Alternative splicing enables a gene translating into different isoforms and into the corresponding proteoforms, which actually accomplish various biological functions of a living body. ...Isoform-isoform interactions (IIIs) provide a higher resolution interactome to explore the cellular processes and disease mechanisms than the canonically studied protein-protein interactions (PPIs), which are often recorded at the coarse gene level. The knowledge of IIIs is critical to map pathways, understand protein complexity and functional diversity, but the known IIIs are very scanty. In this paper, we propose a deep learning based method called DeepIII to systematically predict genome-wide IIIs by integrating diverse data sources, including RNA-seq datasets of different human tissues, exon array data, domain-domain interactions (DDIs) of proteins, nucleotide sequences and amino acid sequences. Particularly, DeepIII fuses these data to learn the representation of isoform pairs with a four-layer deep neural networks, and then performs binary classification on the learnt representation to achieve the prediction of IIIs. Experimental results show that DeepIII achieves a superior prediction performance to the state-of-the-art solutions and the III network constructed by DeepIII gives more accurate isoform function prediction. Case studies further confirm that DeepIII can differentiate the individual interaction partners of different isoforms spliced from the same gene. The code and datasets of DeepIII are available at http://mlda.swu.edu.cn/codes.php?name=DeepIII .
β-catenin and endothelial mesenchymal transformation play an important role in the formation of pulmonary hypertension. To explore the role of β-catenin in chronic thromboembolic pulmonary ...hypertension (CTEPH), we first established a rat model of CTEPH by repeated autologous thromboembolization and then treated these rats with a β-catenin specific inhibitor, XAV939, for two or four weeks. We further examined the expression of β-catenin, α-SMA and CD31, mean pulmonary artery pressure (mPAP), and histopathology in the pulmonary artery, and analyzed their correlation. In the thrombus group without treatment of the inhibitor, the expression of β-catenin and α-SMA in pulmonary artery was increased with time; mPAP, the thickness of pulmonary artery wall, and the area/total area of pulmonary artery (WA/TA) were also increased; however, the expression of CD31 was decreased. Interestingly, these symptoms could be improved by treatment with XAV939. In this study, in CTEPH rat model, the expression of β-catenin signal affects pulmonary vascular remodeling and pulmonary artery pressure, and positively correlated with pulmonary arterial endothelial mesenchymal transformation (EMT), indicating that β-catenin signal may play an important role in the occurrence and development of CTEPH. The inhibition of β-catenin signal and the improvement of pulmonary arterial EMT may provide therapeutic ideas for CTEPH.
Introduction: The role of neuraminidases in cardiovascular disease has recently gained increasing attention. However, the association between neuraminidase gene polymorphisms and heart failure (HF) ...has not yet been investigated. Methods and Results: Genotyping of nine single-nucleotide polymorphisms (SNPs) in the NEU2/NEU3/NEU4 genes was performed in 610 HF patients and 600 healthy controls from the Southwest Han Chinese population using TaqMan SNP Genotyping Assay. Individuals carrying the A allele of rs11545301 had decreased risk of HF (additive model: OR = 0.704, 95% CI = 0.511–0.97; p = 0.032). However, the C allele of rs2293763 increased the risk of HF in the recessive model (OR = 1.486, 95% CI = 1.095–2.012; p = 0.011). Rs2233384, rs2233394, and rs2293763 were significantly associated with the mortality risk of HF in the dominant model, both with and without adjustment for conventional risk factors (HR = 0.686, 95% CI = 0.52–0.906, p = 0.008 for rs2233384, HR = 1.357, 95% CI = 1.035–1.78, p = 0.027 for rs2233384, and HR = 0.76, 95% CI = 0.592–0.975, p = 0.031 for rs2293763). Conclusion: Our findings demonstrated the association between a series of variants in NEU2/NEU4 genes and the risk or prognosis of HF in the Han Chinese population. These data suggested an important role of NEU2 and NEU4 in the pathogenesis of HF.
Background
Endometrial cancer (EC) is a common malignant tumor in women with increasing mortality. The prognosis of EC is highly heterogeneous which needs more effective biomarkers for clinical ...decision. Here, we reported the effect of autophagy-related genes (ARGs) on the prognosis of EC.
Methods
The expression data of EC tissues and adjacent non-tumor samples were available from the TCGA dataset and 232 autophagy-related genes were from The Human Autophagy Database. A prognostic ARGs risk model was further constructed by using LASSO-Cox regression, and its prognostic and predictive value were evaluated by nomogram. Further functional analysis was conducted to reveal a significant signaling pathway.
Results
A total of 45 differentially expressed ARGs were obtained, including 18 upregulated and 27 downregulated genes. Eleven ARGs (BID, CAPN2, CDKN2A, DLC1, GRID2, IFNG, MYC, NRG3, P4HB, PTK6, and TP73) were finally selected to build ARGs risk. This signature could well distinguish between the high- and low-risk patients (survival analysis:
P
= 1.18E-10; AUC: 0.733 at 1 year, 0.795 at 3 years, and 0.823 at 5 years). Furthermore, a nomogram was plotting to predict the possibility of overall survival and suggested good value for clinical utility.
