Gene Transfer of Calcitonin Gene-Related Peptide Inhibits Macrophages and Inflammatory Mediators in Vein Graft Disease

Vein graft disease is a chronic inflammatory disease and limits the late results of coronary revascularization. Calcitonin gene-related peptide (CGRP) inhibits macrophages infiltrated and inflammatory mediators, we hypothesized that transfected CGRP gene inhibits macrophages infiltrated and inflammatory mediators in vein graft disease. Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of mosaic adeno-associated virus vectors containing CGRP gene (AAV2/1.CGRP) 、escherichia coli lac Z gene (AAV2/1.LacZ) or saline and then interposed in the carotid artery. Intima/media ratio were evaluated at postoperative 4 weeks, Macrophages were marked with CD68 antibody by immunocytochemistry. Inflammatory mediators were mensurated with real-time PCR. Neointimal thickening was significantly suppressed in AAV2/1.CGRP group. Macrophages infiltrated and inflammatory mediators monocyte chemoattractant protein-1 (MCP-1)、tumor necrosis factorα(TNF-α)、inducible nitricoxide synthase (iNOS)、matrix metalloproteinase-9 (MMP-9) was significantly suppressed in AAV2/1.CGRP group.Gene transfected AAV2/1.CGRP suppressed neointimal hyperplasia in vein graft disease by suppressed macrophages infiltrated and inflammatory mediators

The effects of solvent extraction on nanoporosity of marine-continental coal and mudstone

Coal and organic-rich mudstone develop massive nanopores, which control the storage of adsorbed and free gas, as well as fluid flows. Generation and retention of bitumen and hydrocarbons of oil window reservoirs add more uncertainty to the nanoporosity. Solvent extraction is a traditional way to regain unobstructed pore networks but may cause additional effects due to interactions with rocks, such as solvent adsorbing on clay surfaces or absorbing in kerogens. Selected marine-continental coal and mudstone in Eastern Ordos Basin were studied to investigate how pore structures are affected by these in-situ-sorptive compounds (namely residual bitumen and hydrocarbons) and altered by solvent extractions. Solvent extraction was performed to obtain bitumen-free subsamples. Organic petrology, bulk geochemical analyses and gas chromatography were used to characterize the samples and the extracts. Low-pressure argon and carbon dioxide adsorptions were utilized to characterize the nanopore structures of the samples before and after extraction. The samples, both coal and mudstone, are in oil windows, with vitrinite reflectance ranging from 0.807 to 1.135%. The coals are strongly affected by marine organic input, except for the sample C-4; the mudstones are sourced by either marine or terrestrial organic input, or their mixture. As for the coals affected by marine organic input, residual bitumen and hydrocarbons occupying or blocking pores <10 nm becomes weak with thermal maturation. Bitumen derived from terrestrial organic matter mainly affects small pores, since coal asphaltene molecules are much smaller than petroleum asphaltene molecules. The mudstone M-2 with high extract production showed an increase of nanopores after extraction, due to the exposure of the filled or blocked pores. However, most transitional mudstones saw decreases of the pores because pore shrinkage caused by solvents adsorbing on and swelling clay minerals (mainly kaolinite and illite/smectite mixed layers) counteracts the released pore spaces. Solvent extractions on the coals significantly increased the micropores <0.6 nm, since the heat of sorption of alkanes reaches the peak in the pores within 0.4–0.5 nm. By contrast, solvent extractions on the mudstones decreased the micropores ∼0.35 nm, which is perhaps caused by evaporative drying of solvent displacing residual water in clay

Effect of vascular endothelial growth factor rs35569394 in esophageal cancer and response to chemotherapy

