Identification and characterization of nucleotide metabolism and neuroendocrine regulation-associated modification patterns in stomach adenocarcinoma with auxiliary prognostic assessment and immunotherapy response prediction

BackgroundThe significance of nucleotide metabolism and neuroendocrine in cellular immune response and cancer is becoming more well-established. However, the mechanisms underlying nucleotide metabolism and neuroendocrine involvement in stomach adenocarcinoma (STAD) remain unclear.MethodsFirst, a pan-cancer overview of nucleotide metabolism and neuroendocrine-related genes (NMNGs) was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. We next extensively assessed variations in prognosis and tumor microenvironment (TME) features across the various modification patterns, based on an extensive analysis of the NMNG modification patterns of 808 STAD samples based on 46 NMNGs. Utilizing principal component analysis methodologies, the NMNGscore was developed to measure NMNG alteration patterns of individual tumors.ResultsPan-cancer analysis shows that NMNGs mostly act as risk genes in multiple cancer types, especially in STAD. Based on the NMNGs we detected two different NMNG modification patterns in STAD. Both patterns showed distinct immune cell infiltration features and biological behavior, with NMNGcluster A exhibiting a worse prognosis and a larger amount of immune infiltration. Differentially expressed genes with prognostic relevance were used to classify the STAD samples into three genomic subgroups. Analysis of survival rates revealed that cluster B genes were associated with longer life expectancy than clusters A and C. Individual STAD patients’ NMNG alteration patterns were analyzed by analyzing their NMNGscore signatures. NMNGscore and immune cells showed a statistically significant adverse correlation with each other. Increased longevity, a higher incidence of mutations, and a better response to immunotherapy were associated with patients’ NMNG scores.ConclusionsOur findings provide a personalized prediction tool for prognosis and immunotherapy sensitivity in patients, as well as a promising knowledge of nucleotide metabolism and neuroendocrine in STAD

Genetic analysis of chikungunya viruses imported to mainland China in 2008

<p>Abstract</p> <p>Background</p> <p>Chikungunya virus (CHIKV) has caused large outbreaks worldwide in recent years, especially on the islands of the Indian Ocean and India. The virus is transmitted by mosquitoes (<it>Aedes aegypti</it>), which are widespread in China, with an especially high population density in southern China. Analyses of full-length viral sequences revealed the acquisition of a single adaptive mutation providing a selective advantage for the transmission of CHIKV by this species. No outbreaks due to the local transmission of CHIKV have been reported in China, and no cases of importation were detected on mainland China before 2008. We followed the spread of imported CHIKV in southern China and analyzed the genetic character of the detected viruses to evaluate their potential for evolution.</p> <p>Results</p> <p>The importation of CHIKV to mainland China was first detected in 2008. The genomic sequences of four of the imported viruses were identified, and phylogenetic analysis demonstrated that the sequences were clustered in the Indian Ocean group; however, seven amino acid changes were detected in the nonstructural protein-coding region, and five amino acid changes were noted in the structural protein-coding regions. In particular, a novel substitution in E2 was detected (K252Q), which may impact the neurovirulence of CHIKV. The adaptive mutation A226V in E1 was observed in two imported cases of chikungunya disease.</p> <p>Conclusions</p> <p>Laboratory-confirmed CHIKV infections among travelers visiting China in 2008 were presented, new mutations in the viral nucleic acids and proteins may represent adaptive mutations for human or mosquito hosts.</p

A nomogram based on collagen signature for predicting the immunoscore in colorectal cancer

ObjectivesThe Immunoscore can categorize patients into high- and low-risk groups for prognostication in colorectal cancer (CRC). Collagen plays an important role in immunomodulatory functions in the tumor microenvironment (TME). However, the correlation between collagen and the Immunoscore in the TME is unclear. This study aimed to construct a collagen signature to illuminate the relationship between collagen structure and Immunoscore.MethodsA total of 327 consecutive patients with stage I-III stage CRC were included in a training cohort. The fully quantitative collagen features were extracted at the tumor center and invasive margin of the specimens using multiphoton imaging. LASSO regression was applied to construct the collagen signature. The association of the collagen signature with Immunoscore was assessed. A collagen nomogram was developed by incorporating the collagen signature and clinicopathological predictors after multivariable logistic regression. The performance of the collagen nomogram was evaluated via calibration, discrimination, and clinical usefulness and then tested in an independent validation cohort. The prognostic values of the collagen nomogram were assessed using Cox regression and the Kaplan−Meier method.ResultsThe collagen signature was constructed based on 16 collagen features, which included 6 collagen features from the tumor center and 10 collagen features from the invasive margin. Patients with a high collagen signature were more likely to show a low Immunoscore (Lo IS) in both cohorts (P&lt;0.001). A collagen nomogram integrating the collagen signature and clinicopathological predictors was developed. The collagen nomogram yielded satisfactory discrimination and calibration, with an AUC of 0.925 (95% CI: 0.895-0.956) in the training cohort and 0.911 (95% CI: 0.872-0.949) in the validation cohort. Decision curve analysis confirmed that the collagen nomogram was clinically useful. Furthermore, the collagen nomogram-predicted subgroup was significantly associated with prognosis. Moreover, patients with a low-probability Lo IS, rather than a high-probability Lo IS, could benefit from chemotherapy in high-risk stage II and stage III CRC patients.ConclusionsThe collagen signature is significantly associated with the Immunoscore in the TME, and the collagen nomogram has the potential to individualize the prediction of the Immunoscore and identify CRC patients who could benefit from adjuvant chemotherapy