Conclusion
We established an eleven-ARG signature, which was probably effective in the prognostic prediction of patients with EC.
White rot fungi is capable of oxidizing many persistent organic pollutants including dyes. The application of the fungi has been limited for wastewater treatment under non-sterile conditions due to ...the contamination by bacteria and other micro-organisms. We developed a treatment approach by using immobilized white rot fungi
Phanerochaete chrysosporium to degrade reactive dye K-2BP under non-sterile condition. Four different inert carriers were tested for immobilization of the white rot fungi with orthogonal experiments in comparison with suspension culture. The activity of manganese peroxidase (MnP) was used for the evaluation of oxidization performance in order to understand whether contamination of bacteria and other micro-organisms was suppressed. Under non-sterile conditions, the immobilized fungal cultures successfully restrained the growth of microzymes, coccies, and bacillus but suspension culture was highly contaminated with poor MnP activity. Under non-sterile conditions, higher MnP enzymatic activity (690
U/L vs. 125
U/L), higher decolorization efficiency (93.5% vs. 15%) and shorter reaction period (3 days vs. 6 days) were achieved in immobilized cultures in comparison with suspension culture. With the immobilized fungal cultures, no difference was observed under non-sterile and sterile conditions for the degradation of reactive dye K-2BP.
We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which ...are bench‐stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction. We further demonstrate the utility of this method in the late‐stage modification of complex drug molecules, including the anticancer agent camptothecin. Experimental studies provide insight into the reaction mechanism.
Glycosyl radicals were generated under acidic conditions for the first time by the use of glycosyl sulfinates as precursors. This development enables the installation of glycosyl units directly onto pharmaceutically relevant pyridine cores by the Minisci reaction.
Introduction The role of neuraminidases in cardiovascular disease has recently gained increasing attention. However, the association between neuraminidase gene polymorphisms and heart failure (HF) ...has not yet been investigated. Methods and Results Genotyping of nine single nucleotide polymorphisms (SNPs) in the NEU2/NEU3/NEU4 genes was performed in 610 HF patients and 600 healthy controls from the Southwest Han Chinese population using TaqMan SNP Genotyping Assay. Individuals carrying the A allele of rs11545301 had decreased risk of HF (additive model: OR=0.704, 95% CI=0.511-0.97; P = 0.032). While the C allele of rs2293763 increased the risk of HF in recessive model (OR=1.486, 95% CI=1.095-2.012; P = 0.011). Rs2233384, rs2233394 and rs2293763 were significantly associated with the mortality risk of HF in dominant model, both with and without adjustment for conventional risk factors (HR= 0.686, 95% CI= 0.52-0.906, P = 0.008 for rs2233384; HR= 1.357, 95% CI= 1.035-1.78, P = 0.027 for rs2233384 and HR= 0.76, 95% CI= 0.592-0.975; P = 0.031 for rs2293763). Conclusion Our findings demonstrated the association between a series of variants in NEU2/NEU4 genes and the risk or prognosis of HF in Han Chinese Population. These data suggested an important role of NEU2 and NEU4 in the pathogenesis of HF.
Clinical characteristics of patients with pulmonary thromboembolism have been described in previous studies. Although very old patients with pulmonary thromboembolism are a special group based on ...comorbidities and age, they do not receive special attention.
This study aims to explore the clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism in a relatively large population.
The study included a total of 7438 patients from a national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES). Consecutive patients with acute pulmonary thromboembolism were enrolled and were divided into three groups. Comparisons were performed between these three groups in terms of clinical characteristics, comorbidities and in-hospital prognosis. Mortality predictors were analyzed in very old patients with pulmonary embolism.
In 7,438 patients with acute pulmonary thromboembolism, 609 patients aged equal to or greater than 80 years (male 354 (58.1%)). There were 2743 patients aged between 65 and 79 years (male 1313 (48%)) and 4095 patients aged younger than 65 years (male 2272 (55.5%)). Patients with advanced age had significantly more comorbidities and worse condition, however, some predisposing factors were more obvious in younger patients with pulmonary thromboembolism. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2, malignancy, anticoagulation as first therapy were mortality predictors for all-cause death in very old patients with pulmonary thromboembolism. The analysis found that younger patients were more likely to have chest pain, hemoptysis (the difference was statistically significant) and dyspnea triad.
In very old population diagnosed with pulmonary thromboembolism, worse laboratory results, atypical symptoms and physical signs were common. Mortality was very high and comorbid conditions were their features compared to younger patients. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2 and malignancy were positive mortality predictors for all-cause death in very old patients with pulmonary thromboembolism while anticoagulation as first therapy was negative mortality predictors.
