BackgroundThe coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. MethodsWe collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R t ) at the provincial level. FindingsWe collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33-56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4•4 days (95% CI 0•0-14•0) for the period of Dec 24 to Jan 27, to 2•6 days (0•0-9•0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5•2 days (1•8-12•4) and the mean serial interval at 5•1 days (1•3-11•6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1•08 (95% CI 0•74-1•54) in Shenzhen city of Guangdong province and 1•71 (1•32-2•17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. Interpretation Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province.
Human utilization of the mulberry–silkworm interaction started at least 5,000 years ago and greatly influenced world history through the Silk Road. Complementing the silkworm genome sequence, here we describe the genome of a mulberry species Morus notabilis. In the 330-Mb genome assembly, we identify 128 Mb of repetitive sequences and 29,338 genes, 60.8% of which are supported by transcriptome sequencing. Mulberry gene sequences appear to evolve ~3 times faster than other Rosales, perhaps facilitating the species’ spread worldwide. The mulberry tree is among a few eudicots but several Rosales that have not preserved genome duplications in more than 100 million years; however, a neopolyploid series found in the mulberry tree and several others suggest that new duplications may confer benefits. Five predicted mulberry miRNAs are found in the haemolymph and silk glands of the silkworm, suggesting interactions at molecular levels in the plant–herbivore relationship. The identification and analyses of mulberry genes involved in diversifying selection, resistance and protease inhibitor expressed in the laticifers will accelerate the improvement of mulberry plants.
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).
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...
SUMMARY Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM2 isoform, effectively constraining lower glycolysis. Here, we report the discovery of PKM2 activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM2 activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the nonessential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress.
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