The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

Microloan markets allow individual borrowers to raise funding from multiple individual lenders. We use a unique panel dataset which tracks the funding dynamics of borrower listings on Prosper.com, the largest microloan market in the United States. We find evidence of rational herding among lenders. Well-funded borrower listings tend to attract more funding after we control for unobserved listing heterogeneity and payoff externalities. Moreover, instead of passively mimicking their peers (irrational herding), lenders engage in active observational learning (rational herding); they infer the creditworthiness of borrowers by observing peer lending decisions, and use publicly observable borrower characteristics to moderate their inferences.Counterintuitively, obvious defects (e.g., poor credit grades) amplify a listing's herding momentum, as lenders infer superior creditworthiness to justify the herd. Similarly, favorable borrower characteristics (e.g., friend endorsements) weaken the herding effect, as lenders attribute herding to these observable merits. Follow-up analysis shows that rational herding beats irrational herding in predicting loan performance.

SUMMARY Background Avian influenza A(H7N9) virus has caused human infections in China since 2013, and a large epidemic in 2016–17 has prompted concerns of whether the epidemiology has changed to suggest an increasing pandemic threat. Our study aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of A(H7N9) case-patients in the 2016–17 epidemic wave compared with previous waves. Methods We obtained information about all laboratory-confirmed human cases of A(H7N9) virus infection reported in mainland China as of 23 February 2017. We described the epidemiological characteristics across epidemic waves, and estimated the risk for death, mechanical ventilation, and admission to the intensive care unit for patients who required hospitalization for medical reasons. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge. Findings The 2016–17 A(H7N9) epidemic wave began earlier, spread to more counties in affected provinces and had more confirmed cases than previous epidemic waves. There was an increase in the proportion of cases in middle-aged adults and in semi-urban and rural residents. The clinical severity of hospitalized cases in 2016–17 was comparable to the previous epidemic waves. Interpretation Age distribution and case sources changed gradually across epidemic waves, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimize the risk of human infection with A(H7N9) virus. Funding The National Science Fund for Distinguished Young Scholars (grant no. 81525023).

The format of pricing contracts varies substantially across business contexts, a major variable being whether a contract imposes a fixed fee payment. This paper examines how the use of the fixed fee in pricing contracts affects market outcomes of a manufacturer-retailer channel. Standard economic theories predict that channel efficiency increases with the introduction of the fixed fee and is invariant to its framing. We conduct a laboratory experiment to test these predictions. Surprisingly, the introduction of the fixed fee fails to increase channel efficiency. Moreover, the framing of the fixed fee does make a difference: an opaque frame as quantity discounts achieves higher channel efficiency than a salient frame as a two-part tariff, although these two contractual formats are theoretically equivalent. To account for these anomalies, we generalize the standard economic model by allowing the retailer's utilities to be reference dependent so that the up-front fixed fee payment is perceived as a loss and the subsequent retail profits as a gain. We embed this reference-dependent utility function in a quantal response equilibrium framework where the retailer is allowed to make decision mistakes due to computational complexity. The key prediction of this behavioral model is that channel efficiency decreases with loss aversion for sufficiently Nash-rational retailers. Consistent with this prediction, the estimated loss-aversion coefficient is 1.37 in the two-part tariff condition, significantly higher than 1.27 in the quantity discount condition. At the same time, loss aversion dominates contract complexity in explaining the data. Lastly, we conduct a follow-up experiment to confirm the central role of loss aversion as a behavioral driver. In one condition, the retailer becomes less loss averse when we temporally compress the fixed fee payment and the realization of retail profits, which supports the loss aversion theory. In the other condition, the retailer's contract acceptance rate does not decline when we reward the manufacturer a higher cash payment for each experimental point earned, which rules out the competing hypothesis that the retailer rejects contract offers due to fairness concerns.fixed fee, two-part tariffs, quantity discounts, distribution channels, loss aversion, behavioral economics, experimental economics

Popularity information is usually thought to reinforce existing sales trends by encouraging customers to flock to mainstream products with broad appeal. We suggest a countervailing market force: popularity information may benefit niche products with narrow appeal disproportionately, because the same level of popularity implies higher quality for narrow-appeal products than for broad-appeal products. We examine this hypothesis empirically using field experiment data from a web site that lists wedding service vendors. Our findings are consistent with this hypothesis: narrow-appeal vendors receive more visits than equally popular broad-appeal vendors after the introduction of popularity information.

