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Vaccinia virus (VACV) is a member of the Poxviridae family and served as the vaccine strain used to eradicate smallpox. As a large double-stranded DNA virus, VACV exhibits a broad host range and remains a model organism for studying viral evolution and gene expression. Codon usage bias (CUB) is a fundamental feature of genome evolution that reflects the interplay between mutational pressure and natural selection. In this study, we systematically analyzed codon usage patterns in 107 strains of Vaccinia virus (VACV) to uncover the driving forces behind its genomic evolution and host adaptation. Our findings revealed a strong A/T bias across all codon positions, particularly at the third codon position (AT3 = 66.59
In this study, high-throughput proteomics and bioinformatics techniques were employed to analyse protein expression in adult Musca domestica, a holometabolous insect. A total of 391 peptides were identified in a susceptible strain of M. domestica adults, corresponding to 138 protein groups with diverse molecular weights (9.70–357.90 kDa), isoelectric points (4.48–9.48) and amino acids (82-3173). Based on gene ontology annotation, the expressed proteins were mainly associated with gluconeogenesis (37.50
In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-breaking antioxidant H-290/51 (Astra-Zeneca, Mölndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4, 21, or 34 °C for 3 h resulted in breakdown of the blood-brain barrier (BBB), brain edema, and neuronal injuries, which all differed in severity depending upon ambient temperatures. The changes were moderate at 21 °C, 120-180 % larger at 34 °C, and almost absent at 4 °C. In rats chronically treated with NPs (SiO2, Cu, or Ag; 50-60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a two- to fourfold increase at 21 °C, a four- to sixfold increase at 34 °C, and three- to fourfold increase at 4 °C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperatures followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o., 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21 and 34 °C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (-30 min, 0 min, and +30 min). These observations are the first to show that NPs exacerbate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.
There is an unmet need for developing drugs for the treatment of gonorrhea due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug-resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On 23 April 2021, the US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institute of Allergy and Infectious Diseases of the National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of that workshop.
Bacterial topoisomerases are enzymes critical for maintaining genomic DNA integrity and ensuring bacterial cell survival, making them ideal targets for antibacterial agents. Bacterial topoisomerase inhibitors, such as quinolones and fluoroquinolones, target two enzymes, DNA gyrase and topoisomerase IV, and inhibit the control of DNA supercoiling/decatenation, leading to impaired DNA replication and bacterial cell death. Since their initial discovery, many quinolones and fluoroquinolones have been developed with activity against a wide range of bacterial species, contributing significantly to the treatment of various infectious diseases worldwide. Fluoroquinolones such as levofloxacin and ciprofloxacin remain important and effective therapeutic options today due to their broad-spectrum antibacterial activity, chemical stability and high bioavailability. However, side effects of fluoroquinolones have become a concern, leading to warnings being issued in the United States, Europe and the United Kingdom. Furthermore, in many countries, the prevalence of fluoroquinolone-resistant bacteria has been steadily increasing each year, which poses a serious threat to public health. The clinical development of new non-quinolone bacterial topoisomerase inhibitors (for example, zoliflodacin, gepotidacin and fobrepodacin) offers a promising solution to these issues and has the potential to play a crucial role in combating the growing problem of antimicrobial resistance. This review article will discuss the evolution of quinolone and fluoroquinolone antibacterial agents as key topoisomerase inhibitors, examine their current clinical applications and challenges to future development, and explore the potential of new topoisomerase inhibitors.
