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Severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne bunyavirus, causes an emerging viral hemorrhagic fever with a high mortality rate. SFTSV nonstructural protein S (NSs) is a virulence factor that sequesters antiviral proteins into autophagic vesicles for degradation to escape host immune response. SAFA (Nuclear scaffold attachment factor A), an RNA sensor, recognizes viral RNA and is retained in the cytoplasm upon RNA virus SFTSV infection and then activates innate immunity. It is unclear whether NSs mediates the escape of SAFA-mediated antiviral response. Here we showed that SFTSV NSs can inhibit SAFA-dependent antiviral response via autophagy. We used SAFA-NLS (the nuclear localization signal) mutant to transfect SAFA knocked-out MEF cells and found that the cytoplasmic SAFA promoted innate immune response to poly(I:C) stimulating. Importantly, NSs interacted with the AAA+ domain of SAFA and retained SAFA in the cytoplasm thereby suppressing SAFA-mediated antiviral response. Mechanistically, SFTSV NSs degraded cytoplasmic SAFA via SQSTM1/p62-dependent autophagy and sequestered SAFA into autophagic vesicles for degradation through promoting the interaction between SAFA and LC3. In conclusion, our results indicate a novel mechanism of SFTSV NSs to escape host antiviral immune response by recruiting SAFA into autophagic flux for degradation.

Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by a tick-borne virus SFTSV with a mortality rate of up to 30%. Currently, there is no vaccine or effective therapy for SFTS. Neutralizing monoclonal antibody therapy, which provides immediate passive immunity and may limit disease progression, has emerged as a reliable approach for developing therapeutic drugs for SFTS. In this study, 4 human monoclonal antibodies (hmAbs) derived from convalescent SFTS patients’ lymphocytes based on human single-chain variable fragment antibody libraries were tested for their neutralizing activities in cells and their treatment effect in animals individually and in pair combinations. The neutralization test showed that all 4 hmAbs exhibited strong neutralizing activity against SFTSV infection in vitro . The protection rate of hmAbs 4-6, 1F6, 1B2, and 4-5 against SFTSV lethal challenge in IFNAR1 -/- A129 mice are 50%, 16.7%, 83.3%, and 66.7%, respectively. Notably, the pair combination of antibodies (1B2 and 4-5, 1B2 and 1F6) that recognized distinct epitopes protected 100% of mice against SFTSV lethal challenge. In conclusion, our findings indicate that the pair combinations of hmAbs 1B2 and 4-5 or hmAbs 1B2 and 1F6 may serve as promising therapeutic drugs for treating SFTSV infection.

We sequenced DNA from spleens of rodents captured in rural areas of Qingdao, East China, during 2013-2015. We found 1 Apodemus agrarius mouse infected with Rickettsia conorii, indicating a natural Mediterranean spotted fever foci exists in East China and that the range of R. conorii could be expanding.

Background: School-aged children were reported to act as the main transmitter during influenza epidemic seasons. It is vital to set up an early detection method to help with the vaccination program in such a high-risk population. However, most relative studies only focused on the general population. Our study aims to describe the influenza epidemiology characteristics in Hubei Province and to introduce the moving epidemic method to establish the epidemic thresholds for age-specific groups. Methods: We divided the whole population into pre-school, school-aged and adult groups. The virology data from 2010/2011 to 2017/2018 were applied to the moving epidemic method to establish the epidemic thresholds for the general population and age-specific groups for the detection of influenza in 2018/2019. The performances of the model were compared by the cross-validation process. Results: The epidemic threshold for school-aged children in the 2018/2019 season was 15.42%. The epidemic thresholds for influenza A virus subtypes H1N1 and H3N2 and influenza B were determined as 5.68%, 6.12% and 10.48%, respectively. The median start weeks of the school-aged children were similar to the general population. The cross-validation process showed that the sensitivity of the model established with school-aged children was higher than those established with the other age groups in total influenza, H1N1 and influenza B, while it was only lower than the general population group in H3N2. Conclusions: This study proved the feasibility of applying the moving epidemic method in Hubei Province. Additional influenza surveillance and vaccination strategies should be well-organized for school-aged children to reduce the disease burden of influenza in China.

The selective abnormal growth of Goss grains in magnetic sheets of Fe-3%Si （grade Hi-B） induced by second-phase particles （AlN and MnS） was studied using a modified Monte Carlo Ports model. The starting microstructures for the simulations were generated from electron backscatter diffraction （EBSD） orientation imaging maps of recrystallized samples. In the simulation, second-phase particles were assumed to be randomly distributed in the initial microstructures and the Zener drag effect of particles on Goss grain boundaries was assumed to be selectively invalid because of the unique properties of Goss grain boundaries. The simulation results suggest that normal growth of the matrix grains stagnates because of the pinning effect of particles on their boundaries. During the onset of abnormal grain growth, some Goss grains with concave boundaries in the initial microstructure grow fast abnormally and other Goss grains with convex boundaries shrink and eventually disappear.

