SRP54 of black carp negatively regulates MDA5-mediated antiviral innate immunity.

Signal Recognition Particle 54 kDa (SRP54) is a subunit of the signal recognition particle (SRP), a cytoplasmic ribonucleoprotein complex guiding the transportation of newly synthesized proteins from polyribosomes to endoplasmic reticulum. In mammals, it has been reported to regulate the RLR signaling pathway negatively by impairing the association between MAVS and MDA5/RIG-I. However, the role of SRP54 in teleost antiviral innate immune response remains obscure. In this study, the SRP54 homolog of black carp (bcSRP54) has been cloned, and its function in antiviral innate immunity has been elucidated. The CDS of bcSRP54 gene consists of 1515 nucleotides and encodes 504 amino acids. Immunofluorescence (IF) showed that bcSRP54 was mainly distributed in the cytoplasm. Overexpressed bcSRP54 significantly reduced bcMDA5-mediated transcription of interferon (IFN) promoter in reporter assay. Co-expression of bcSRP54 and bcMDA5 significantly suppressed bcMDA5-mediated IFN signaling and antiviral activity, while bcSRP54 knockdown increased the antiviral ability of host cells. In addition, the results of the immunofluorescence staining demonstrated the subcellular overlapping between bcSRP54 and bcMDA5, and the co-immunoprecipitation (co-IP) experiment identified their association. Furthermore, the over-expression of bcSRP54 did not influence the protein expression and ubiquitination modification level of bcMDA5, however, hindered the binding of bcMDA5 to bcMAVS. In summary, our results conclude that bcSRP54 targets bcMDA5 and inhibits the interaction between bcMDA5 and bcMAVS, thereby negatively regulating antiviral innate immunity, which provides insight into how teleost SRP54 regulates IFN signaling.

Association between glucose levels at admission and outcomes of pneumonia: a systematic review and meta-analysis.

BACKGROUND: Elevated blood glucose at hospital admission is frequently observed and has been associated with adverse outcomes in various patient populations. This meta-analysis sought to consolidate existing evidence to assess the association between elevated blood glucose at admission and clinical outcomes amongst pneumonia patients. METHODS: We searched PubMed, Medline, Cochrane library, Web of Science (WoS), and Scopus databases for studies, published up to 31 August 2023, and reporting on the clinical outcomes and the blood glucose levels at admission. Data were extracted by two independent reviewers. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% confidence intervals (CI) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes. RESULTS: A total of 23 studies with 34,000 participants were included. Elevated blood glucose at admission was significantly associated with increased short-term (pooled OR: 2.67; 95%CI: 1.73-4.12) and long-term mortality (pooled OR: 1.70; 95%CI: 1.20-2.42). Patients with raised glucose levels were more likely to require ICU admission (pooled OR: 1.86; 95%CI: 1.31-2.64). Trends also suggested increased risks for hospital readmission and mechanical ventilation, though these were not statistically significant. Elevated blood glucose was linked with approximately 0.72 days longer duration of hospital stay. CONCLUSION: Elevated blood glucose level at the time of hospital admission is associated with several adverse clinical outcomes, especially mortality, in patients with pneumonia. These findings underscore the importance of recognizing hyperglycemia as significant prognostic marker in pneumonia patients. Further research is needed to determine whether targeted interventions to control glucose levels can improve these outcomes.

Wastewater treatment and emerging contaminants: Bibliometric analysis.

In recent years, emerging contaminants have been found in the wastewater, surface water, and even drinking water, which should be treated to ensure the safety of our living environment. In this study, we provide a comprehensive summary of wastewater treatment and emerging contaminants research from 1998 to 2021 by using the bibliometric analysis. This study is conducted based on the Web of Science Core Collection Database. The bibliometix R-package, VOSviewer and CiteSpace software are used for bibliometric analysis and science mapping. A dataset of 10, 605 publications has been retrieved. The analysis results show that China has produced the most publications. China and the United States have the closest cooperation. Analysis of the most cited papers reveals that the purification or removal techniques such as ozonation or membrane filtration can effectively remove pharmaceutical compounds from the water environment. We also found that the efficient detection of emerging contaminants and the optimization of removal methods are current challenges. Finally, future research directions are discussed.

Activation of Topological Defects Induces a Brittle-to-Ductile Transition in Epithelial Monolayers.

Epithelial monolayers are subjected to various mechanical forces, such as stretching, shearing, and compression. Thus, its mechanical response to external loadings is essential for its biological functions. However, the mechanism of the fracture failure of the epithelial monolayer remains poorly understood. Here, by introducing a new type of topological transition, i.e., detach transition or T4 transition, we develop a modified cellular vertex model to investigate the rupture of the cell monolayer. Interestingly, we find a brittle-to-ductile transition in epithelial monolayers, which is controlled by the mechanical properties of single cells and cell-cell contacts. We reveal that the external loadings can activate cell rearrangement in ductile cell monolayers. The plastic deformation results from the nucleation and propagation of "pentagon-heptagon defects" in analogy with the topological defects commonly seen in 2D materials. By using a simplified four-cell model, we further demonstrate that the brittle-to-ductile transition is induced by the competition between cell rearrangement and cell detachment. Our work provides a new theoretical framework to study the rupture of living tissues and may have important implications for many other biological processes, such as wound healing and tissue morphogenesis.

MicroRNA roles in the NF- κB signaling pathway during viral infections.

NF- κ B signaling network is a crucial component of innate immunity. miRNAs are a subtype of small noncoding RNAs, involved in regulation of gene expression at the posttranscriptional level. Increasing evidence has emerged that miRNAs play an important role in regulation of NF- κ B signaling pathway during viral infections. Both host and viral miRNAs are attributed to modulation of NF- κ B activity, thus affecting viral infection and clearance. Understandings of the mechanisms of these miRNAs will open a direction for development of novel antivirus drugs.

[Construction, expression and immunogenicity of eukaryotic vectors based on goat pox virus P32 gene].

The full-length P32 gene and the truncated P32 gene (MP-32) were amplified from the recombinant plasmid pMD-P32 by polymerase chain reaction (PCR) and cloned into pcDNA3. 1(+) and pcDNA3.1-CpG respectively. The recombinant plasmids (pcDNA3.1-P32, pcDNA3.1-CpG-P32 and pcDNA3. 1-CpG-MP32) were transfected into BHK-21 cells by using lipofectin. The expressed P32 protein was confirmed by indirect immunofluorescence assay (IFA). The BALB/c mice were immunized with these recombinant plasmids by intramuscular injection. The specific antibodies aginst CPV were detected by ELISA kit weekly. The murine splenic T lymphocyte subgroups CD4+ and CD8+ were detected by flow cytometry. Results showed that the P32 protein was expressed successfully in vitro. After 2 weeks post im munization, the specific IgG antibodies against CPV were detected in the vaccinated mice. The percentage of CD4+ /CD8+ T cells was significantly higher than that of the control. In conclusion, these constructed eukaryotic vectors could induce humoral and celluar immune responses in mice.