This study explored social factors that are associated with the US deaths caused by COVID‐19 after the declaration of economic reopening on May 1, 2020 by President Donald Trump. We seek to understand how county‐level support for Trump interacted with social distancing policies to impact COVID‐19 death rates. Overall, controlling for several potential confounders, counties with higher levels of Trump support do not necessarily experience greater mortality rates due to COVID‐19. The predicted weekly death counts per county tended to increase over time with the implementation of several key health policies. However, the difference in COVID‐19 outcomes between counties with low and high levels of Trump support grew after several weeks of the policy implementation as counties with higher levels of Trump support suffered relatively higher death rates. Counties with higher levels of Trump support exhibited lower percentages of mobile staying at home and higher percentages of people working part time or full time than otherwise comparable counties with lower levels of Trump support. The relative negative performance of Trump‐supporting counties is robust after controlling for these measures of policy compliance. Counties with high percentages of older (aged 65 and above) persons tended to have greater death rates, as did more populous counties in general. This study indicates that policymakers should consider the risks inherent in controlling public health crises due to divisions in political ideology and confirms that vulnerable communities are at particularly high risk in public health crises.

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This paper investigates the relationships between caregivers’ parenting knowledge and early childhood development, based on a survey conducted in 1715 rural households in 100 villages located in an undeveloped rural area of western China. The results find that, first, caregivers’ parenting knowledge is positively and significantly associated with children’s development outcomes, including cognitive, language, motor, and social–emotional development; second, caregivers’ parental investments significantly mediate the link between parenting knowledge and early childhood development; third, in contrast with other parental investments, play materials (in terms of variety and quantity) and play activities in the households are the strongest mediators. Our findings might be informative for policy makers to design policies targeted to foster human capital formation in rural China.

The human kynurenine 3-monooxygenase (hKMO) is a potential therapeutic target for neurodegenerative and neurologic disorders. Inhibition of KMO by Ro 61-8048, a potent, selective, and the most widely used inhibitor of KMO, was shown effective in various models of neurodegenerative or neurologic disorders. However, the molecular basis of hKMO inhibition by Ro 61-8048 is not clearly understood. Here, we report biochemistry studies on hKMO and crystal structures of an hKMO homolog, pfKMO from Pseudomonas fluorescens, in complex with the substrate l-kynurenine and Ro 61-8048. We found that the C-terminal ∼110 aa are essential for the enzymatic activity of hKMO and the homologous C-terminal region of pfKMO folds into a distinct, all-α-helical domain, which associates with the N-terminal catalytic domain to form a unique tunnel in proximity to the substrate-binding pocket. The tunnel binds the Ro 61-8048 molecule, which fills most of the tunnel, and Ro 61-8048 is hydrogen bonded with several completely conserved residues, including an essential catalytic residue. Modification of Ro 61-8048 and biochemical studies of the modified Ro 61-8048 derivatives suggested that Ro 61-8048 inhibits the enzyme in an allosteric manner by affecting the conformation of the essential catalytic residue and by blocking entry of the substrate or product release. The unique binding sites distinguish Ro 61-8048 as a noncompetitive and highly selective inhibitor from other competitive inhibitors, which should facilitate further optimization of Ro 61-8048 and the development of new inhibitory drugs to hKMO.-Gao, J., Yao, L., Xia, T., Liao, X., Zhu, D., Xiang, Y. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048.

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The 2020 California wildfire season coincided with the peak of the COVID-19 pandemic affecting many counties in California, with impacts on air quality. We quantitatively analyzed the short-term effect of air pollution on COVID-19 transmission using county-level data collected during the 2020 wildfire season. Using time-series methodology, we assessed the relationship between short-term exposure to particulate matter (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), and Air Quality Index (AQI) on confirmed cases of COVID-19 across 20 counties impacted by wildfires. Our findings indicate that PM2.5, CO, and AQI are positively associated with confirmed COVID-19 cases. This suggests that increased air pollution could worsen the situation of a health crisis such as the COVID-19 pandemic. Health policymakers should make tailored policies to cope with situations that may increase the level of air pollution, especially during a wildfire season.

Novel 2-oxo-pyrazine-3-carboxamide-yl nucleoside analogues and their epimers were designed, synthesized and evaluated for their activities against influenza A viruses H1N1 and H3N2 in Madin-Darby canine kidney cells. All the compounds showed low cytotoxicities in these anti-influenza tests. One of the epimers, 4-[(1S, 3R, 4R, 7R)-7-hydroxy-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-3-oxo-3,4-dihydropyrazine-2-carboxamide 8a, with high antiviral activities (IC50 = 7.41, 5.63 μm for H3N2 and H1N1, respectively) and remarkable low cytotoxicity (TC50 > 200 μm), has great potential for further development as a novel anti-influenza A agent. Molecular docking of compound 8a with RNA-dependent RNA polymerase was performed to understand the binding mode between these inhibitors and the active site of RdRp and to rationalize some SARs.

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