Predicting DNA Methylation State of CpG Dinucleotide Using Genome Topological Features and Deep Networks

The hypo- or hyper-methylation of the human genome is one of the epigenetic features of leukemia. However, experimental approaches have only determined the methylation state of a small portion of the human genome. We developed deep learning based (stacked denoising autoencoders, or SdAs) software named DeepMethyl to predict the methylation state of DNA CpG dinucleotides using features inferred from three-dimensional genome topology (based on Hi-C) and DNA sequence patterns. We used the experimental data from immortalised myelogenous leukemia (K562) and healthy lymphoblastoid (GM12878) cell lines to train the learning models and assess prediction performance. We have tested various SdA architectures with different configurations of hidden layer(s) and amount of pre-training data and compared the performance of deep networks relative to support vector machines (SVMs). Using the methylation states of sequentially neighboring regions as one of the learning features, an SdA achieved a blind test accuracy of 89.7% for GM12878 and 88.6% for K562. When the methylation states of sequentially neighboring regions are unknown, the accuracies are 84.82% for GM12878 and 72.01% for K562. We also analyzed the contribution of genome topological features inferred from Hi-C. DeepMethyl can be accessed at http://dna.cs.usm.edu/deepmethyl/

Olmesartan Attenuates the Impairment of Endothelial Cells Induced by Oxidized Low Density Lipoprotein through Downregulating Expression of LOX-1

Oxidized low density lipoprotein (ox-LDL) and its receptor, lectin-Like ox-LDL receptor-1 (LOX-1), play important roles in the development of endothelial injuries. Olmesartan can protect endothelial cells from the impairment caused by various pathological stimulations. In the present study we investigated whether olmesartan decreased the impairment of endothelial cells induced by ox-LDL by exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in mice for 3 weeks led to the remarkable impairment of endothelial cells, including increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK) and expression of apoptotic genes such as B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3. Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly reduced. All these effects, however, were significantly suppressed by the treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1 expression either in cultured endothelial cells or in the aortas of mice, which was reversed with the administration of olmesartan. Our data indicated that olmesartan may attenuate the impairment of endothelial cell via down-regulation of the increased LOX-1 expression induced by ox-LDL

B4SDC: A Blockchain System for Security Data Collection in MANETs

Security-related data collection is an essential part for attack detection and security measurement in Mobile Ad Hoc Networks (MANETs). Due to no fixed infrastructure of MANETs, a detection node playing as a collector should discover available routes to a collection node for data collection. Notably, route discovery suffers from many attacks (e.g., wormhole attack), thus the detection node should also collect securityrelated data during route discovery and analyze these data for determining reliable routes. However, few literatures provide incentives for security-related data collection in MANETs, and thus the detection node might not collect sufficient data, which greatly impacts the accuracy of attack detection and security measurement. In this paper, we propose B4SDC, a blockchain system for security-related data collection in MANETs. Through controlling the scale of RREQ forwarding in route discovery, the collector can constrain its payment and simultaneously make each forwarder of control information (namely RREQs and RREPs) obtain rewards as much as possible to ensure fairness. At the same time, B4SDC avoids collusion attacks with cooperative receipt reporting, and spoofing attacks by adopting a secure digital signature. Based on a novel Proof-of-Stake consensus mechanism by accumulating stakes through message forwarding, B4SDC not only provides incentives for all participating nodes, but also avoids forking and ensures high efficiency and real decentralization at the same time. We analyze B4SDC in terms of incentives and security, and evaluate its performance through simulations. The thorough analysis and experimental results show the efficacy and effectiveness of B4SDC.Peer reviewe

B4SDC: A Blockchain System for Security Data Collection in MANETs

Security-related data collection is an essential part for attack detection and security measurement in Mobile Ad Hoc Networks (MANETs). A detection node (i.e., collector) should discover available routes to a collection node for data collection and collect security-related data during route discovery for determining reliable routes. However, few studies provide incentives for security-related data collection in MANETs. In this paper, we propose B4SDC, a blockchain system for security-related data collection in MANETs. Through controlling the scale of Route REQuest (RREQ) forwarding in route discovery, the collector can constrain its payment and simultaneously make each forwarder of control information (namely RREQs and Route REPlies, in short RREPs) obtain rewards as much as possible to ensure fairness. At the same time, B4SDC avoids collusion attacks with cooperative receipt reporting, and spoofing attacks by adopting a secure digital signature. Based on a novel Proof-of-Stake consensus mechanism by accumulating stakes through message forwarding, B4SDC not only provides incentives for all participating nodes, but also avoids forking and ensures high efficiency and real decentralization. We analyze B4SDC in terms of incentives and security, and evaluate its performance through simulations. The thorough analysis and experimental results show the efficacy and effectiveness of B4SDC.Peer reviewe

