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.

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.

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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.

Background: There is a substantial body of evidence supporting the association between maternal active smoking during pregnancy and child development, but the association between prenatal exposure to environmental tobacco smoke (ETS) and early child development has not been well documented. This cross-sectional study examines the association between prenatal exposure to ETS and the development of children in their first two years of life. Methods: We interviewed the primary caregivers of 446 children under two years old in rural Guizhou Province, China. Based on self-reported assessments about whether the mother was exposed to ETS during pregnancy, we divided the children into the ETS-exposed group or the non-exposed group. Sociodemographic information was collected through a questionnaire. The cognitive, language, motor, and socioemotional abilities of children were assessed using the Bayley Scales of Infant Development III (BSID-III). A multivariate linear regression model adjusting for confounding variables was used to estimate the association of interest. Results: About 60% of mothers experienced ETS exposure during pregnancy. Cognitive and language scores were lower among children in the ETS-exposed group. When adjusting for characteristics of the child, the mother, the household, and village fixed effects, prenatal exposure to ETS was associated with lower cognition scores (−3.41; 95% confidence interval (CI): −6.39 to −0.42; p = 0.03) and language scores (−3.01; 95% CI: −5.39 to −0.09; p = 0.04). Frequency of prenatal exposure to ETS was also negatively associated with language development (−0.48; 95% CI: −0.87 to −0.09; p = 0.02) before children reached two years old. Conclusions: Prenatal exposure to ETS is negatively associated with the cognitive and language development of rural young children within their first two years of life. The government should take action to raise public awareness about the negative effects of tobacco use, with an emphasis on the protection of pregnant women and their children, in order to carry through comprehensive smoke-free laws in rural areas, while also increasing tobacco taxation.

No abstract

The hemagglutinin (HA) glycoproteins of influenza viruses play a key role in binding host cell receptors and in mediating virus-host cell membrane fusion during virus infection. Upon virus entry, HA is triggered by low pH and undergoes large structural rearrangements from a prefusion state to a postfusion state. While structures of prefusion state and postfusion state of HA have been reported, the intermediate structures remain elusive. Here, we report two distinct low pH intermediate conformations of the influenza virus HA using cryo-electron microscopy (cryo-EM). Our results show that a decrease in pH from 7.8 to 5.2 triggers the release of fusion peptides from the binding pockets and then causes a dramatic conformational change in the central helices, in which the membrane-proximal ends of the central helices unwind to an extended form. Accompanying the conformational changes of the central helices, the stem region of the HA undergoes an anticlockwise rotation of 9.5 degrees and a shift of 15 Å. The HA head, after being stabilized by an antibody, remains unchanged compared to the neutral pH state. Thus, the conformational change of the HA stem region observed in our research is likely to be independent of the HA head. These results provide new insights into the structural transition of HA during virus entry.

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.