Strawberry (Fragaria × ananassa Duch), a fruit of economic and nutritional importance, is also a model species for fleshy fruits and genomics in Rosaceae. Strawberry fruit quality at different harvest stages is a function of the fruit's metabolite content, which results from physiological changes during fruit growth and ripening. In order to investigate strawberry fruit development, untargeted (GC-MS) and targeted (HPLC) metabolic profiling analyses were conducted. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to explore the non-polar and polar metabolite profiles from fruit samples at seven developmental stages. Different cluster patterns and a broad range of metabolites that exerted influence on cluster formation of metabolite profiles were observed. Significant changes in metabolite levels were found in both fruits turning red and fruits over-ripening in comparison with red-ripening fruits. The levels of free amino acids decreased gradually before the red-ripening stage, but increased significantly in the over-ripening stage. Metabolite correlation and network analysis revealed the interdependencies of individual metabolites and metabolic pathways. Activities of several metabolic pathways, including ester biosynthesis, the tricarboxylic acid cycle, the shikimate pathway, and amino acid metabolism, shifted during fruit growth and ripening. These results not only confirmed published metabolic data but also revealed new insights into strawberry fruit composition and metabolite changes, thus demonstrating the value of metabolomics as a functional genomics tool in characterizing the mechanism of fruit quality formation, a key developmental stage in most economically important fruit crops.

Background The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to estimate the influenza-associated excess respiratory mortality in mainland China for the 2010-11 through 2014-15 seasons. MethodsWe obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005-15. Disease surveillance points with an annual average mortality rate of less than 0•4% between 2005 and 2015 or an annual mortality rate of less than 0•3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age <60 years and ≥60 years) and aggregated by province. The overall annual population data of each province and national annual respiratory mortality data were compiled from the China Statistical Yearbook. Influenza surveillance data on weekly proportion of samples testing positive for influenza virus by type or subtype for 31 provinces were extracted from the National Sentinel Hospitalbased Influenza Surveillance Network. We estimated influenza-associated excess respiratory mortality rates between the 2010-11 and 2014-15 seasons for 22 provinces with valid data in the country using linear regression models. Extrapolation of excess respiratory mortality rates was done using random-effect meta-regression models for nine provinces without valid data for a direct estimation of the rates. Findings We fitted the linear regression model with the data from 22 of 31 provinces in mainland China, representing 83•0% of the total population. We estimated that an annual mean of 88 100 (95% CI 84 200-92 000) influenza-associated excess respiratory deaths occurred in China in the 5 years studied, corresponding to 8•2% (95% CI 7•9-8•6) of respiratory deaths. The mean excess respiratory mortality rates per 100 000 person-seasons for influenza A(H1N1)pdm09, A(H3N2), and B viruses were 1•6 (95% CI 1•5-1•7), 2•6 (2•4-2•8), and 2•3 (2•1-2•5), respectively. Estimated excess respiratory mortality rates per 100 000 person-seasons were 1•5 (95% CI 1•1-1•9) for individuals younger than 60 years and 38•5 (36•8-40•2) for individuals aged 60 years or older. Approximately 71 000 (95% CI 67 800-74 100) influenzaassociated excess respiratory deaths occurred in individuals aged 60 years or older, corresponding to 80% of such deaths. Interpretation Influenza was associated with substantial excess respiratory mortality in China between 2010-11 and 2014-15 seasons, especially in older adults aged at least 60 years. Continuous and high-quality surveillance data across China are needed to improve the estimation of the disease burden attributable to influenza and the best public health interventions...

Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2.