The present work aims to investigate the effects of prior grain size of hot rolled sheets after normalization on microstructure, texture evolution, recrystallization kinetics, and magnetic properties in 1.6% Si non-oriented silicon steel. With the increase of normalizing temperature, coarse grains will be produced, which directly leads to different recrystallization behaviors. The microstructure with a smaller grain size before cold rolling has a slow driving force at the early recrystallization stage, then at the later recrystallization stage, the grains have relatively fast kinetics by annexing adjacent deformed grains. By contrast, the microstructure with a larger grain size before cold rolling has a faster dynamic force in early recrystallization, and the shear band provides nucleation location and stores energy for recrystallization, while the dynamic force in the later recrystallization is relatively slow. The magnetic induction intensity increases with the increase of grain size before cold rolling, P 1.5/50 , P 1.0/400 and P 1.0/1000 decrease first and then increase. When the grain size before cold rolling is 154.8  μ m, the grain size of the finished sheet is 112.6  μ m, the magnetic induction intensity is 1.738 T, and the optimal iron losses for P 1.5/50 , P 1.0/400 , and P 1.0/1000 were 2.311W/kg, 18.399W/kg and 78.48W/kg, respectively.

Casein kinase 2 （CK2） is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy. Because allosteric inhibitors can avoid the shortcomings of conventional kinase inhibitors, this study was aimed to discover a new allosteric site in CK2α and to investigate the effects of mutations in this site on the activity of CK2α. Using AIIosite based on protein dynamics and structural alignment, we predicted a new allosteric site that was partly located in the αC helix of CK2α. Five residues exposed on the surface of this site were mutated to validate the prediction. Kinetic analyses were performed using a luminescent ADP detection assay by varying the concentrations of a peptide substrate, and the results showed that the mutations 178C and 178W decreased CK2α activity, whereas V31R, K75E, 182C and P109C increased CK2α activity. Potential allosteric pathways were identified using the Monte Carlo path generation approach, and the results of these predicted allosteric pathways were consistent with the mutation analysis. Multiple sequence alignments of CK2a with the other kinases in the family were conducted using the ClustaIX method, which revealed the diversity of the residues in the site. In conclusion, we identified a new allosteric site in CK2α that can be altered to modulate the activity of the kinase. Because of the high diversity of the residues in the site, the site can be targeted using rational drug design of specific CK2α inhibitors for biological relevance.

The effect of smelting processes on mechanical properties and microstructure of reduced activation ferritic steels was studied.Creep properties and impact toughness of reduced activation ferritic steels were obviously improved by vacuum induction melting followed by consumable electrode remelting process in comparison with the conventional vacuum induction melting process.The difference of impact toughness and creep properties between both steels mainly depended on the aspect ratio and mean size of precipitates.Decreasing the aspect ratio of carbides makes development of a shear band more difficult , which could increase impact energy and creep resistance.

This paper summarizes the negative effects on geological environment caused by groundwater exploitation and its distribution. There are seven main types of the geological environment negative effects, which are generally as follows:(1) Constant decrease of groundwater level is mainly distributed in China(East Asia), India(South Asia), Tajikistan(Central Asia) and Saudi Arabia(West Asia);(2) land subsidence occurs mainly in eastern plains of East Asia and west Siberian Plain of North Asia;(3) seawater intrusion occurs mainly in China, Japan and South Korea in East Asia, Philippines and Indonesia in Southeast Asia, the Indian coastal areas in South Asia;(4) groundwater level decline caused by groundwater exploitation in oil fields;(5) mining collapse is mainly in 50° to 70° north latitude band;(6) the total area of karst collapse in China of East Asia is as much as 197.05 km~2; and(7) ground fracture is mainly distributed in the North China Plain, Fenwei Plain and the Yangtze River Delta. Asia can be divided into 6 zones in terms of the geological environment negative effect caused by groundwater exploitation. According to analysis, with the increasing intensity of human activities, geological environment issues become more and more serious, therefore it is vital to control the human activities within the scope of 5× 10~5 people/km~2 to 9.9× 10~5 people/km~2 for the effective control of the size of the affected area by geological environment problems.

In the shaping process of cross wedge rolling(CWR), metal undergoes a complex microstructural evolution, which affects the quality and mechanical properties of the product. Through secondary development of the DEFORM-3D software, we developed a rigid plastic finite element model for a CWR-processed rear axle tube, coupled with thermomechanical and microstructural aspects of workpieces. Using the developed model, we investigated the microstructural evolution of the CWR process. Also, the influence of numerous parameters, including the initial temperature of workpieces, the roll speed, the forming angle, and the spreading angle, on the grain size and the grain-size uniformity of the rolled workpieces was analyzed. The numerical simulation was verified through rolling and metallographic experiments. Good agreement was obtained between the calculated and experimental results, which demonstrated the reliability of the model constructed in this work.