ResNorm: Tackling Long-tailed Degree Distribution Issue in Graph Neural Networks via Normalization

Graph Neural Networks (GNNs) have attracted much attention due to their ability in learning representations from graph-structured data. Despite the successful applications of GNNs in many domains, the optimization of GNNs is less well studied, and the performance on node classification heavily suffers from the long-tailed node degree distribution. This paper focuses on improving the performance of GNNs via normalization. In detail, by studying the long-tailed distribution of node degrees in the graph, we propose a novel normalization method for GNNs, which is termed ResNorm (\textbf{Res}haping the long-tailed distribution into a normal-like distribution via \textbf{norm}alization). The $scale$ operation of ResNorm reshapes the node-wise standard deviation (NStd) distribution so as to improve the accuracy of tail nodes (\textit{i}.\textit{e}., low-degree nodes). We provide a theoretical interpretation and empirical evidence for understanding the mechanism of the above $scale$. In addition to the long-tailed distribution issue, over-smoothing is also a fundamental issue plaguing the community. To this end, we analyze the behavior of the standard shift and prove that the standard shift serves as a preconditioner on the weight matrix, increasing the risk of over-smoothing. With the over-smoothing issue in mind, we design a $shift$ operation for ResNorm that simulates the degree-specific parameter strategy in a low-cost manner. Extensive experiments have validated the effectiveness of ResNorm on several node classification benchmark datasets

Molecular marker analysis of ‘Shatangju’ and ‘Wuzishatangju’ mandarin (Citrus reticulata Blanco)

‘Wuzishatangju’(Citrus reticulata Blanco) is an excellent cultivar derived from a bud sport of a seedy ‘Shatangju’ cultivar found in Guangdong Province in the 1980s. In this study, six molecular markers including random amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), simple sequence repeat (SSR), sequence-related amplified polymorphism (SRAP), inter-retrotransposn amplified polymorphism (IRAP) and retrotransposon-microsatellite amplified polymorphism (REMAP) were used to study the genetic variations between ‘Shatangju’ and ‘Wuzishatangju’. 1196 RAPD, seven SSR, 28 IRAP and 56 REMAP primers were used to detect the genetic variations between ‘Shatangju’ and ‘Wuzishatangju’. However, no difference was observed between the two cultivars. These results indicate that there was a very close genetic relationship between ‘Shatangju’ and ‘Wuzishatangju’ and RAPD, SSR, IRAP and REMAP markers could not distinguish them. Two and 21 specific bands were obtained using 100 ISSR and 153 SRAP primers, respectively. The present research could be a valuable tool for identification of Citrus bud sport clones, which laid the foundations for the further study of the mechanisms of Citrus bud sports.Key words: Citrus reticulata Blanco, random amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), simple sequence repeat (SSR), sequence-related amplified polymorphism (SRAP), inter-retrotransposon amplified polymorphism (IRAP), retrotransposon-microsatellite amplified polymorphism (REMAP), identification

LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway

Background/Aims: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. Methods: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. Results: We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. Conclusion: In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment

Global Epidemiology of Dengue Outbreaks in 1990–2015: A Systematic Review and Meta-Analysis

Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted by Aedes mosquitoes. Approximately 50–100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term “dengue outbreak.” In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (both P < 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR = 1.65), suffering from hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53), respectively (all P < 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment

Association Analysis of NLRP3 Inflammation-Related Gene Promotor Methylation as Well as Mediating Effects on T2DM and Vascular Complications in a Southern Han Chinese Population

Objective: To explore the association between the methylation levels in the promoter regions of the NLRP3, AIM2, and ASC genes and T2DM and its vascular complications in a Southern Han Chinese population and further analyze their interaction and mediating effects with environmental factors in T2DM.Methods: A case-control study was used to determine the association between population characteristics, the methylation level in the promoter region of the NLRP3, AIM2, and ASC genes and T2DM and vascular complications. A mediating effect among genes-environment-T2DM and the interaction of gene-gene or gene-environment factors was explored.Results: In the logistic regression model with adjusted covariants, healthy people with lower total methylation levels in the AIM2 promoter region exhibited a 2.29-fold [OR: 2.29 (1.28~6.66), P = 0.011] increased risk of developing T2DM compared with higher-methylation individuals. T2DM patients without any vascular complications who had lower methylation levels (<methylation median) in NLRP3 CpG2 and AIM2 total methylation had 6.45 (OR: 6.45, 95% CI: 1.05~39.78, P = 0.011) and 9.48 (OR: 9.48, 95% CI: 1.14~79.00, P = 0.038) times higher risks, respectively, of developing diabetic microvascular complications than T2DM patients with higher methylation. Similar associations were also found between the lower total methylation of the NLRP3 and AIM2 promoter regions and macrovascular complication risk (NLRP3 OR: 36.03, 95% CI: 3.11~417.06, P = 0.004; AIM2 OR: 30.90, 95% CI: 2.59~368.49, P = 0.007). Lower NLRP3 promoter total methylation was related to a 17.78-fold increased risk of micro-macrovascular complications (OR: 17.78, 95% CI: 2.04~155.28, P = 0.009). Lower ASC CpG1 or CpG3 methylation levels had significant partial mediating effects on T2DM vascular complications caused by higher age (ASC CpG1 explained approximately 52.8% or 32.9% of the mediating effect of age on macrovascular or macro-microvascular complications; ASC CpG3 explained approximately 38.9% of the mediating effect of age on macrovascular complications). No gene-gene or gene-environment interaction was identified in T2DM.Conclusion: Lower levels of AIM2 promoter total methylation might increase the risk of T2DM. NLRP3, AIM2, and ASC promoter total methylation or some CpG methylation loss might increase the risk of T2DM vascular complications, which merits further study to support the robustness of these findings