Rapid, Specific Detection of Alphaviruses from Tissue Cultures Using a Replicon-Defective Reporter Gene Assay

We established a rapid, specific technique for detecting alphaviruses using a replicon-defective reporter gene assay derived from the Sindbis virus XJ-160. The pVaXJ expression vector containing the XJ-160 genome was engineered to form the expression vectors pVaXJ-EGFP expressing enhanced green fluorescence protein (EGFP) or pVaXJ-GLuc expressing Gaussia luciferase (GLuc). The replicon-defective reporter plasmids pVaXJ-EGFPΔnsp4 and pVaXJ-GLucΔnsp4 were constructed by deleting 1139 bp in the non-structural protein 4 (nsP4) gene. The deletion in the nsP4 gene prevented the defective replicons from replicating and expressing reporter genes in transfected BHK-21 cells. However, when these transfected cells were infected with an alphavirus, the non-structural proteins expressed by the alphavirus could act on the defective replicons in trans and induce the expression of the reporter genes. The replicon-defective plasmids were used to visualize the presence of alphavirus qualitatively or detect it quantitatively. Specificity tests showed that this assay could detect a variety of alphaviruses from tissue cultures, while other RNA viruses, such as Japanese encephalitis virus and Tahyna virus, gave negative results with this system. Sensitivity tests showed that the limit of detection (LOD) of this replicon-defective assay is between 1 and 10 PFU for Sindbis viruses. These results indicate that, with the help of the replicon-defective alphavirus detection technique, we can specifically, sensitively, and rapidly detect alphaviruses in tissue cultures. The detection technique constructed here may be well suited for use in clinical examination and epidemiological surveillance, as well as for rapid screening of potential viral biological warfare agents

Photoluminescent and superparamagnetic reduced graphene oxide-iron oxide quantum dots for dual-modality imaging, drug delivery and photothermal therapy

Reduced graphene oxide–iron oxide quantum dots (QDs) with intrinsic photoluminescent and superparamagnetic properties were synthesized through a green, hydrothermal method that simultaneously reduced and shattered graphene nanosheets to form the dots. The structure, morphology, properties and cell viability of these QDs were investigated. The QDs emitted violet light when excited at 320 nm, possessed no residual magnetization upon magnetic hysteresis tests, and had low cytotoxicity to healthy cells at low concentrations. The suitability of the QDs for fluorescent and magnetic resonance dual-modality imaging was shown by in vitro imaging with dermal fibroblast cells and T2 relaxation time. A drug could be loaded onto the surface of the QDs, with a loading ratio of drug to QD of 0.31:1. The drug achieved a steady but full release from the QDs over 8 h: these drug-loaded QDs could be manipulated by an external magnetic stimulation for targeted drug delivery. The potential for use as a cancer photothermal therapy was demonstrated by both a rapid, ∼50 °C temperature increase by a suspension of 100 μg ml−1 of QDs and the photothermal ablation of HeLa cells in vitro under near infrared irradiation. The stability of the MGQDs in fetal calf serum was shown to improve when an ionic drug was coated on the surface

2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV

Fault Diagnosis Method of DC Charging Points for EVs Based on Deep Belief Network

According to the complex fault mechanism of direct current (DC) charging points for electric vehicles (EVs) and the poor application effect of traditional fault diagnosis methods, a new kind of fault diagnosis method for DC charging points for EVs based on deep belief network (DBN) is proposed, which combines the advantages of DBN in feature extraction and processing nonlinear data. This method utilizes the actual measurement data of the charging points to realize the unsupervised feature extraction and parameter fine-tuning of the network, and builds the deep network model to complete the accurate fault diagnosis of the charging points. The effectiveness of this method is examined by comparing with the backpropagation neural network, radial basis function neural network, support vector machine, and convolutional neural network in terms of accuracy and model convergence time. The experimental results prove that the proposed method has a higher fault diagnosis accuracy than the above fault diagnosis methods

Tuning Magnetic Microstructures of Reference Layer in Magnetic Tunneling Junctions

Magnetic microstructures in the reference layer in magnetic tunneling junctions (MTJs) are tuned by a reversal field under ambient conditions to investigate their effects on the magnetoresistance (MR) and the exchange coupling field (HE) between the reference layer and the free layer. Magnetization changes in the reference layer can be probed by measuring minor MR loops. The results show the HE of the minor MR loops versus the applied reversal field changes from negative to positive and crosses zero. These results can be explained by the magnetic inhomogeneities at the interface between anti-ferromagnetic/pinned-ferromagnetic layers, which causes the partial magnetization reversal in the reference layer