Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences.

External guide sequence (EGS) RNAs are associated with ribonuclease P (RNase P), a tRNA processing enzyme, and represent promising agents for gene-targeting applications as they can direct RNase-P-mediated cleavage of a target mRNA. Using murine cytomegalovirus (MCMV) as a model system, we examined the antiviral effects of an EGS variant, which was engineered using in vitro selection procedures. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin. In vitro, the EGS variant was 60 times more active in directing RNase P cleavage of the target mRNA than the EGS originating from a natural tRNA. In MCMV-infected cells, the variant reduced mCSP expression by 92% and inhibited viral growth by 8,000-fold. In MCMV-infected mice hydrodynamically transfected with EGS-expressing constructs, the EGS variant was more effective in reducing mCSP expression, decreasing viral production, and enhancing animal survival than the EGS originating from a natural tRNA. These results provide direct evidence that engineered EGS variants with higher targeting activity in vitro are also more effective in reducing gene expression in animals. Furthermore, our findings imply the possibility of engineering potent EGS variants for therapy of viral infections

Phylogenetic Implication of Large Intergenic Spacers: Insights from a Mitogenomic Comparison of Prosopocoilus Stag Beetles (Coleoptera: Lucanidae)

To explore the characteristics of mitogenomes and discuss the phylogenetic relationships within the genus Prosopocoilus, the mitogenomes of two species (P. castaneus and P. laterotarsus) were newly sequenced and comparatively analyzed. The arrangement of the mitogenome in these two lucanid beetles was the same as that in the inferred ancestral insect, and the nucleotide composition was highly biased towards A + T as in other lucanids. The evolutionary rates of 13 protein-coding genes (PCGs) suggested that their evolution was based on purifying selection. Notably, we found evidence of the presence of a large IGS between trnI and trnQ genes, whose length varied from 375 bp (in P. castaneus) to 158 bp (in P. laterotarsus). Within the large IGS region, a short sequence (TAAAA) was found to be unique among these two species, providing insights into phylogenomic reconstruction. Phylogenetic analyses were performed using the maximum likelihood (IQ-TREE) and Bayesian (PhyloBayes) methods based on 13 protein-coding genes (PCGs) in nucleotides and amino acids (AA) from published mitogenomes (n = 29). The genus Prosopocoilus was found to constitute a distinct clade with high nodal support. Overall, our findings suggested that analysis of the characteristics of the large IGS (presence or absence, size, and location) in mitogenomes of the genus Prosopocoilus may be informative for the phylogenetic and taxonomic analyses and for evaluation of the genus Prosopocoilus, despite the dense sampling materials needed

Association between systemic immunity-inflammation index and hypertension in US adults from NHANES 1999–2018

Abstract Hypertension is a disease closely related to inflammation, and the systemic immunity-inflammation index (SII) is a new and easily detectable inflammatory marker. We aimed to investigate the association between SII and hypertension risk in a adult population in the US. We utilized data from the National Health and Nutrition Examination Survey spanning from 1999 to 2018, incorporating comprehensive information from adults reporting hypertension. This included details on blood pressure monitoring, complete blood cell counts, and standard biochemical results. The SII was computed as the platelet count multiplied by the neutrophil count divided by the lymphocyte count. We employed a weighted multivariate logistic regression model to examine the correlation between SII and hypertension. Subgroup analyses were conducted to explore potential influencing factors. Furthermore, smooth curve fitting and two-piecewise logistic regression analysis were employed to describe non-linear relationships and identify inflection points. This population-based study involved 44,070 adults aged 20–85 years. Following Ln-transformation of the SII, multivariable logistic regression revealed that, in a fully adjusted model, participants in the highest quartile of Ln(SII) had a 12% increased risk of hypertension compared to those in the lowest quartile, which was statistically significant (OR:1.12; 95% CI 1.01, 1.24; P  0.05). Additionally, the association between Ln(SII) and hypertension displayed a U-shaped curve, with an inflection point at 5.89 (1000 cells/μl). Based on this research result, we found a U-shaped correlation between elevated SII levels and hypertension risk in American adults, with a inflection point of 5.89 (1000 cells)/μl). To validate these findings, larger scale prospective surveys are needed to support the results of this study and investigate potential mechanisms

Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences.

External guide sequence (EGS) RNAs are associated with ribonuclease P (RNase P), a tRNA processing enzyme, and represent promising agents for gene-targeting applications as they can direct RNase-P-mediated cleavage of a target mRNA. Using murine cytomegalovirus (MCMV) as a model system, we examined the antiviral effects of an EGS variant, which was engineered using in vitro selection procedures. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin. In vitro, the EGS variant was 60 times more active in directing RNase P cleavage of the target mRNA than the EGS originating from a natural tRNA. In MCMV-infected cells, the variant reduced mCSP expression by 92% and inhibited viral growth by 8,000-fold. In MCMV-infected mice hydrodynamically transfected with EGS-expressing constructs, the EGS variant was more effective in reducing mCSP expression, decreasing viral production, and enhancing animal survival than the EGS originating from a natural tRNA. These results provide direct evidence that engineered EGS variants with higher targeting activity in vitro are also more effective in reducing gene expression in animals. Furthermore, our findings imply the possibility of engineering potent EGS variants for therapy of viral infections

Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences

External guide sequence (EGS) RNAs are associated with ribonuclease P (RNase P), a tRNA processing enzyme, and represent promising agents for gene-targeting applications as they can direct RNase-P-mediated cleavage of a target mRNA. Using murine cytomegalovirus (MCMV) as a model system, we examined the antiviral effects of an EGS variant, which was engineered using in vitro selection procedures. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin. In vitro, the EGS variant was 60 times more active in directing RNase P cleavage of the target mRNA than the EGS originating from a natural tRNA. In MCMV-infected cells, the variant reduced mCSP expression by 92% and inhibited viral growth by 8,000-fold. In MCMV-infected mice hydrodynamically transfected with EGS-expressing constructs, the EGS variant was more effective in reducing mCSP expression, decreasing viral production, and enhancing animal survival than the EGS originating from a natural tRNA. These results provide direct evidence that engineered EGS variants with higher targeting activity in vitro are also more effective in reducing gene expression in animals. Furthermore, our findings imply the possibility of engineering potent EGS variants for therapy of viral infections

Photocatalytic Degradation of Rhodamine B on Anatase, Rutile, and Brookite TiO2

This study compared the photocatalytic activities for the degradation of Rhodamine B (RhB) in aqueous solutions of anatase, rutile, and brookite TiO2. The TiO2 powders were prepared at low temperature. As compared with rutile obtained by a conventional high temperature calcination, the ruffle TiO2 prepared by the low temperature route had a smaller particle size, higher surface area, and more surface hydroxyl groups, and it gave a high photocatalytic activity. Rutile gave a faster photocatalysis reaction rate than anatase TiO2 for the same particle size and surface area. A pure brookite phase showed a lower photocatalytic activity when this was expressed in moles converted RhB per hour than the anatase and rutile phases. However, its areal photocatalytic activity expressed in moles converted RhB per hour per surface area was much higher than that of anatase and rutile TiO2