Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Background Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Immune checkpoint molecules expressed on CD4+ T cells play critical roles in chronic HBV infection. However, their roles in chronic asymptomatic HBV carriers (ASCs) with hepatitis B e antigen (HBeAg)-negative remain unclear. In this study, we explored the role of immune checkpoint molecules expressed on CD4+ T cell subsets in chronic ASCs with HBeAg-negative. Methods Human peripheral blood mononuclear cells (PBMCs) from the ASCs with HBeAg-negative and healthy controls (HC) were isolated, and immune checkpoint molecules expressed on CD4+ T cell subsets and serum cytokines were detected by flow cytometry. Moreover, the mRNA expressions of immune checkpoint molecules were analyzed by a real-time quantitative PCR assay. Results In comparison with HC, CD4+ T cells highly expressed LAG-3, TIM-3, and PD-1 in PBMCs from chronic ASCs with HBeAg-negative. Interestingly, the expressions of TIM-3 and PD-1 on circulating follicular helper T (Tfh) cells in ASCs were significantly high. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were different among Treg, Th1, Th2, and Th17 cells. In addition, the expressions of TIM-3 and CTLA-4 mRNA in PBMCs from ASCs were significantly elevated. However, the frequency of CTLA-4+CD4+ T cell subsets in PBMCs from ASCs was not different from HC. The levels of six cytokines in serum from ASCs were not clearly different from HC. Conclusion Immune checkpoint molecules highly expressed on CD4+ T cell subsets indicated an important role in chronic ASCs with HBeAg-negative, which provided potential therapeutic targets in the pathogenesis of chronic HBV infection.
Bifidobacterium Treated by Electrostatic Spray Drying Relieved Constipation by Changing the Relative Abundance of Bacteria Associated With Gastrointestinal Regulatory Peptides

In this study, three different microencapsulation methods were used to embed Bifidobacterium to explore the alleviating effects of embedding methods on constipated mice. By measuring the defecation-related parameters, it was found that the Bifidobacteria treated by electrostatic spray drying had the best ability to relieved constipation. Furthermore, by detecting constipation-related gastrointestinal regulatory peptides, inflammatory factors, intestinal microbiota, and SCFAs, it was discovered that Bifidobacteria treated by electrostatic spray drying changed the composition of intestinal microbiota, especially the relative abundance of bacteria that were positively correlated with AQP3, but negatively correlated with ET-1 and SS, then increased the level of AQP3 in the intestine, and finally relieved constipation by increasing the fecal water content and small intestinal propulsion rate. In conclusion, the electrostatic spray drying method was superior to the other two methods in maintaining the activity of Bifidobacteria and relieved constipation by changing the relative abundance of bacteria that were correlated with gastrointestinal regulatory peptides and increasing the content of fecal water and small intestinal propulsion rate.
Numerical Method for Predicting and Evaluating the Stability of Section Coal Pillars in Underground Longwall Mining

The stability of section coal pillars is one of the most important factors affecting the stability of coal rock systems in the stope and roadway. This study aimed to develop an artificial intelligence methodology to predict and evaluate coal pillar stability. Data from 125 published coal pillar historical cases were collected to build a sample dataset. Meanwhile, a mean impact value-genetic algorithm-back propagation neural network (MIV-GA-BP) fusion model was established to predict the stability of section coal pillars. MIV tests indicated that the main factors influencing coal pillar stability are (in order of decreasing importance): the coal seam buried depth > coal seam thickness > working face length > coal elastic modulus > cohesion > tensile strength > internal friction angle > Poisson’s ratio > volume weight > coal seam dip angle. The relative weights of mine design parameters are generally greater than those of the physical and mechanical parameters of coal and rock mass. After the BP model was optimized by GA, the relative error, R value, and mean squared error were 5%, 0.95, and 0.13, respectively. These results confirm that the machine learning model has significant potential for improving coal pillar stability evaluations. The developed prediction model was applied to two field cases to verify its effectiveness, and the results indicated that the innovative method can be extended for use in similar geological conditions or other mining and geaological engineering fields.
Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

