254 research outputs found
McCLS: Certificateless Signature Scheme for Emergency Mobile Wireless Cyber-Physical Systems
Mobile Ad Hoc Network is a self-configurable and self-organizing wireless network of mobile devices without fixed infrastructure support, which makes it a good candidate as underlying communication network for the Cyber-Physical Systems in emergency conditions such as earthquake, flood, and battlefields. In these scenarios, efficient communication schemes with security support are especially desired. Two cryptography approaches, the public key cryptography and the identitybased cryptography, face the costly and complex key management problem and the âkey escrow" problem in the real-life deployment. Recently, the certificateless public key cryptography (CL-PKC) was introduced to address these problems in previous approaches. However, the efficiency of the schemes based on CL-PKC is not high and can be improved further. In this paper, we present an improved certificateless signature scheme (McCLS) based on bilinear pairings. First, we theoretically compare the efficiency of McCLS with that of existing certificateless signature schemes (CLS). Second, an empirical study is conducted to compare the traditional AODV with the McCLS scheme based on AODV (McDV) in their efficiency and effectiveness against two most common attacks (i.e. redirection attack and rushing attack). Results from theoretical analysis show that the new McCLS scheme is more efficient than existing CLS solutions, and results from empirical studies show that the McDV is able to resist the two common attacks without causing substantial degradation of the network performance
Metabolomics revealed the toxicity of cationic liposomes in HepG2 cells using UHPLCâQâTOF/MS and multivariate data analysis
Cationic liposomes (CLs) are novel nonviral vectors widely used for delivering drugs or genes. However, applications of CLs are largely hampered by their cytotoxicity, partly because the potential mechanism underlying the cytotoxicity of CLs remains unclear. The aim of the present study was to explore the underlying mechanism of cytotoxicity induced by CLs on HepG2 cells. Differential metabolites were identified and quantified using ultraâliquid chromatography quadrupole timeâofâflight mass spectrometry (UHPLCâQâTOF/MS). The toxicity of CLs on HepG2 cells was evaluated by multivariate data analysis and statistics. Additionally, CCKâ8 assay, heatmap, pathway and coâexpression network were carried out to explore the relations between the metabolites and the pathways. The results showed a doseâdependent toxic effect of CLs on HepG2 cells, with an IC50 value of 119.9âÎŒg/mL. Multivariate statistical analysis identified 42 potential metabolites between CLs exposure and control groups. Pathway analysis showed significant changes in pathways involving amino acid metabolism, energy metabolism, lipid metabolism and oxidative stress in the CLs exposure group vs the control group. Metabolites related to the aboveâmentioned pathways included phenylalanine, methionine, creatine, oxalacetic acid, glutathione, oxidized glutathione, choline phosphate and several unsaturated fatty acids, indicating that cells were disturbed in amino acid metabolism, energy and lipid supply when CLs exposureâinduced injury occurred. It is concluded that CLs may induce cytotoxicity by enhancing reactive oxygen species in vitro, affect the normal process of energy metabolism, disturb several vital signaling pathways and finally induce cell death.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139913/1/bmc4036.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139913/2/bmc4036_am.pd
Evolutionary History and Phylodynamics of Influenza A and B Neuraminidase (NA) Genes Inferred from Large- Scale Sequence Analyses
Background: Influenza neuraminidase (NA) is an important surface glycoprotein and plays a vital role in viral replication and drug development. The NA is found in influenza A and B viruses, with nine subtypes classified in influenza A. The complete knowledge of influenza NA evolutionary history and phylodynamics, although critical for the prevention and control of influenza epidemics and pandemics, remains lacking.
Methodology/Principal findings: Evolutionary and phylogenetic analyses of influenza NA sequences using Maximum Likelihood and Bayesian MCMC methods demonstrated that the divergence of influenza viruses into types A and B occurred earlier than the divergence of influenza A NA subtypes. Twenty-three lineages were identified within influenza A, two lineages were classified within influenza B, and most lineages were specific to host, subtype or geographical location. Interestingly, evolutionary rates vary not only among lineages but also among branches within lineages. The estimated tMRCAs of influenza lineages suggest that the viruses of different lineages emerge several months or even years before their initial detection. The dN/dS ratios ranged from 0.062 to 0.313 for influenza A lineages, and 0.257 to 0.259 for influenza B lineages. Structural analyses revealed that all positively selected sites are at the surface of the NA protein, with a number of sites found to be important for host antibody and drug binding.
