Identification of disease-related genes and construction of a gene co-expression database in non-alcoholic fatty liver disease

Background: The mechanism of NAFLD progression remains incompletely understood. Current gene-centric analysis methods lack reproducibility in transcriptomic studies.Methods: A compendium of NAFLD tissue transcriptome datasets was analyzed. Gene co-expression modules were identified in the RNA-seq dataset GSE135251. Module genes were analyzed in the R gProfiler package for functional annotation. Module stability was assessed by sampling. Module reproducibility was analyzed by the ModulePreservation function in the WGCNA package. Analysis of variance (ANOVA) and Student’s t-test was used to identify differential modules. The receiver operating characteristic (ROC) curve was used to illustrate the classification performance of modules. Connectivity Map was used to mine potential drugs for NAFLD treatment.Results: Sixteen gene co-expression modules were identified in NAFLD. These modules were associated with multiple functions such as nucleus, translation, transcription factors, vesicle, immune response, mitochondrion, collagen, and sterol biosynthesis. These modules were stable and reproducible in the other 10 datasets. Two modules were positively associated with steatosis and fibrosis and were differentially expressed between non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL). Three modules can efficiently separate control and NAFL. Four modules can separate NAFL and NASH. Two endoplasmic reticulum related modules were both upregulated in NAFL and NASH compared to normal control. Proportions of fibroblasts and M1 macrophages are positively correlated with fibrosis. Two hub genes Aebp1 and Fdft1 may play important roles in fibrosis and steatosis. m6A genes were strongly correlated with the expression of modules. Eight candidate drugs for NAFLD treatment were proposed. Finally, an easy-to-use NAFLD gene co-expression database was developed (available at https://nafld.shinyapps.io/shiny/).Conclusion: Two gene modules show good performance in stratifying NAFLD patients. The modules and hub genes may provide targets for disease treatment

Brain Network and Abnormal Hemispheric Asymmetry Analyses to Explore the Marginal Differences in Glucose Metabolic Distributions Among Alzheimer's Disease, Parkinson's Disease Dementia, and Lewy Body Dementia

Facilitating accurate diagnosis and ensuring appropriate treatment of dementia subtypes, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Lewy body dementia (DLB), is clinically important. However, the differences in glucose metabolic distribution among these three dementia subtypes are minor, which can result in difficulties in diagnosis by visual assessment or traditional quantification methods. Here, we explored this issue using novel approaches, including brain network and abnormal hemispheric asymmetry analyses. We generated 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images from patients with AD, PDD, and DLB, and healthy control (HC) subjects (n = 22, 18, 22, and 22, respectively) from Huashan hospital, Shanghai, China. Brain network properties were measured and between-group differences evaluated using graph theory. We also calculated and explored asymmetry indices for the cerebral hemispheres in the four groups, to explore whether differences between the two hemispheres were characteristic of each group. Our study revealed significant differences in the network properties of the HC and AD groups (small-world coefficient, 1.36 vs. 1.28; clustering coefficient, 1.48 vs. 1.59; characteristic path length, 1.57 vs. 1.64). In addition, differing hub regions were identified in the different dementias. We also identified rightward asymmetry in the hemispheric brain networks of patients with AD and DLB, and leftward asymmetry in the hemispheric brain networks of patients with PDD, which were attributable to aberrant topological properties in the corresponding hemispheres

Subsidized housing, life chances and poverty alleviation : evidence from Guangzhou, China

abstractUrban Planning and DesignDoctoralDoctor of Philosoph

A new approach to fault-line selection of small current neutral grounding system

In this paper, a new approach combining BP neural network with fuzzy Petri net (FPN) is developed to deal with the issue of fault-line selection of the small current neutral grounding system. First, the preliminaries of the FPN are briefly introduced. Then, the model of the fault-line selection is detailedly described to explain the new feature representation that fuses multiple fault features of the lines, including the wavelet energy, the active component and the fifth harmonic component. Finally, the simulation model of the fault-line selection is constructed, and the simulation experiments are carried out to verify the effectiveness of the new approach, which could be superior to the traditional fault-line selection approaches

A risk stratification and prognostic prediction model for lung adenocarcinoma based on aging-related lncRNA

Abstract To create a risk model of aging-related long non-coding RNAs (arlncRNAs) and determine whether they might be useful as markers for risk stratification, prognosis prediction, and targeted therapy guidance for patients with lung adenocarcinoma (LUAD). Data on aging genes and lncRNAs from LUAD patients were obtained from Human Aging Genomic Resources 3 and The Cancer Genome Atlas, and differential co-expression analysis of established differentially expressed arlncRNAs (DEarlncRNAs) was performed. They were then paired with a matrix of 0 or 1 by cyclic single pairing. The risk coefficient for each sample of LUAD individuals was obtained, and a risk model was constructed by performing univariate regression, least absolute shrinkage and selection operator regression analysis, and univariate and multivariate Cox regression analysis. Areas under the curve were calculated for the 1-, 3-, and 5-year receiver operating characteristic curves to determine Akaike information criterion-based cutoffs to identify high- and low-risk groups. The survival rate, correlation of clinical characteristics, malignant-infiltrating immune-cell expression, ICI-related gene expression, and chemotherapeutic drug sensitivity were contrasted with the high- and low-risk groups. We found that 99 DEarlncRNAs were upregulated and 12 were downregulated. Twenty pairs of DEarlncRNA pairs were used to create a prognostic model. The 1-, 3-, and 5-year survival curve areas of LUAD individuals were 0.805, 0.793, and 0.855, respectively. The cutoff value to classify patients into two groups was 0.992. The mortality rate was higher in the high-risk group. We affirmed that the LUAD outcome-related independent predictor was the risk score (p < 0.001). Validation of tumor-infiltrating immune cells and ICI-related gene expression differed substantially between the groups. The high-risk group was highly sensitive to docetaxel, erlotinib, gefitinib, and paclitaxel. Risk models constructed from arlncRNAs can be used for risk stratification in patients with LUAD and serve as prognostic markers to identify patients who might benefit from targeted and chemotherapeutic agents

Brain Network and Abnormal Hemispheric Asymmetry Analyses to Explore the Marginal Differences in Glucose Metabolic Distributions Among Alzheimer's Disease, Parkinson's Disease Dementia, and Lewy Body Dementia

Facilitating accurate diagnosis and ensuring appropriate treatment of dementia subtypes, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Lewy body dementia (DLB), is clinically important. However, the differences in glucose metabolic distribution among these three dementia subtypes are minor, which can result in difficulties in diagnosis by visual assessment or traditional quantification methods. Here, we explored this issue using novel approaches, including brain network and abnormal hemispheric asymmetry analyses. We generated 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images from patients with AD, PDD, and DLB, and healthy control (HC) subjects (n = 22, 18, 22, and 22, respectively) from Huashan hospital, Shanghai, China. Brain network properties were measured and between-group differences evaluated using graph theory. We also calculated and explored asymmetry indices for the cerebral hemispheres in the four groups, to explore whether differences between the two hemispheres were characteristic of each group. Our study revealed significant differences in the network properties of the HC and AD groups (small-world coefficient, 1.36 vs. 1.28; clustering coefficient, 1.48 vs. 1.59; characteristic path length, 1.57 vs. 1.64). In addition, differing hub regions were identified in the different dementias. We also identified rightward asymmetry in the hemispheric brain networks of patients with AD and DLB, and leftward asymmetry in the hemispheric brain networks of patients with PDD, which were attributable to aberrant topological properties in the corresponding hemispheres