The immune system is generally known to be the primary defense mechanism against pathogens. Any pathological conditions are reflected in anomalies in the immune system parameters. Increasing evidence suggests the involvement of immune dysregulation and neuroinflammation in the pathogenesis of schizophrenia. In this systematic review, we summarized the available evidence of abnormalities in the immune system in schizophrenia. We analyzed impairments in all immune system components and assessed the level of bias in the available evidence. It has been shown that schizophrenia is associated with abnormalities in all immune system components: from innate to adaptive immunity and from humoral to cellular immunity. Abnormalities in the immune organs have also been observed in schizophrenia. Evidence of increased C-reactive protein, dysregulation of cytokines and chemokines, elevated levels of neutrophils and autoantibodies, and microbiota dysregulation in schizophrenia have the lowest risk of bias. Peripheral immune abnormalities contribute to neuroinflammation, which is associated with cognitive and neuroanatomical alterations and contributes to the pathogenesis of schizophrenia. However, signs of severe inflammation are observed in only about 1/3 of patients with schizophrenia. Immunological parameters may help identify subgroups of individuals with signs of inflammation who well respond to anti-inflammatory therapy. Our integrative approach also identified gaps in knowledge about immune abnormalities in schizophrenia, and new horizons for the research are proposed.
Spatial Pattern and Dynamic Change of Vegetation Greenness From 2001 to 2020 in Tibet, China

Due to the cold climate and dramatically undulating altitude, the identification of dynamic vegetation trends and main drivers is essential to maintain the ecological balance in Tibet. The normalized difference vegetation index (NDVI), as the most commonly used greenness index, can effectively evaluate vegetation health and spatial patterns. MODIS-NDVI (Moderate-resolution Imaging Spectroradiometer-NDVI) data for Tibet from 2001 to 2020 were obtained and preprocessed on the Google Earth Engine (GEE) cloud platform. The Theil–Sen median method and Mann–Kendall test method were employed to investigate dynamic NDVI changes, and the Hurst exponent was used to predict future vegetation trends. In addition, the main drivers of NDVI changes were analyzed. The results indicated that (1) the vegetation NDVI in Tibet significantly increased from 2001 to 2020, and the annual average NDVI value fluctuated between 0.31 and 0.34 at an increase rate of 0.0007 year−1; (2) the vegetation improvement area accounted for the largest share of the study area at 56.6%, followed by stable unchanged and degraded areas, with proportions of 27.5 and 15.9%, respectively. The overall variation coefficient of the NDVI in Tibet was low, with a mean value of 0.13; (3) The mean value of the Hurst exponent was 0.53, and the area of continuously improving regions accounted for 41.2% of the study area, indicating that the vegetation change trend was continuous in most areas; (4) The NDVI in Tibet indicated a high degree of spatial agglomeration. However, there existed obvious differences in the spatial distribution of NDVI aggregation areas, and the aggregation types mainly included the high-high and low-low types; and (5) Precipitation and population growth significantly contributed to vegetation cover improvement in western Tibet. In addition, the use of the GEE to obtain remote sensing data combined with time-series data analysis provides the potential to quickly obtain large-scale vegetation change trends.
The Value of H2BC12 for Predicting Poor Survival Outcomes in Patients With WHO Grade II and III Gliomas

