A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein

Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 decades, which highlights the pressing need for antiviral therapeutics. In a high-throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV-infected cultures with 2 MBDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs, and attenuated virus infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever

Association between platelet distribution width and serum uric acid in Chinese population

© 2019 International Union of Biochemistry and Molecular Biology Platelet distribution width (PDW) is a simple and inexpensive parameter, which could predict activation of coagulation efficiently. And it has been confirmed to have a significant role in many diseases. We aimed to explore the association between PDW and hyperuricemia in a large Chinese cohort. This cross-sectional study recruited 61,091 ostensible healthy participants (29,259 males and 31,832 females) after implementing exclusion criteria. Clinical data of the enrolled population included anthropometric measurements and serum parameters. Database was sorted by gender, and the association between PDW and hyperuricemia was analyzed after dividing PDW into quartiles. Crude and adjusted odds ratios of PDW for hyperuricemia with 95% confidence intervals were analyzed using binary logistic regression models. We found no significant difference in PDW values between the genders. Males showed significantly higher incidence of hyperuricemia than females. From binary logistic regression models, significant hyperuricemia risks only were demonstrated in PDW quartiles 2 and 3 in males (P < 0.05). This study displayed close association between PDW and hyperuricemia as a risk factor. It is meaningful to use PDW as a clinical risk predictor for hyperuricemia in males. © 2019 BioFactors, 45(3):326–334, 2019

Association between screen time and suspected developmental coordination disorder in preschoolers: A national population-based study in China

IntroductionExcessive screen exposure (ESE) is a growing global public health concern. This study aims to investigate the potential association between ESE and suspected developmental coordination disorder (DCD) in Chinese pre-schoolers, with or without siblings.MethodA retrospective cohort study was conducted, involving 126,433 children from 551 cities in China. The Little Developmental Coordination Disorder Questionnaire (LDCDQ) was employed to evaluate motor impairment in children, while parents provided information on their children’s screen time in the past year. A mixed and multi-level logistic regression model was used to analyze the associations of all screen exposure measurements from the past year with LDCDQ scores and the risk of suspected DCD.ResultsThe prevalence of excessive screen exposure was 67.6% (&gt;1 h per day) and 28.9% (&gt;2 h per day) in Chinese pre-schoolers. One hour’s increase in weekday daily screen time, weekend daily screen time, and screen time before sleep in the past year was associated with a decreased total score of the LDCDQ (β were −0.690, −0.398, and −1.587, p &lt; 0.001) and an increased risk of suspected DCD by 15.3%, 9.1%, and 46.8% when adjusting for the child, family and maternal health characteristics. Excessive screen exposure decreased the total LDCDQ scores by 1.335 (&gt;1 vs. ≤1 h) and 1.162 (&gt;2 vs. ≤2 h) and increased risks of suspected DCD by 44.0% (&gt;1 vs. ≤1 h) and 31.1% (&gt;2 vs. ≤2 h) with statistical significance (each p &lt; 0.05). The stratified analysis showed that the association between screen time and LDCDQ score was stronger in children without siblings than in those with siblings.ConclusionThe risk of suspected DCD was highest for screen time exposure before bed compared with average weekday and weekend exposures. Parents should be advised to prevent their children from using electronic screens unsupervised, especially in one-child families

Aerosol Jet Printing of Graphene and Carbon Nanotube Patterns on Realistically Rugged Substrates

Direct-write additive manufacturing of graphene and carbon nanotube (CNT) patterns by aerosol jet printing (AJP) is promising for the creation of thermal and electrical interconnects in (opto)electronics. In realistic application scenarios, this however often requires deposition of graphene and CNT patterns on rugged substrates such as, for example, roughly machined and surface oxidized metal block heat sinks. Most AJP of graphene/CNT patterns has thus far however concentrated on flat wafer-or foil type substrates. Here, we demonstrate AJP of graphene and single walled CNT (SWCNT) patterns on realistically rugged plasma electrolytic-oxidized (PEO) Al blocks, which are promising heat sink materials. We show that AJP on the rugged substrates offers line resolution of down to similar to 40 mu m width for single AJP passes, however, at the cost of noncomplete substrate coverage including noncovered mu m-sized pores in the PEO Al blocks. With multiple AJP passes, full coverage including coverage of the pores is, however, readily achieved. Comparing archetypical aqueous and organic graphene and SWCNT inks, we show that the choice of the ink system drastically influences the nanocarbon AJP parameter window, deposit microstructure including crystalline quality, compactness of deposit, and inter/intrapass layer adhesion for multiple passes. Simple electrical characterization indicates aqueous graphene inks as the most promising choice for AJP-deposited electrical interconnect applications. Our parameter space screening thereby forms a framework for rational process development for graphene and SWCNT AJP on application-relevant, rugged substrates

