Transcriptome-wide association study reveals novel susceptibility genes for coronary atherosclerosis

BackgroundGenetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association.MethodsFour TWAS approaches (PrediXcan, JTI, UTMOST, and FUSION) were used to screen genes associated with coronary atherosclerosis. Enrichment analysis of TWAS-identified genes was applied through the Metascape website. The summary-data-based Mendelian randomization (SMR) analysis was conducted to provide the evidence of causal relationship between the candidate genes and coronary atherosclerosis. At last, the cell type-specific expression of the intersection genes was examined by using human coronary artery single-cell RNA-seq, interrogating the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity.ResultsWe identified 19 genes by at least three approaches and 1 gene (NBEAL1) by four approaches. Enrichment analysis enriching the genes identified at least by two TWAS approaches, suggesting that these genes were markedly enriched in asthma and leukocyte mediated immunity reaction. Further, the summary-data-based Mendelian randomization (SMR) analysis provided the evidence of causal relationship between NBEAL1 gene and coronary atherosclerosis, confirming the protecting effects of NBEAL1 gene and coronary atherosclerosis. At last, the single cell cluster analysis demonstrated that NBEAL1 gene has differential expressions in macrophages, plasma cells and endothelial cells.ConclusionOur study identified the novel genes associated with coronary atherosclerosis and suggested the potential biological function for these genes, providing insightful guidance for further biological investigation and therapeutic approaches development in atherosclerosis-related diseases

Optimizing drip fertigation at different periods to improve yield, volatile compounds and cup quality of Arabica coffee

How to improve and regulate coffee bean yield and quality through split fertilization in the whole life cycle of coffee is still unclear and deserves further study. A field experiment of 5-year-old Arabica coffee trees was conducted for 2 consecutive years from 2020 to 2022. The fertilizer (750 kg ha-1 year-1, N-P2O5-K2O:20%-20%-20%) was split in three times at early flowering (FL), the berry expansion (BE), and the berry ripening (BR). Taking equal fertilization throughout the growth cycle (FL250BE250BR250) as the control check, variable fertilizations including FL150BE250BR350, FL150BE350BR250, FL250BE150BR350, FL250BE350BR150, FL350BE150BR250, and FL350BE250BR150. Leaf net photosynthetic rate (Anet), stomatal conductance (gs), transpiration rate (Tr), leaf water use efficiency (LWUE), carboxylation efficiency (CE), partial factor productivity of fertilizer (PFP), bean yield, crop water use efficiency (WUE), bean nutrients, volatile compounds and cup quality, and the correlation of nutrients with volatile compounds and cup quality was evaluated. FL350BE250BR150 had the maximum Anet and gs, followed by FL250BE350BR150. The highest dry bean yield and WUE were obtained from FL250BE350BR150, which increased by 8.86% and 8.47% compared with FL250BE250BR250 in two-year average. The ash, total sugar, fat, protein, caffeine and chlorogenic acid in FL250BE350BR150 were 6.47%, 9.48%, 3.60%, 14.02%, 4.85% and 15.42% higher than FL250BE250BR250. Cluster analysis indicated FL150BE350BR250, FL250BE350BR150, FL350BE150BR250 and FL350BE250BR150 under medium roasted degree increased pyrazines, esters, ketones and furans, FL150BE350BR250 and FL250BE350BR150 under dark roasted degree increased ketones and furans. The aroma, flavor, acidity and overall score of medium roasted coffee were higher than dark roasted coffee, while the body score of dark roasted coffee was higher than medium roasted coffee. The nutrient contents were correlated with the volatile compounds and cup quality. TOPSIS indicated that FL250BE350BR150 was the optimal fertilization mode in the xerothermic regions. The obtained optimum fertilization mode can provide a scientific basis for coffee fertilization optimization and management

Table_1_Effects of Dietary Phosphorus Level on the Expression of Calcium and Phosphorus Transporters in Laying Hens.pdf