Conclusions/Significance: The divergence into influenza type A and B from a putative ancestral NA was followed by the divergence of type A into nine NA subtypes, of which 23 lineages subsequently diverged. This study provides a better understanding of influenza NA lineages and their evolutionary dynamics, which may facilitate early detection of newly emerging influenza viruses and thus improve influenza surveillance
Experimental Investigation on Thermal Management of Electric Vehicle Battery Module with Paraffin/Expanded Graphite Composite Phase Change Material
The temperature has to be controlled adequately to maintain the electric vehicles (EVs) within a safety range. Using paraffin as the heat dissipation source to control the temperature rise is developed. And the expanded graphite (EG) is applied to improve the thermal conductivity. In this study, the paraffin and EG composite phase change material (PCM) was prepared and characterized. And then, the composite PCM have been applied in the 42110 LiFePO4 battery module (48âV/10âAh) for experimental research. Different discharge rate and pulse experiments were carried out at various working conditions, including room temperature (25°C), high temperature (35°C), and low temperature (â20°C). Furthermore, in order to obtain the practical loading test data, a battery pack with the similar specifications by 2Sâ2P with PCM-based modules were installed in the EVs for various practical road experiments including the flat ground, 5°, 10°, and 20° slope. Testing results indicated that the PCM cooling system can control the peak temperature under 42°C and balance the maximum temperature difference within 5°C. Even in extreme high-discharge pulse current process, peak temperature can be controlled within 50°C. The aforementioned results exhibit that PCM cooling in battery thermal management has promising advantages over traditional air cooling
Tumor-associated microglia and macrophages in glioblastoma: From basic insights to therapeutic opportunities
Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Currently, the standard treatment of glioblastoma includes surgery, radiotherapy, and chemotherapy. Despite aggressive treatment, the median survival is only 15 months. GBM progression and therapeutic resistance are the results of the complex interactions between tumor cells and tumor microenvironment (TME). TME consists of several different cell types, such as stromal cells, endothelial cells and immune cells. Although GBM has the immunologically âcoldâ characteristic with very little lymphocyte infiltration, the TME of GBM can contain more than 30% of tumor-associated microglia and macrophages (TAMs). TAMs can release cytokines and growth factors to promote tumor proliferation, survival and metastasis progression as well as inhibit the function of immune cells. Thus, TAMs are logical therapeutic targets for GBM. In this review, we discussed the characteristics and functions of the TAMs and evaluated the state of the art of TAMs-targeting strategies in GBM. This review helps to understand how TAMs promote GBM progression and summarizes the present therapeutic interventions to target TAMs. It will possibly pave the way for new immune therapeutic avenues for GBM patients
Identification and validation of cuproptosis-related genes in acetaminophen-induced liver injury using bioinformatics analysis and machine learning
BackgroundAcetaminophen (APAP) is commonly used as an antipyretic analgesic. However, acetaminophen overdose may contribute to liver injury and even liver failure. Acetaminophen-induced liver injury (AILI) is closely related to mitochondrial oxidative stress and dysfunction, which play critical roles in cuproptosis. Here, we explored the potential role of cuproptosis-related genes (CRGs) in AILI.MethodsThe gene expression profiles were obtained from the Gene Expression Omnibus database. The differential expression of CRGs was determined between the AILI and control samples. Protein protein interaction, correlation, and functional enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was evaluated. The AILI mouse model was established by intraperitoneal injection of APAP solution. Quantitative real-time PCR and western blotting were used to validate hub gene expression in the AILI mouse model. The copper content in the mouse liver samples and AML12 cells were quantified using a colorimetric assay kit. Ammonium tetrathiomolybdate (ATTM), was administered to mouse models and AML12 cells in order to investigate the effects of copper chelator on AILI.ResultsThe analysis identified 7,809 differentially expressed genes, 4,245 of which were downregulated and 3,564 of which were upregulated. Four optimal feature genes (OFGs; SDHB, PDHA1, NDUFB2, and NDUFB6) were identified through the intersection of two machine learning algorithms. Further nomogram, decision curve, and calibration curve analyses confirmed the diagnostic predictive efficacy of the four OFGs. Enrichment analysis indicated that the OFGs were involved in multiple pathways, such as IL-17 pathway and chemokine signaling pathway, that are related to AILI progression. Immune infiltration analysis revealed that macrophages were more abundant in AILI than in control samples, whereas eosinophils and endothelial cells were less abundant. Subsequently, the AILI mouse model was successfully established, and histopathological analysis using hematoxylinâeosin staining along with liver function tests revealed a significant induction of liver injury in the APAP group. Consistent with expectations, both mRNA and protein levels of the four OFGs exhibited a substantial decrease. The administration of ATTAM effectively mitigates copper elevation induced by APAP in both mouse model and AML12 cells. However, systemic administration of ATTM did not significantly alleviate AILI in the mouse model.ConclusionThis study first revealed the potential role of CRGs in the pathological process of AILI and offered novel insights into its underlying pathogenesis
Antibacterial, injectable, and adhesive hydrogel promotes skin healing
With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5Â wt% CMCS aqueous solution and 5Â wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 Ă 107Â CFU/mL in the blank group and 2.5 Ă 107Â CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 Ă 107Â CFU/mL in the blank group and 8.5 Ă 107Â CFU/mL in the 5/5 CPH group), and certain adhesion (0.71Â kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14Â days in the 5/5 CPH group) and repair of cells with broad application prospects
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