Persistence of SARS-CoV-2 virus RNA in feces: A case series of children

AIMS To determine how long SARS-CoV-2 virus RNA persists in fecal specimens in children with COVID-19. METHODS Retrospectively, ten children with confirmed COVID-19 in the Jinan Infectious Disease Hospital Affiliated to Shandong University were enrolled between January 23, 2020 to March 9, 2020. Epidemiological, clinical, laboratory, and radiological characteristics of the children were analyzed. RT-PCR assays were performed to detect the SARS-CoV-2 virus RNA in the respiratory tract and fecal specimens in the follow-up after discharge. RESULTS Among ten patients, five (50%) were asymptomatic and five (50%) showed mild symptoms of respiratory illness. The average age of asymptomatic children was younger than that of symptomatic children (p = 0.03). The decreases in white blood cell (WBC) (p = 0.03) and lymphocyte (p = 0.03) counts were more severe in symptomatic patients than those in asymptomatic patients. During the follow-up examination after discharge, seven out of ten patients contained SARS-CoV-2 virus RNA in their fecal specimens, despite all patients showed negative results in respiratory tract specimens. One out of those seven patients relapsed. The median time from onset to being negative results in respiratory tract and fecal specimens was 9 days and 34.43 days, respectively. CONCLUSIONS SARS-CoV-2 virus RNA persists much longer in the gastrointestinal (GI) tract than that in respiratory tract

Allocation pattern and accumulation potential of carbon stock in natural spruce forests in northwest China

Background: The spruce forests are dominant communities in northwest China, and play a key role in national carbon budgets. However, the patterns of carbon stock distribution and accumulation potential across stand ages are poorly documented. Methods: We investigated the carbon stocks in biomass and soil in the natural spruce forests in the region by surveys on 39 plots. Biomass of tree components were estimated using allometric equations previously established based on tree height and diameter at breast height, while biomass in understory (shrub and herb) and forest floor were determined by total harvesting method. Fine root biomass was estimated by soil coring technique. Carbon stocks in various biomass components and soil (0&ndash;100 cm) were estimated by analyzing the carbon content of each component. Results: The results showed that carbon stock in these forest ecosystems can be as high as 510.1 t ha-1, with an average of 449.4 t ha-1. Carbon stock ranged from 28.1 to 93.9 t ha-1 and from 0.6 to 8.7 t ha-1 with stand ages in trees and deadwoods, respectively. The proportion of shrubs, herbs, fine roots, litter and deadwoods ranged from 0.1% to 1% of the total ecosystem carbon, and was age-independent. Fine roots and deadwood which contribute to about 2% of the biomass carbon should be attached considerable weight in the investigation of natural forests. Soil carbon stock did not show a changing trend with stand age, ranging from 254.2 to 420.0 t ha-1 with an average of 358.7 t ha-1. The average value of carbon sequestration potential for these forests was estimated as 29.4 t ha-1, with the lower aged ones being the dominant contributor. The maximum carbon sequestration rate was 2.47 t ha-1 year-1 appearing in the growth stage of 37&ndash;56 years. Conclusion: The carbon stock in biomass was the major contributor to the increment of carbon stock in ecosystems. Stand age is not a good predictor of soil carbon stocks and accurate evaluation of the soil carbon dynamics thus requireslong-term monitoring in situ. The results not only revealed carbon stock status and dynamics in these natural forests but were helpful to understand the role of Natural Forest Protection project in forest carbon sequestration as well.</div

Effects of heat input on microstructure evolution, mechanical and corrosion properties of TC4 alloy by keyhole TIG welding

In this study, Keyhole tungsten inert gas (TIG) process, a new variation of traditional TIG process, was performed to weld TC4 titanium alloy with a thickness of 6 mm. The effect of heat input on microstructure and their correlation with mechanical properties and corrosion behavior was studied. The results showed that the microstructure of fusion zone and heat-affected zone changed obviously due to the change of heat input. The microstructure in the joints was transformed from equiaxed primary α and α+β lamellae to complete primary β grains, and then α′ phases were precipitated in the primary β grain. With the increase of heat input, the content and length of the acicular α′ phase grains were increased, resulting in a decrease in the number of high angel grain boundaries (HAGBs). Due to the phase strengthening effect of α′ phases, the microhardness of the joints increased, and the tensile strength increased, reaching a maximum value of 1030.1 MPa when the heat input was 1118 J/mm. The impact toughness of the joints increased firstly and then decreased. The corrosion behavior of the joints was worse than that of the base metal (BM). The best corrosion resistance was obtained when the heat input was 1046 J/mm. It concluded that the excellent comprehensive properties can be obtained when the heat input was in the range of 1046–1118 J/mm