c Noroviruses (NoVs) are a leading cause of epidemic and sporadic cases of acute gastroenteritis worldwide. Oysters are well recognized as the main vectors of environmentally transmitted NoVs, and disease outbreaks linked to oyster consumption have been commonly observed. Here, to quantify the genetic diversity, temporal distribution, and circulation of oyster-related NoVs on a global scale, 1,077 oyster-related NoV sequences deposited from 1983 to 2014 were downloaded from both NCBI GenBank and the NoroNet outbreak database and were then screened for quality control. A total of 665 sequences with reliable information were obtained and were subsequently subjected to genotyping and phylogenetic analyses. The results indicated that the majority of oyster-related NoV sequences were obtained from coastal countries and regions and that the numbers of sequences in these regions were unevenly distributed. Moreover, >80% of human NoV genotypes were detected in oyster samples or oysterrelated outbreaks. A higher proportion of genogroup I (GI) (34%) was observed for oyster-related sequences than for nonoyster-related outbreaks, where GII strains dominated with an overwhelming majority of >90%, indicating that the prevalences of GI and GII are different in humans and oysters. In addition, a related convergence of the circulation trend was found between oyster-related NoV sequences and human pandemic outbreaks. This suggests that oysters not only act as a vector of NoV through environmental transmission but also serve as an important reservoir of human NoVs. These results highlight the importance of oysters in the persistence and transmission of human NoVs in the environment and have important implications for the surveillance of human NoVs in oyster samples. N orovirus (NoV) is known as the leading cause of nonbacterial acute gastroenteritis in humans and can infect people of all ages across the world (1). As a member of the family Caliciviridae, NoV is a nonenveloped, positive-sense, single-stranded RNA virus with a linear genome that contains three open reading frames (ORFs) (2). The genus Norovirus currently contains at least 6 distinct genogroups (genogroup I [GI], GII, GIII, GIV, GV, and GVI), each of which has been subdivided into multiple genotypes (3, 4). GI, GII, and GIV strains have been detected in humans and are further subdivided into 9, 22, and 2 genotypes, respectively (3, 4). One important genotype, genogroup II genotype 4 (GII.4), has been recognized recently as the predominant cause of major viral gastroenteritis epidemics worldwide (5-7) and contains a number of genetic variants (4,8).Over the past 20 years, new epidemic variants of GII.4 have emerged every 2 to 3 years (9) and usually have become the dominant strains in every season (7, 10, 11). For example, the Yerseke 2006a variant emerged in 2006, disappeared in 2008, and was replaced by the Den Haag 2006b variant (see Fig. S1 in the supplemental material). The New Orleans 2009 variant was the major player in the worldwide NoV outbreaks from 2010 to ...

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The auto-fluorescent coenzymes reduced nicotinamide dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD) allow label-free detection of cellular metabolism. The optical redox ratio, which is traditionally computed as the ratio of NADH and FAD intensities, allows quantification of cell redox state. In addition to multiple formulations of the optical redox ratio from NADH and FAD intensity measurements, a fluorescence lifetime redox ratio (FLIRR) based on the fractions of protein-bound NADH and FAD was developed to overcome the limitations of experimental factors that influence fluorescence intensity measurements. In this paper, we compare fluorescence-intensity computations of the optical redox ratio with the fluorescence lifetime redox ratio for quiescent and activated T cells. Fluorescence lifetime images of NAD(P)H and FAD of T cells were acquired with a two-photon fluorescence lifetime microscope. Metabolic perturbation experiments, including inhibition of glycolysis, oxidative phosphorylation, glutaminolysis, and fatty acid synthesis revealed differences between the intensity and lifetime redox ratios. Statistical analysis reveals that the FLIRR has a lower standard deviation and skewness (two-tail T-test, P value = 0.05) than the intensity redox ratio. Correlation analysis revealed a weak relationship between FLIRR and intensity redox ratio for individual cells, with a stronger correlation identified for activated T cells (Linear regression, R-value = 0.450) than quiescent T cells (R-value = 0.172). Altogether, the results demonstrate that while both the fluorescence lifetime and intensity redox ratios resolve metabolic perturbations in T cells, the endpoints are influenced by different metabolic processes.

Our previous study had identified ciclopirox (CPX) as a promising lead compound for treatment of ischemic stroke. To find better neuroprotective agents, a series of N-hydroxypyridone derivatives based on CPX were designed, synthesized, and evaluated in this study. Among these derivatives, compound 11 exhibits significant neuroprotection against oxygen glucose deprivation and oxidative stress-induced injuries in neuronal cells. Moreover, compound 11 possesses good blood–brain barrier permeability and superior antioxidant capability. In addition, a complex of compound 11 with olamine11·Ola possesses good water solubility, negligible hERG inhibition, and superior metabolic stability. The in vivo experiment demonstrates that 11·Ola significantly reduces brain infarction and alleviates neurological deficits in middle cerebral artery occlusion rats. Hence, compound 11·Ola is identified in our research as a prospective prototype in the innovation of stroke treatment.