The objective of this study was to investigate the possible association between the single nucleotide polymorphism (SNP), rs35569394, of the vascular endothelial growth factor gene (VEGF) and the risk of esophageal cancer (EC) in the Han Chinese population. A total of 290 EC subjects and 322 ethnically matched unrelated healthy controls free from the esophageal disease were studied. Genomic DNA was isolated from peripheral blood by salting out. Genotyping of VEGF rs35569394 polymorphism was carried out via polymerase chain reaction followed by agarose gel electrophoresis. The results showed that the distribution of genotypes was significantly different across the gender groups (p=0.032) and clinical stages (p=0.034). VEGF rs35569394 was associated with EC risk (p= 0.012, OR=1.34). A gender analysis break-down showed that rs35569394-D allele frequency was significantly higher in females than in the controls (p=0.0004, OR=1.81). Moreover, significant associations were also found in females under the dominant model (II versus ID+DD: χ2=8.18, p=0.003, OR=2.12) and the recessive model (II+ID versus DD: χ2=8.25, p=0.004, OR=2.39). Additionally, we found that the genotype, rs35569394-DD, was associated with a complete response + partial response to chemotherapy when compared with rs35569394-II (χ2=4.67, p=0.030, OR=0.47). In conclusion, our case-control study showed that the VEGF rs35569394 was significantly associated with the clinical stages and the increased risk of EC in Han Chinese females. In addition, the genotype rs35569394-DD showed a better response to chemotherapy

The prevalence of adverse reactions among individuals with three-dose COVID-19 vaccination

Background: Considering the adverse reactions to vaccination against coronavirus disease 2019 (COVID-19), some people, particularly the elderly and those with underlying medical conditions, are hesitant to be vaccinated. This study aimed to explore the prevalence of adverse reactions and provide direct evidence of vaccine safety, mainly for the elderly and people with underlying medical conditions, to receive COVID-19 vaccination. Methods: From 1st March to 30th April 2022, we conducted an online survey of people who had completed three doses of COVID-19 vaccination by convenience sampling. Adverse reaction rates and 95% confidence intervals were calculated. In addition, conditional logistic regression was used to compare the differences in adverse reactions among the elderly and those with underlying medical conditions with the general population. Results: A total of 3339 individuals were included in this study, of which 2335 (69.9%) were female, with an average age of 32.1 ± 11.4 years. The prevalence of adverse reactions after the first dose of inactivated vaccine was 24.6 % (23.1 – 26.2 %), 19.2 % (17.8 – 20.7 %) for the second dose, and 19.1 % (17.7 – 20.6 %) for the booster dose; among individuals using messenger RNA vaccines, the prevalence was 42.7 % (32.3 – 53.6 %) for the first dose, 47.2 % (36.5 – 58.1 %) for the second dose, and 46.1 % (35.4 – 57.0 %) for the booster dose. Compared with the general population, the prevalence of adverse events did not differ in individuals with underlying medical conditions and those aged 60 and above. Conclusions: For individuals with underlying medical conditions and those aged 60 and above, the prevalence of adverse reactions is similar to that of the general population, which provides a scientific basis regarding vaccination safety for these populations

Estimates of daily ground-level NO2 concentrations in China based on big data and machine learning approaches

Nitrogen dioxide (NO2) is one of the most important atmospheric pollutants. However, current ground-level NO2 concentration data are lack of either high-resolution coverage or full coverage national wide, due to the poor quality of source data and the computing power of the models. To our knowledge, this study is the first to estimate the ground-level NO2 concentration in China with national coverage as well as relatively high spatiotemporal resolution (0.25 degree; daily intervals) over the newest past 6 years (2013-2018). We advanced a Random Forest model integrated K-means (RF-K) for the estimates with multi-source parameters. Besides meteorological parameters, satellite retrievals parameters, we also, for the first time, introduce socio-economic parameters to assess the impact by human activities. The results show that: (1) the RF-K model we developed shows better prediction performance than other models, with cross-validation R2 = 0.64 (MAPE = 34.78%). (2) The annual average concentration of NO2 in China showed a weak increasing trend . While in the economic zones such as Beijing-Tianjin-Hebei region, Yangtze River Delta, and Pearl River Delta, the NO2 concentration there even decreased or remained unchanged, especially in spring. Our dataset has verified that pollutant controlling targets have been achieved in these areas. With mapping daily nationwide ground-level NO2 concentrations, this study provides timely data with high quality for air quality management for China. We provide a universal model framework to quickly generate a timely national atmospheric pollutants concentration map with a high spatial-temporal resolution, based on improved machine learning methods

