Development of novel monoclonal antibodies for blocking NF-κB activation induced by CD2v protein in African swine fever virus.

Background: CD2v, a critical outer envelope glycoprotein of the African swine fever virus (ASFV), plays a central role in the hemadsorption phenomenon during ASFV infection and is recognized as an essential immunoprotective protein. Monoclonal antibodies (mAbs) targeting CD2v have demonstrated promise in both diagnosing and combating African swine fever (ASF). The objective of this study was to develop specific monoclonal antibodies against CD2v. Methods: In this investigation, Recombinant CD2v was expressed in eukaryotic cells, and murine mAbs were generated through meticulous screening and hybridoma cloning. Various techniques, including indirect enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence assay (IFA), and bio-layer interferometry (BLI), were employed to characterize the mAbs. Epitope mapping was conducted using truncation mutants and epitope peptide mapping. Results: An optimal antibody pair for a highly sensitive sandwich ELISA was identified, and the antigenic structures recognized by the mAbs were elucidated. Two linear epitopes highly conserved in ASFV genotype II strains, particularly in Chinese endemic strains, were identified, along with a unique glycosylated epitope. Three mAbs, 2B25, 3G25, and 8G1, effectively blocked CD2v-induced NF-κB activation. Conclusions: This study provides valuable insights into the antigenic structure of ASFV CD2v. The mAbs obtained in this study hold great potential for use in the development of ASF diagnostic strategies, and the identified epitopes may contribute to vaccine development against ASFV.

Causal association between gut microbiota and fibromyalgia: a Mendelian randomization study.

Background: Fibromyalgia (FM) is a syndrome characterized by chronic and widespread musculoskeletal pain. A number of studies have implied a potential association between gut microbiota and FM. However, the casual association between gut microbiota and FM remains unknown. Method: Mendelian randomization (MR) study was conducted using the summary statistics of genetic variants from the genome-wide association study (GWAS). Inverse variance weighted (IVW), combined with MR-Egger and weighted median were used to investigate the causal association between 119 gut microbiota genera and FM. Sensitivity analyses were performed on the MR results, including heterogeneity test, leave-one-out test and pleiotropy test. Results: A total of 1,295 single nucleotide polymorphism (SNPs) were selected as instrumental variables (IVs), with no significant heterogeneity and pleiotropy according to the sensitivity analyses. Five gut microbiota genera were found to have significant casual association with FM. Coprococcus2 (OR = 2.317, p-value = 0.005, 95% CI: 1.289-4.167), Eggerthella (OR = 1.897, p-value = 0.001, 95% CI: 1.313-2.741) and Lactobacillus (OR = 1.576, p-value =0.020, 95% CI: 1.073-2.315) can increase the risk of FM. FamillyXIIIUCG001 (OR = 0.528, p-value = 0.038, 95% CI: 0.289-0.964) and Olsenella (OR = 0.747, p-value = 0.050, 95% CI: 0.557-1.000) can decrease the risk of FM. Conclusion: This MR study found that gut microbiota is casually associated with FM. New insights into the mechanisms of FM mediated by gut microbiota are provided.

Data-Driven and Machine-Learning Methods to Project Coronavirus Disease 2019 Pandemic Trend in Eastern Mediterranean.

Background: The coronavirus disease 2019 (COVID-19) pandemic has become a major public health crisis worldwide, and the Eastern Mediterranean is one of the most affected areas. Materials and Methods: We use a data-driven approach to assess the characteristics, situation, prevalence, and current intervention actions of the COVID-19 pandemic. We establish a spatial model of the spread of the COVID-19 pandemic to project the trend and time distribution of the total confirmed cases and growth rate of daily confirmed cases based on the current intervention actions. Results: The results show that the number of daily confirmed cases, number of active cases, or growth rate of daily confirmed cases of COVID-19 are exhibiting a significant downward trend in Qatar, Egypt, Pakistan, and Saudi Arabia under the current interventions, although the total number of confirmed cases and deaths is still increasing. However, it is predicted that the number of total confirmed cases and active cases in Iran and Iraq may continue to increase. Conclusion: The COVID-19 pandemic in Qatar, Egypt, Pakistan, and Saudi Arabia will be largely contained if interventions are maintained or tightened. The future is not optimistic, and the intervention response must be further strengthened in Iran and Iraq. The aim of this study is to contribute to the prevention and control of the COVID-19 pandemic.

Identification of Potential Key Agents for Targeting RNA-Dependent RNA Polymerase of SARS-CoV-2 by Integrated Analysis and Virtual Drug Screening.

BACKGROUND: RNA-dependent RNA polymerase (RdRp) is the key enzyme responsible for the SARS-CoV-2 replication process and catalyzes the synthesis of complementary minus strand RNA and genomic plus strand RNA, often recognized as good targets for antiviral drugs. MATERIALS AND METHODS: A systematic screening of existing antiviral compounds, family analysis, conserved domain analysis, three-dimensional structure modeling, drug virtual screening, and bioassays were performed to identify agents that potentially targeted RNA-dependent RNA polymerase of SARS-CoV-2. RESULTS: Four thousand nine hundred and forty seven antiviral lead compounds were selected and evaluated by systematic screening. Of these, 359 agents were screened by family analysis and conserved domain analysis. They were further analyzed by three-dimensional structure modeling, virtual drug screening, and bioassays. The results identified 102 agents with potential for repurposing to target the RNA-dependent RNA polymerase of SARS-CoV-2. CONCLUSION: This study identified 102 key agents with potential anti-SARS-CoV-2 RNA-dependent RNA polymerase function and prospects of rapid clinical application for the treatment of COVID-19.