Investigation on C_f/PyC Interfacial Properties of C/C Composites by the Molecular Dynamics Simulation Method

In this paper, a molecular dynamics (MD) simulation model of carbon-fiber/pyrolytic-carbon (Cf/PyC) interphase in carbon/carbon (C/C) composites manufactured by the chemical vapor phase infiltration (CVI) process was established based on microscopic observation results. By using the MD simulation method, the mechanical properties of the Cf/PyC interphase under tangential shear and a normal tensile load were studied, respectively. Meanwhile, the deformation and failure mechanisms of the interphase were investigated with different sizes of the average length L ¯ a of fiber surface sheets. The empirical formula of the interfacial modulus and strength with the change of L ¯ a was obtained as well. The shear properties of the isotropic pyrolysis carbon (IPyC) matrix were also presented by MD simulation. Finally, the mechanical properties obtained by the MD simulation were substituted into the cohesive force model, and a fiber ejection test of the C/C composite was simulated by the finite element analysis (FEA) method. The simulation results were in good agreement with the experimental ones. The MD simulation results show that the shear performance of the Cf/PyC interphase is relatively higher when L ¯ a is small due to the effects of non-in-plane shear, the barrier between crystals, and long sheet folding. On the other hand, the size of L ¯ a has no obvious influence on the interfacial normal tensile mechanical properties

A comparative study between a late-ripening mutant of citrus and its original line in fruit coloration, sugar and acid metabolism at all fruit maturation stage

Introduction. Fruit color is one of the important external traits that can be used to judge fruit maturation time in citrus. Mutants with different color are useful to study the regulating mechanism of color development. Materials and methods. A new seedless and late-maturing cultivar, ‘Huawan Wuzishatangju’ (HWWZSTJ) (Citrus reticulata Blanco), was selected from ‘Wuzishatangju’ (WZSTJ) through spontaneous bud mutation. Differences in fruit coloration, sugar and acidity contents of the two cultivars were investigated throughout fruit ripening. Results and discussion. Fruit of HWWZSTJ matured in late January to early February, more than 30 days later than WZSTJ. Results from RAPD analysis showed that HWWZSTJ originated from genetic mutation. The chlorophyll, carotenoid, total soluble solid (TSS) and total titratable acidity (TTA) contents of HWWZSTJ were affected by the mutation. Chlorophyll content in peel of HWWZSTJ was significantly higher than that of WZSTJ from November to mid-January while carotenoid content of HWWZSTJ peel was significantly higher than that of WZSTJ throughout fruit maturation. TTA content in HWWZSTJ was significantly higher than that in WZSTJ during early fruit ripening (from Nov. 29 to Dec. 9). Highest TSS (14.1%) was detected in the flesh of WZSTJ in mid-January compared to highest TSS (14.4%) of HWWZSTJ in early February. Conclusion. The mutation in HWWZSTJ detected by RAPD analysis, affected fruit coloration, sugar and acid metabolism, and might be responsible for other late-ripening phenotypes

Plasma-Derived Fibronectin Stimulates Chondrogenic Differentiation of Human Subchondral Cortico-Spongious Progenitor Cells in Late-Stage Osteoarthritis

Migration and chondrogenesis of human subchondral cortico-spongious progenitor cells (SPCs) are the key steps in the repair of microfracture-induced articular cartilage defects. The aim of this study was to evaluate the effect of human plasma-derived fibronectin (Fn) on the chondrogenic differentiation of SPCs, which was isolated from subchondrol cortico-spongious bone of late-stage osteoarthritis (OA) patients. SPCs were isolated and cultured for three passages. Stem cell surface antigens of SPCs were analyzed by flow cytometry. The osteogenic, chondrogenic and adipogenic differentiation potential were detected by histological staining. The chondrogenesis potential of SPCs with or without stimulation of either Fn or BMP-2 were studied by immunochemical staining and gene expression analysis. Cells isolated from subchondral bone presented to be positive for CD44, CD73, CD90, and CD166, and showed high capacity of osteogenic, adipogenic and chondrogenic differentiation, which suggested this cell population to be MSC-like cells. Stimulating with Fn increased the expression of SOX-9, aggrecan, collagen II while decreased the formation of collagen I by immunochemical staining. Gene expression analysis showed similar results. These results suggest that plasma-derived Fn can increase the chondrogenic differentiation of SPCs isolated from late-stage OA and improve cartilage repair after microfracture