<p>The transport of calcium and phosphorus is mainly relied on their corresponding transporters. The aim of this study was to determine the effect of dietary phosphorus level on the expression of the relevant calcium and phosphorus transporters in laying hens, which has a large amount of calcium and phosphorus input from intestine and output from kidney and eggshell gland. Thirty-six 25-week-old Hy-line Brown hens were fed diets with different available phosphorus level (AP, 0.15, 0.41, and 0.82%), respectively. The expression of phosphorus transporters type IIa and type IIb Na/Pi co-transporter (NPt2a, NPt2b), calcium transporter calbindin-D28k (CaBP-D28k), and plasma membrane Ca ATPase 1b (PMCA1b) were measured in small intestine, kidney, and eggshell gland by RT-PCR and western blot. The results showed that serum calcitriol and PTH concentrations were not affected (P > 0.05) by dietary AP levels. Duodenum had the highest mRNA and protein expression level of NPt2b than jejunum and ileum (P < 0.05). The protein expression abundance of CaBP-D28k and PMCA1b were higher in duodenum than that in jejunum and ileum (P < 0.05). 0.15%-AP diet upregulated the ileal mRNA expression level of NPt2b and renal mRNA expression level of NPt2a (P < 0.05), while downregulated the protein abundance of NPt2b and CaBP-D28k mRNA expression in shell gland (P < 0.05). In conclusion, both the Ca and P transporters were highly expressed in duodenum. Low AP diet decreased protein expression abundance of NPt2b in duodenum while upregulated the mRNA expression level of NPt2a in kidney. The result suggests that both the phosphorus absorption in proximal intestine and its reabsorption in kidney are involved in the adaption to low AP diet.</p

Effects of Dietary Phosphorus Level on the Expression of Calcium and Phosphorus Transporters in Laying Hens

The transport of calcium and phosphorus is mainly relied on their corresponding transporters. The aim of this study was to determine the effect of dietary phosphorus level on the expression of the relevant calcium and phosphorus transporters in laying hens, which has a large amount of calcium and phosphorus input from intestine and output from kidney and eggshell gland. Thirty-six 25-week-old Hy-line Brown hens were fed diets with different available phosphorus level (AP, 0.15, 0.41, and 0.82%), respectively. The expression of phosphorus transporters type IIa and type IIb Na/Pi co-transporter (NPt2a, NPt2b), calcium transporter calbindin-D28k (CaBP-D28k), and plasma membrane Ca ATPase 1b (PMCA1b) were measured in small intestine, kidney, and eggshell gland by RT-PCR and western blot. The results showed that serum calcitriol and PTH concentrations were not affected (P &gt; 0.05) by dietary AP levels. Duodenum had the highest mRNA and protein expression level of NPt2b than jejunum and ileum (P &lt; 0.05). The protein expression abundance of CaBP-D28k and PMCA1b were higher in duodenum than that in jejunum and ileum (P &lt; 0.05). 0.15%-AP diet upregulated the ileal mRNA expression level of NPt2b and renal mRNA expression level of NPt2a (P &lt; 0.05), while downregulated the protein abundance of NPt2b and CaBP-D28k mRNA expression in shell gland (P &lt; 0.05). In conclusion, both the Ca and P transporters were highly expressed in duodenum. Low AP diet decreased protein expression abundance of NPt2b in duodenum while upregulated the mRNA expression level of NPt2a in kidney. The result suggests that both the phosphorus absorption in proximal intestine and its reabsorption in kidney are involved in the adaption to low AP diet

