The ongoing pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), affects thousands of people every day worldwide. Hence, drugs and vaccines effective against all variants of SARS‐CoV‐2 are crucial today. Viral genome mutations exist commonly which may impact the encoded proteins, possibly resulting to varied effectivity of detection tools and disease treatment. Thus, this study surveyed the SARS‐CoV‐2 genome and proteome and evaluated its mutation characteristics. Phylogenetic analyses of SARS‐CoV‐2 genes and proteins show three major clades and one minor clade (P6810S; ORF1ab). The overall frequency and densities of mutations in the genes and proteins of SARS‐CoV‐2 were observed. Nucleocapsid exhibited the highest mutation density among the structural proteins while the spike D614G was the most common, occurring mostly in genomes outside China and United States. ORF8 protein had the highest mutation density across all geographical areas. Moreover, mutation hotspots neighboring and at the catalytic site of RNA‐dependent RNA polymerase were found that might challenge the binding and effectivity of remdesivir. Mutation coldspots may present as conserved diagnostic and therapeutic targets were found in ORF7b, ORF9b, and ORF14. These findings suggest that the virion's genotype and phenotype in a specific population should be considered in developing diagnostic tools and treatment options.

Previous studies have suggested that caffeine reduces the risk of L-DOPA-induced dyskinesia. However, caffeine is also known to promote dopamine signaling, which seemingly contradicts this observed effect. To this end, the study aimed to clarify the mechanism of caffeine neuroprotection in vivo when excess dopamine is present. Transgenic Caenorhabditis elegans (UA57) overproducing dopamine was exposed to caffeine for 7 days and monitored by observing GFP-tagged dopaminergic (DA) neurons via fluorescence microscopy. Caffeine (10 mM) prevented neuronal cell loss in 96% of DA neurons, with a mean GFP intensity that is 40% higher than control (0.1% DMSO). To confirm if cAMP plays a role in the observed neuroprotection by caffeine, cAMP levels were elevated via forskolin (10 μM), an adenylyl cyclase activator. Forskolin (10 μM) exposure did not confer neuroprotection and was similar to control (0.1% DMSO) at the 7th day, suggesting that cAMP is not the sole secondary messenger utilized. Rotigotine (160 μM), a dopamine D2-like receptor (DOP2R) agonist, was not able to confer significant neuroprotection to the nematodes. This suggests that DOP2R activation is necessary but insufficient to mimic neuroprotection by caffeine. Lastly, co-administration of caffeine (10 mM) with olanzapine (160 μM), a DOP2R antagonist, eliminated neuroprotection. This suggests that the protective effect must involve both adenosine receptor antagonism and activation of DOP2Rs. Taken together, we show that caffeine protects DA neurons from dopamine-induced neurodegeneration and acts by modulating adenosine receptor-DOP2R interactions in C. elegans.

Epithelial–mesenchymal transition (EMT) is a biological process that involves the transformation of epithelial cells into cells with a mesenchymal phenotype, enhancing their migratory and invasive capabilities. EMT is crucial in embryonic development, tissue healing, and wound repair, and aids in forming diverse cell types and structures. However, aberrant EMT is involved in pathogenic processes, including fibrosis, cancer development, and progression. Recent studies show that EMT contributes to resistance to cancer treatment, including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in non-small cell lung cancer (NSCLC). This review discusses the intricate relationship between EMT and acquired chemoresistance to EGFR-TKIs. It details evidence on how EGFR-TKIs might induce EMT and how EMT may cause EGFR-TKI resistance. Understanding these pathways is crucial for developing effective prognostic and therapeutic strategies to predict and combat acquired chemoresistance in NSCLC, advancing the field toward more targeted and personalized treatment approaches.