Purpose: Glioma is a common primary malignant brain tumor. Grade II (GII) gliomas are prone to develop into anaplastic grade III (GIII) gliomas, which indicate a higher malignancy and poorer survival outcome. This study aimed to satisfy the increasing demand for novel sensitive biomarkers and potential therapeutic targets in the treatment of GII and GIII gliomas. Methods: A TCGA dataset was used to investigate the expression of H2BC12 mRNA in GII and GIII gliomas and its relation to clinical pathologic characteristics. Glioma tissues were collected to verify results from the TCGA dataset, and H2BC12 mRNA was detected by RT-qPCR. ROC analysis was employed to evaluate the classification power for GII and GIII. The significance of H2BC12 mRNA GII and GIII gliomas was also investigated. In addition, H2BC12 expression-related pathways were enriched by gene set enrichment analysis (GSEA). DNA methylation level and mutation of H2BC12 were analyzed by the UALCAN and CBioPortal databases, respectively. Results: Based on the sample data from multiple databases and RT-qPCR, higher expression of H2BC12 mRNA was found in GII and GIII glioma tissue compared to normal tissue, which was consistent with a trend with our clinical specimen. H2BC12 mRNA had a better power in distinguishing between GII and GIII and yielded an AUC of 0.706 with a sensitivity of 76.9% and specificity of 81.8%. Meanwhile, high H2BC12 levels were associated with IDH status, 1p/19q codeletion, primary therapy outcome, and the histological type of gliomas. Moreover, the overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) of GII glioma patients with higher levels of H2BC12 were shorter than those of patients with lower levels as well as GIII patients. In the multivariate analysis, a high H2BC12 level was an independent predictor for poor survival outcomes of gliomas. The Wnt or PI3K-AKT signaling pathways, DNA repair, cellular senescence, and DNA double-strand break repair were differentially activated in phenotypes that were positively associated with H2BC12. H2BC12 DNA methylation was high in TP53 nonmutant patients, and no H2BC12 mutation was observed in gliomas patients. Conclusion: H2BC12 is a promising biomarker for the diagnosis and prognosis of patients with WHO grade II and III gliomas.
Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) is the most common type of sleep apnea that impacts the development or progression of many other disorders. Abnormal expression of N6-methyladenosine (m6A) RNA modification regulators have been found relating to a variety of human diseases. However, it is not yet known if m6A regulators are involved in the occurrence and development of OSA. Herein, we aim to explore the impact of m6A modification in severe OSA. Methods: We detected the differentially expressed m6A regulators in severe OSA microarray dataset GSE135917. The least absolute shrinkage and selection operator (LASSO) and support vector machines (SVM) were used to identify the severe OSA-related m6A regulators. Receiver operating characteristic (ROC) curves were performed to screen and verify the diagnostic markers. Consensus clustering algorithm was used to identify m6A patterns. And then, we explored the character of immune microenvironment, molecular functionals, protein-protein interaction networks and miRNA-TF coregulatory networks for each subcluster. Finally, the Connectivity Map (CMap) tools were used to tailor customized treatment strategies for different severe OSA subclusters. An independent dataset GSE38792 was used for validation. Results: We found that HNRNPA2B1, KIAA1429, ALKBH5, YTHDF2, FMR1, IGF2BP1 and IGF2BP3 were dysregulated in severe OSA patients. Among them, IGF2BP3 has a high diagnostic value in both independent datasets. Furthermore, severe OSA patients can be accurately classified into three m6A patterns (subcluster1, subcluster2, subcluster3). The immune response in subcluster3 was more active because it has high M0 Macrophages and M2 Macrophages infiltration and up-regulated human leukocyte antigens (HLAs) expression. Functional analysis showed that representative genes for each subcluster in severe OSA were assigned to histone methyltransferase, ATP synthesis coupled electron transport, virus replication, RNA catabolic, multiple neurodegeneration diseases pathway, et al. Moreover, our finding demonstrated cyclooxygenase inhibitors, several of adrenergic receptor antagonists and histamine receptor antagonists might have a therapeutic effect on severe OSA. Conclusion: Our study presents an overview of the expression pattern and crucial role of m6A regulators in severe OSA, which may provide critical insights for future research and help guide appropriate prevention and treatment options.
A Newly Isolated Strain of Haematococcus pluvialis GXU-A23 Improves the Growth Performance, Antioxidant and Anti-Inflammatory Status, Metabolic Capacity and Mid-intestine Morphology of Juvenile Litopenaeus vannamei

