration. With the guidance for new countryside construction as an opportunity, this paper studies and explores the working practice of new countryside construction instructors sent by Longyang Agricultural Technique Extension Station for various village committees (or offices) during 2007-2013. This paper analyzes and summarizes the results achieved and the main problems, and puts forth the corresponding recommendations. The results of the analysis can provide a reference for the instructors to carry out the guiding work for new countryside construction