Exploring the common mechanisms and biomarker ST8SIA4 of atherosclerosis and ankylosing spondylitis through bioinformatics analysis and machine learning

BackgroundAtherosclerosis (AS) is a major contributor to cerebrovascular and cardiovascular events. There is growing evidence that ankylosing spondylitis is closely linked to AS, often co-occurring with it; however, the shared pathogenic mechanisms between the two conditions are not well understood. This study employs bioinformatics approaches to identify common biomarkers and pathways between AS and ankylosing spondylitis.MethodsGene expression datasets for AS (GSE100927, GSE28829, GSE155512) and ankylosing spondylitis (GSE73754, GSE25101) were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes for AS and ankylosing spondylitis were identified using the Limma R package and weighted gene co-expression network analysis (WGCNA) techniques, respectively. The machine learning algorithm SVM-RFE was applied to pinpoint promising biomarkers, which were then validated in terms of their expression levels and diagnostic efficacy in AS and ankylosing spondylitis, using two separate GEO datasets. Furthermore, the interaction of the key biomarker with the immune microenvironment was investigated via the CIBERSORT algorithm, single-cell analysis was used to identify the locations of common diagnostic markers.ResultsThe dataset GSE100927 contains 524 DEGs associated with AS, whereas dataset GSE73754 includes 1,384 genes categorized into modules specific to ankylosing spondylitis. Analysis of these datasets revealed an overlap of 71 genes between the DEGs of AS and the modular genes of ankylosing spondylitis. Utilizing the SVM-RFE algorithm, 15 and 24 central diagnostic genes were identified in datasets GSE100927 and GSE73754, respectively. Further validation of six key genes using external datasets confirmed ST8SIA4 as a common diagnostic marker for both conditions. Notably, ST8SIA4 is upregulated in samples from both diseases. Additionally, ROC analysis confirmed the robust diagnostic utility of ST8SIA4. Moreover, analysis through CIBERSORT suggested an association of the ST8SIA4 gene with the immune microenvironment in both disease contexts. Single-cell analysis revealed that ST8SIA4 is primarily expressed in Macrophages, Monocytes, T cells, and CMPs.ConclusionThis study investigates the role of ST8SIA4 as a common diagnostic gene and the involvement of the lysosomal pathway in both AS and ankylosing spondylitis. The findings may yield potential diagnostic biomarkers and offer new insights into the shared pathogenic mechanisms underlying these conditions

cDNA Cloning and Expression Analysis of Gustavus Gene in the Oriental River Prawn Macrobrachium nipponense

The gustavus gene is required for localizing pole plasm and specifying germ cells. Research on gustavus gene expression will advance our understanding of the biological function of gustavus in animals. A cDNA encoding gustavus protein was identified and termed MnGus in the oriental river prawn Macrobrachium nipponense. Bioinformatic analyses showed that this gene encoded a protein of 262 amino acids and the protein belongs to the Spsb1 family. Real-time quantitative PCR analyses revealed that the expression level of MnGus in prawn embryos was slightly higher at the cleavage stage than at the blastula stage, and reached the maximum level during the zoea stage of embryos. The minimum level of MnGus expression occurred during the perinucleolus stage in the ovary, while the maximum was at the oil globule stage, and then the level of MnGus expression gradually decreased with the advancement of ovarian development. The expression level of MnGus in muscle was much higher than that in other tissues in mature prawn. The gustavus cDNA sequence was firstly cloned from the oriental river prawn and the pattern of gene expression was described during oocyte maturation, embryonic development, and in other tissues. The differential expression patterns of MnGus in the embryo, ovary and other somatic tissues suggest that the gustavus gene performs multiple physiological functions in the oriental river prawn