Haematococcus pluvialis can be used as a green additive in aquafeeds due to it contains rich astaxanthin and polyunsaturated fatty acid. In the present study, a newly strain of H. pluvialis GXU-A23 with high concentration of astaxanthin was firstly isolated by a newly culture strategy in our laboratory. In addition, H. pluvialis GXU-A23 was applied in the Litopenaeus vannamei feed for determining whether it has positive effects on the growth performance, antioxidant and anti-inflammatory status, metabolic capacity and mid-intestine morphology of juvenile L. vannamei. Shrimp with 0.63 g approximately initial body weight were fed diets supplemented with/without 50 g/kg H. pluvialis GXU-A23. After 8 weeks feeding intervention, significantly higher growth performance of L. vannamei was obtained in the H. pluvialis GXU-A23 treatment group compared to the control group (p < 0.05). At the same time, L. vannamei fed with H. pluvialis GXU-A23 acquired significantly better antioxidant and anti-inflammatory status than the control group (p < 0.05). In addition, higher RNA expression level of hepatopancreas digestive enzyme, hepatopancreas lipid and glucose metabolic enzymes as well as better mid-intestine morphology were found in the H. pluvialis GXU-A23 treatment group than the control group (p < 0.05). These results indicated that 50 g/kg H. pluvialis GXU-A23 was suitable for the L. vannamei feed, which could improve the growth performance, antioxidant and anti-inflammatory status, metabolic capacity and mid-intestine morphology of juvenile L. vannamei.
Acute Cerebral Ischemia Increases a Set of Brain-Specific miRNAs in Serum Small Extracellular Vesicles

Small extracellular vesicles (sEVs) miRNAs are promising diagnosis and prognosis biomarkers for ischemic stroke (IS). This study aimed to determine the impact of IS on the serum sEVs miRNA profile of IS patients and a transient middle cerebral artery occlusion (tMCAO) mouse model. Small RNAseq was used to define the serum sEVs miRNA profile in IS patients and healthy controls (HC), and tMCAO mice and sham controls. Among the 1,444 and 1,373 miRNAs identified in human and mouse serum sEVs, the expression of 424 and 37 miRNAs was significantly altered in the IS patients and tMCAO mice, respectively (| Log2FC| ≥ 1, p < 0.01). Notably, five of the top 25 upregulated miRNAs in IS patients were brain-specific or enriched, including hsa-miR-9-3p, hsa-miR-124-3p, hsa-miR-143-3p, hsa-miR-98-5p, and hsa-miR-93-5p. Upregulation of these four miRNAs was further validated by qPCR. Nine of the 20 upregulated miRNAs in tMCAO mice were also brain-specific or enriched miRNAs. Temporal analysis indicated that the dynamics of mmu-miR-9-5p, mmu-miR-124-3p, mmu-miR-129-5p, and mmu-miR-433-3p were closely correlated with the evolution of ischemic brain injury, as their expression increased at 0.5 days after the onset of ischemia, peaked at day 1 or 3, and returned to normal levels at day 7 and 14. Notably, with the exceptions of mmu-miR-128-3p, the expression of the other eight miRNAs in the mouse serum sEVs was unaffected in the lipopolysaccharide (LPS)-induced neuroinflammation model. Together, in this study, we provided a comprehensive view of the influences of IS on the serum sEVs miRNA profile of IS patients and tMCAO mice and demonstrated the increment of a set of brain-specific miRNAs in serum sEVs after acute cerebral ischemia, which could be promising candidates directly reflecting the ischemic brain injury.
Effect of a Web-Based Project on Preservice and Inservice Teachers’ Attitude toward Computers and Their Technology Skills

Abstract This study examined the effectiveness of a Web-based project in improving preservice and inservice teachers’ attitude toward computers and their technology skills. Thirty-one preservice and inservice students who were enrolled in a Special Education course participated in the study and completed pre and post surveys assessing their attitude toward computers and their proficiency in using technology. Results indicated that there was a significant improvement in students’ attitude toward computers and their technology skills after completing the Web-based project. Student feedback provided after completing the project provides further insights about why attitudes changed. The findings of this study suggest that a single project can be effective in improving attitudes toward technology and building skills, if it is meaningful and useful.
Codonopsis pilosula Polysaccharide Improved Spleen Deficiency in Mice by Modulating Gut Microbiota and Energy Related Metabolisms

