SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.

Nonsense mutations that lead to the insertion of a premature termination codon (PTC) in the cystic fibrosis transmembrane conductance regulator (CFTR) transcript affect 11% of patients with cystic fibrosis (CF) worldwide and are associated with severe disease phenotype. While CF rat models have contributed significantly to our understanding of CF disease pathogenesis, there are currently no rat models available for studying CF nonsense mutations. Here we created and characterized the first homozygous CF rat model that bears the CFTR G542X nonsense mutation in the endogenous locus using CRISPR/Cas9 gene editing. In addition to displaying severe CF manifestations and developmental defects such as reduced growth, abnormal tooth enamel, and intestinal obstruction, CFTR G542X knockin rats demonstrated an absence of CFTR function in tracheal and intestinal sections as assessed by nasal potential difference and transepithelial short-circuit current measurements. Reduced CFTR mRNA levels in the model further suggested sensitivity to nonsense-mediated decay, a pathway elicited by the presence of PTCs that degrades the PTC-bearing transcripts and thus further diminishes the level of CFTR protein. Although functional restoration of CFTR was observed in G542X rat tracheal epithelial cells in response to single readthrough agent therapy, therapeutic efficacy was not observed in G542X knockin ratsin vivo. The G542X rat model provides an invaluable tool for the identification andin vivovalidation of potential therapies for CFTR nonsense mutations.

Background Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles (i.e., metronidazole [MTZ] and tinidazole) are the only FDA-approved medications. Resistance to 5- nitroimidazoles has been observed in 5–10% of cases, but may be rising. MTZ was first introduced in the early 1960s to treat T. vaginalis infections, and resistance to MTZ developed rapidly within a couple of years. This observation suggests that the potential for MTZ resistance is likely encoded in the genome of T. vaginalis. We aimed to analyze gene-expression patterns of MTZ-resistant and MTZ-sensitive T. vaginalis isolates to gain insight into resistance mechanisms. Methods T. vaginalis isolates (4 MTZ-resistant [minimal lethal concentration; MLC > 50µg/ml] and 4 MTZ-sensitive [MLC < 25µg/ml]) were grown in triplicate in Diamond’s TYM medium. MTZ susceptibility testing confirmed MTZ MLCs of T. vaginalis isolates. RNA sequencing (RNAseq) and bioinformatics analyses were used to identify differentially expressed genes (DEGs) in MTZ-resistant vs. sensitive isolates. Subsequent qPCR was used to confirm and extend RNAseq data and gene targets related to 5-nitroimidazole resistance. Results RNAseq identified DEGs in MTZ-resistant vs. sensitive isolates. DEGs from MTZ-resistant isolates included those involved in metabolic pathways relevant to 5-nitroimidazole resistance such as energy production, drug activation, and oxygen-scavenging. Other DEGs included those encoding transcription factors, ribosomal proteins, and other metabolic enzymes. RT-qPCR experiments confirmed reduced expression of genes encoding ferredoxin (Fdx) and flavin reductase 1 (FR1) in MTZ-resistant T. vaginalis isolates as compared to MTZ-sensitive isolates. Conclusion In this study, we identified several DEGs in T. vaginalis isolates resistant to MTZ. Further studies with large number of isolates representing a broad range of MTZ-susceptibility patterns are needed to identify genes that may represent new targets for future drug development.

Background The words "nutrition" and "pharmaceutical" are combined to form the phrase "nutraceutical." Nutraceuticals are foods or dietary components that have an important role in regulating and sustaining normal physiological function in humans. For the treatment of dysmenorrhoea, a variety of pharmacological medications are available, however, they all have significant side effects. Dietary supplements and lifestyle management, on the other hand, were found to have a major influence on the occurrence and control of dysmenorrhea. Objective The objective of this paper is to study a comprehensive review of the dietary and nutritional supplements with special emphasis on dysmenorrhea. This paper focuses on understanding and interpreting the details of menstrual pain and its effective nutritional diet that can be used as a treatment for avoiding menstrual discomfort. Methods The selection of data has been done by studying a combination of various research and review papers from different databases like PubMed, NCBI, Science Direct, WHO, Cochrane Library, and Web of Science from the year 2000-2022. Results Based on various papers and literature reviews, we have concluded about various dietary supplements and herbs that can be used to avoid pain during mensuration followed by its all-daily requirement of nutrition on different age groups and efficacy of treatments. Conclusion According to current evidence, young women should be instructed in the proper use of dietary supplements, nutrition, and vitamins, as well as the inclusion of effective diet and lifestyle changes such as exercise and a well-balanced diet with adequate nutrition, as these are likely to reduce the negative effects of dysmenorrhea.