Application of Metal–Organic Frameworks (MOFs) in Environmental Biosystems

Metal–organic frameworks (MOFs) are crystalline materials that are formed by self-assembling organic linkers and metal ions with large specific areas and pore volumes. Their chemical tunability, structural diversity, and tailor-ability make them adaptive to decorate many substrate materials, such as biomass-derived carbon materials, and competitive in many environmental biosystems, such as biofuel cells, bioelectrocatalysts, microbial metal reduction, and fermentation systems. In this review, we surmised the recent progress of MOFs and MOF-derived materials and their applications in environmental biosystems. The behavior of MOFs and MOF-derived materials in different environmental biosystems and their influences on performance are described. The inherent mechanisms will guide the rational design of MOF-related materials and lead to a better understanding of their interaction with biocomponents

Elevated serum FGF21 predicts the major adverse cardiovascular events in STEMI patients after emergency percutaneous coronary intervention

Background Although there have been several studies related to serum fibroblast growth factor 21 (FGF21) levels and acute myocardial infarction, the value of serum FGF21 levels in ST-segment elevation myocardial infarction (STEMI) patients after emergency percutaneous coronary intervention (PCI) has not been previously investigated. Methods A total of 348 STEMI patients who underwent emergency PCI were enrolled from January 2016 to December 2018. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), with a median follow-up of 24 months. Eighty patients with stable angina (SA) who underwent selective PCI served as the control group. Serum FGF21 levels were measured by ELISA. Results Serum FGF21 levels were significantly higher in the STEMI group than in the SA group (225.03 ± 37.98 vs. 135.51 ±  34.48, P < 0.001). Multiple linear regression analysis revealed that serum FGF21 levels were correlated with NT-proBNP (P < 0.001). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curve (AUCs) of FGF21 and NT-proBNP were 0.812 and 0.865, respectively. The Kaplan-Meier curves showed that STEMI patients with lower FGF21 levels had an increased MACE-free survival rate. Cox analysis revealed that high FGF21 levels (HR: 2.011, 95% CI: [1.160–3.489]) proved to be a powerful tool in predicting the risk of MACEs among STEMI patients after emergency PCI. Conclusion Elevated FGF21 levels on admission have been shown to be a powerful predictor of MACEs for STEMI patients after emergency PCI

Application of Metal&ndash;Organic Frameworks (MOFs) in Environmental Biosystems

Metal&ndash;organic frameworks (MOFs) are crystalline materials that are formed by self-assembling organic linkers and metal ions with large specific areas and pore volumes. Their chemical tunability, structural diversity, and tailor-ability make them adaptive to decorate many substrate materials, such as biomass-derived carbon materials, and competitive in many environmental biosystems, such as biofuel cells, bioelectrocatalysts, microbial metal reduction, and fermentation systems. In this review, we surmised the recent progress of MOFs and MOF-derived materials and their applications in environmental biosystems. The behavior of MOFs and MOF-derived materials in different environmental biosystems and their influences on performance are described. The inherent mechanisms will guide the rational design of MOF-related materials and lead to a better understanding of their interaction with biocomponents

Ultrathin Films of Organic Networks as Nanofiltration Membranes via Solution-Based Molecular Layer Deposition

Ultrathin films of organic networks on various substrates were fabricated through the solution-based molecular layer deposition (MLD) technique. The rigid tetrahedral geometries of polyfunctional amine and acyl chloride involved in the reaction ensure the continuity of the polymerization process. A linear increase in film thickness with respect to cycle number was observed by UV–vis adsorption, ellipsometry, and quartz crystal microbalance. The growth rate per MLD cycle is 1.6 nm, which can be controlled at the single molecular level. For the first time, we develop the MLD method on the top of hydrolyzed PAN substrate, resulting in nanofiltration (NF) membranes. The stepwise growth was monitored via attenuated total reflectance infrared studies. The separation performance of the obtained membrane for various solutes was sensitive to the terminated layers and number of cycles. The rejection of NH₂-terminated membranes follows the order of CaCl₂ > Na₂SO₄ > NaCl, while the order for COOH-capped surface is Na₂SO₄ > CaCl₂ > NaCl. The absolute value of zeta potential for the MLD membranes decreases with the addition of deposition layers. The moderate water flux for the resulting membrane is due to the reduced porosity of the support as well as the low roughness and hydrophilicity of the membrane surface. This bottom-up process provides a promising approach for construction of long-term steady NF membranes with nanoscale dimensions

Aberrant Epigenetic Gene Regulation in Lymphoid Malignancies

In lymphoid malignancies, aberrant epigenetic mechanisms such as DNA methylation and histone modifications influence chromatin architecture and can result in altered gene expression. These alterations commonly affect genes that play important roles in the cell cycle, apoptosis, and DNA repair in non-Hodgkin lymphoma (NHL). The ability to identify epigenetic modifications to these important genes has increased exponentially due to advances in technology. As a result, there are well-defined, gene-specific epigenetic aberrations associated with NHL comprising follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and diffuse large B-cell lymphoma (DLBCL). The identification of these genes is important because they may be used as biomarkers for prognosis, diagnosis and in developing improved treatment strategies. Also important, in the control of gene expression, is the packaging of DNA within the nucleus of a cell. This packaging can be distorted by epigenetic alterations and may alter the accessibility of certain regions of the genome in cancer cells. This review discusses the impact of known epigenetic aberration on the regulation of gene expression in NHL and provides insight into the spatial conformation of the genome (DNA packaging) in acute lymphoblastic leukemia