Xanthanolides in Xanthium L.: Structures, Synthesis and Bioactivity

Xanthanolides were particularly characteristic of the genus Xanthium, which exhibited broad biological effects and have drawn much attention in pharmacological application. The review surveyed the structures and bioactivities of the xanthanolides in the genus Xanthium, and summarized the synthesis tactics of xanthanolides. The results indicated that over 30 naturally occurring xanthanolides have been isolated from the genus Xanthium in monomeric, dimeric and trimeric forms. The bioassay-guided fractionation studies suggested that the effective fractions on antitumor activities were mostly from weak polar solvents, and xanthatin (1) was the most effective and well-studied xanthanolide. The varieties of structures and structure-activity relationships of the xanthanolides had provided the promising skeleton for the further study. The review aimed at providing guidance for the efficient preparation and the potential prospects of the xanthanolides in the medicinal industry

Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica nanoparticles and target induced release of glucose measured with a portable glucose meter

The authors describe a novel method for the determination of glutathione (GSH). Detection is based on target induced release of glucose from MnO2 nanosheet-gated aminated mesoporous silica nanoparticles (MSNs). In detail, glucose is loaded into the pores of MSNs. Negatively charged MnO2 nanosheets are assembled on the MSNs through electrostatic interactions. The nanosheets are reduced by GSH, and this results in the release of glucose which is quantified by using a commercial electrochemical glucose meter. GSH can be quantified by this method in the 100 nM to 10 mu M concentration range, with a 34 nM limit of detection.</p

Erratum to “A Hierarchical Attention Recommender System Based on Cross-Domain Social Networks”

Search engines and recommendation systems are an essential means of solving information overload, and recommendation algorithms are the core of recommendation systems. Recently, the recommendation algorithm of graph neural network based on social network has greatly improved the quality of the recommendation system. However, these methods paid far too little attention to the heterogeneity of social networks. Indeed, ignoring the heterogeneity of connections between users and interactions between users and items may seriously affect user representation. In this paper, we propose a hierarchical attention recommendation system (HA-RS) based on mask social network, combining social network information and user behavior information, which improves not only the accuracy of recommendation but also the flexibility of the network. First, learning the node representation in the item domain through the proposed Context-NE model and then the feature information of neighbor nodes in social domain is aggregated through the hierarchical attention network. It can fuse the information in the heterogeneous network (social domain and item domain) through the above two steps. We propose the mask mechanism to solve the cold-start issues for users and items by randomly masking some nodes in the item domain and in the social domain during the training process. Comprehensive experiments on four real-world datasets show the effectiveness of the proposed method

A Hierarchical Attention Recommender System Based on Cross-Domain Social Networks

Search engines and recommendation systems are an essential means of solving information overload, and recommendation algorithms are the core of recommendation systems. Recently, the recommendation algorithm of graph neural network based on social network has greatly improved the quality of the recommendation system. However, these methods paid far too little attention to the heterogeneity of social networks. Indeed, ignoring the heterogeneity of connections between users and interactions between users and items may seriously affect user representation. In this paper, we propose a hierarchical attention recommendation system (HA-RS) based on mask social network, combining social network information and user behavior information, which improves not only the accuracy of recommendation but also the flexibility of the network. First, learning the node representation in the item domain through the proposed Context-NE model and then the feature information of neighbor nodes in social domain is aggregated through the hierarchical attention network. It can fuse the information in the heterogeneous network (social domain and item domain) through the above two steps. We propose the mask mechanism to solve the cold-start issues for users and items by randomly masking some nodes in the item domain and in the social domain during the training process. Comprehensive experiments on four real-world datasets show the effectiveness of the proposed method

Robust tracking with per‐exemplar support vector machine

The authors extend exemplar representation to the field of tracking and propose a robust tracking algorithm with per‐exemplar support vector machine (SVM) classifiers. First, the authors train the simple yet effective exemplar SVM classifier using the target object as the single positive and mining its surroundings as hard negatives. Second, the authors propose an online ensemble tracker, which integrates the useful ‘key historical templates’ of the target to refine the current template, leading to better discriminative power of tracker and effectively decreasing the risk of drift. Experiments on challenging sequences demonstrate that the tracker performs well in accuracy and robustness, especially under the sequences with strong illumination variation and scale variation, as well as pose change and partial occlusion in the long‐time sequence