Codonopsis Radix (CR) is an important traditional Chinese medicine used for the treatment of spleen deficiency syndrome (SDS). Codonopsis pilosula polysaccharides (CPP) in CR are considered to be responsible for tonifying the spleen function; however, the mechanisms of the polysaccharides have remained unclear. This study aimed to investigate the treatment mechanisms of CPP in SDS mice using a combinational strategy of 16S rRNA gene sequencing and targeted metabolomics. Here, studies demonstrated that CPP had invigorating effect in vivo in Sennae Folium-induced SDS in mice by organ indexes, D-xylose determination, gastrointestinal hormones levels and goblet cells observation. Antibiotic treatment revealed that the intestinal microbiota was required for the invigorating spleen effect of CPP. Furthermore, gut microbiota analysis found that CPP significantly enriched probiotic Lactobacillus and decreased the abundance of some opportunistic pathogens, such as Enterococcus and Shigella. The metabolic profile analysis of the colonic content revealed that 25 chemicals were altered significantly by CPP, including amino acids, organic acids, fatty acids, carbohydrates and carnitine etc., which are mainly related to “energy conversion” related processes such as amino acids metabolism, tricarboxylic acid cycle, and nitrogen metabolism. Spearman’s correlation assays displayed there were strong correlations among biochemical indicators-gut microbiota-metabolomics. In summary, these results provided a new perspective for CPP improving SDS by regulating energy metabolism related bacteria and pathways.
On the Utilization of Dietary Glycerol in Carnivorous Fish - Part I: Insights Into Hepatic Carbohydrate Metabolism of Juvenile Rainbow Trout (Oncorhynchus mykiss) and European Seabass (Dicentrarchus labrax)

Glycerol is a 3-carbon sugar alcohol successfully employed as an alternative feed ingredient for land-farmed animals and more recently for farmed fish. While most studies address zootechnical performance, few have delved into the metabolic utilization of dietary glycerol. A growth trial was performed using diets with increasing levels of glycerol (0, 2.5 and 5%) on two relevant species for aquaculture: rainbow trout (8-week trial; 3 tank per diet/25 fish per tank, on a 15 ± 1°C flow-through freshwater system); and European seabass (6-week trial; 5 tank per diet/6-8 fish per tank on a 21°C indoor saltwater RAS system). After this period, fish were subjected to a metabolic trial consisting of a 6-day residence in deuterated water (2H2O). Measurements of blood glucose and hepatic glycogen 2H-enrichments through Nuclear Magnetic Resonance, complemented by mRNA levels of key-enzymes for intermediary metabolism were used to evaluate the catabolic pathways of dietary glycerol. Dietary glycerol had no impact on plasma glucose, but hepatic glycogen levels increased significantly with increasing dietary glycerol levels in both species. While trout was able to regulate circulating glycerol plasma, seabass presented elevated levels on the glycerol-supplemented diets. Despite revealing some significant differences between sampling time (6 and 24 h), none of the enzymes’ mRNA levels responded to the dietary treatment. In trout, the main source of blood glucose was not labeled with 2H (~60%, likely from diet) while other contributors did not differ with glycerol supplementation. In seabass, the unlabeled contribution was approximately half of that observed in trout (~30%), accompanied by a significant increase of gluconeogenic contributions at the triose-phosphate level to the blood glucose with increasing dietary glycerol. In trout, labeling from 2H2O into hepatic glycogen revealed significant differences, with the contribution from the indirect pathway at the triose-phosphate level increasing with increased dietary glycerol. No such differences were found in seabass’ glycogen pool. These findings suggest that fish species are able to retain, catabolize glycerol and incorporate it into carbohydrates. The gluconeogenic utilization of exogenous glycerol differed between species and affected the synthesis of hepatic glycogen in trout and the appearance of blood glucose in seabass.