Identification of Potential Key Genes for Pathogenesis and Prognosis in Prostate Cancer by Integrated Analysis of Gene Expression Profiles and the Cancer Genome Atlas.

Background: Prostate cancer (PCa)is a malignancy of the urinary system with a high incidence, which is the second most common male cancer in the world. There are still huge challenges in the treatment of prostate cancer. It is urgent to screen out potential key biomarkers for the pathogenesis and prognosis of PCa. Methods: Multiple gene differential expression profile datasets of PCa tissues and normal prostate tissues were integrated analysis by R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the overlapping Differentially Expressed Genes (DEG) were performed. The STRING online database was used in conjunction with Cytospace software for protein-protein interaction (PPI) network analysis to define hub genes. The relative mRNA expression of hub genes was detected in Gene Expression Profiling Interactive Analysis (GEPIA) database. A prognostic gene signature was identified by Univariate and multivariate Cox regression analysis. Results: Three hundred twelve up-regulated genes and 85 down-regulated genes were identified from three gene expression profiles (GSE69223, GSE3325, GSE55945) and The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset. Seven hub genes (FGF2, FLNA, FLNC, VCL, CAV1, ACTC1, and MYLK) further were detected, which related to the pathogenesis of PCa. Seven prognostic genes (BCO1, BAIAP2L2, C7, AP000844.2, ASB9, MKI67P1, and TMEM272) were screened to construct a prognostic gene signature, which shows good predictive power for survival by the ROC curve analysis. Conclusions: We identified a robust set of new potential key genes in PCa, which would provide reliable biomarkers for early diagnosis and prognosis and would promote molecular targeting therapy for PCa.

A Meta-Analysis of Neuron-Specific Enolase Levels in Cerebrospinal Fluid and Serum in Children With Epilepsy.

Background: Studies suggest that neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF) and serum play an important role in childhood epilepsy. However, these investigations remain controversial due to inconsistent clinical results. The present study aimed to quantitatively summarize and assess whether CSF and serum NSE levels are associated with epilepsy in children. Methods : A systematic search of the Harvard Hollis+, Clinicaltrials, Open Gray, China National Knowledge Infrastructure, and Wanfang databases was performed. Studies investigating NSE and epilepsy were identified and retrieved. Original studies with data overlapping those from other investigations and those lacking the necessary data were excluded. The included studies were extracted and synthesized, and data were analyzed using a random-effects model in R Studio and Comprehensive Meta-Analysis version 3 (Biostat, Englewood, NJ, USA). Results: Random-effects meta-analysis of 26 studies, including 1,360 patients, and 1,256 healthy control, revealed that childhood epilepsy exhibited meaningfully increased CSF and serum levels of NSE compared with controls [Hedges' g = 1.962 (95% confidence interval, 1.413-2.512); P < 0.001]. No single study meaningfully influenced the overall association between CSF and serum levels of NSE and epilepsy after sensitivity analysis. Subgroup analyses according to sample source and assay type revealed a significant association between NSE levels and epilepsy. Stratified analysis confirmed that NSE levels were significantly correlated with the severity of neurological compromise. Metaregression analyses revealed that sample size, mean age, and sex may contribute to effect-size reductions; however, sample source, assay type, and country did not moderate effect size. Funnel plots constructed using the trim-and-fill method confirmed that the outcome of the meta-analysis could not be due to publication bias. Conclusion: The results demonstrated that childhood epilepsy exhibits significantly elevated levels of NSE in the CSF and serum, thus strengthening the association between increased NSE levels and epilepsy.

Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study.

Importance: Accumulating evidence suggests that serum levels of S100B may play a role in epilepsy. Objective: We performed a meta-analysis to quantitatively summarize the serum S100B data available for patients with epilepsy. Data source: Two independent researchers conducted a systematic investigation of the Harvard Hollis+, Open Gray, Clinicaltrials, Wanfangdata, and CNKI databases through Dec 6, 2018, for all studies published in English and Chinese. The search terms included S100B and calcium-binding protein B in combination with epilepsy. Study selection: Original studies and reported data from these search terms are included. Studies where data overlapped with other studies were excluded. Data extraction and synthesis: investigators extracted, pooled and analyzed data from the included studies using a fixed-effects model in the Comprehensive Meta-Analysis3.3 and R software. Main outcomes and measures: Peripheral blood levels of S100B in patients with epilepsy compared with controls. Aberrations in peripheral blood levels of S100B were hypothesized to be related to epilepsy. Results: a fixed-effects meta-analysis of all 18 studies, including 1,057 unique participants, indicated that patients with epilepsy had significantly increased peripheral blood levels of S100B compared to controls (Hedges g = 1.568, 95% CI =1.431-1.706, P < 0.001). Sensitivity analysis showed that no single study significantly influenced the overall association of peripheral blood levels of S100B and epilepsy. Most of the subgroup analyses, including those of country, assay type and publication language, demonstrated a statistically significant association between peripheral blood levels of S100B and epilepsy. Meta-regression analyses indicated that gender (regression coefficient [SE], -0.2524 [0.0641]; 95%CI, -0.3781 to -0.1267; P = 0.0001) and mean age (regression coefficient [SE], -0.1224 [0.0426]; 95% CI, -0.2058 to -0.0390; P = 0.0040) might present serum S100B reductions, but sample size, years, assay type, publication language and country did not show moderating effects on the effect sizes. Furthermore, the trim-and-fill method used to adjust for funnel plot asymmetry in our meta-analysis confirmed that a positive outcome is unlikely to be due to publication bias. Conclusion and relevance: the results of this meta-analysis provide evidence for a significant increase in serum S100B levels in patients with epilepsy. Serum S100B is the most worthwhile biomarker of epilepsy, which is helpful for the clinical diagnosis and prognosis of epilepsy.