Porcine deltacoronavirus nucleocapsid protein antagonizes JAK-STAT signaling pathway by targeting STAT1 through KPNA2 degradation.

Porcine deltacoronavirus (PDCoV) is an enteric pathogenic coronavirus that causes acute and severe watery diarrhea in piglets and has the ability of cross-species transmission, posing a great threat to swine production and public health. The interferon (IFN)-mediated signal transduction represents an important component of virus-host interactions and plays an essential role in regulating viral infection. Previous studies have suggested that multifunctional viral proteins encoded by coronaviruses antagonize the production of IFN via various means. However, the function of these viral proteins in regulating IFN-mediated signaling pathways is largely unknown. In this study, we demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I IFN-mediated JAK-STAT signaling pathway. We identified that PDCoV infection stimulated but delayed the production of IFN-stimulated genes (ISGs). In addition, PDCoV inhibited JAK-STAT signal transduction by targeting the nuclear translocation of STAT1 and ISGF3 formation. Further evidence showed that PDCoV N is the essential protein involved in the inhibition of type I IFN signaling by targeting STAT1 nuclear translocation via its C-terminal domain. Mechanistically, PDCoV N targets STAT1 by interacting with it and subsequently inhibiting its nuclear translocation. Furthermore, PDCoV N inhibits STAT1 nuclear translocation by specifically targeting KPNA2 degradation through the lysosomal pathway, thereby inhibiting the activation of downstream sensors in the JAK-STAT signaling pathway. Taken together, our results reveal a novel mechanism by which PDCoV N interferes with the host antiviral response.IMPORTANCEPorcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that receives increased attention and seriously threatens the pig industry and public health. Understanding the underlying mechanism of PDCoV evading the host defense during infection is essential for developing targeted drugs and effective vaccines against PDCoV. This study demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I interferon signaling by targeting STAT1, which is a crucial signal sensor in the JAK-STAT signaling pathway. Further experiments suggested that PDCoV N-mediated inhibition of the STAT1 nuclear translocation involves the degradation of KPNA2, and the lysosome plays a role in KPNA2 degradation. This study provides new insights into the regulation of PDCoV N in the JAK-STAT signaling pathway and reveals a novel mechanism by which PDCoV evades the host antiviral response. The novel findings may guide us to discover new therapeutic targets and develop live attenuated vaccines for PDCoV infection.

Inhibition of anti-viral stress granule formation by coronavirus endoribonuclease nsp15 ensures efficient virus replication.

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs exert anti-viral functions due to their involvement in protein synthesis shut off and recruitment of innate immune signaling intermediates. The largest RNA viruses, coronaviruses, impose great threat to public safety and animal health; however, the significance of SGs in coronavirus infection is largely unknown. Infectious Bronchitis Virus (IBV) is the first identified coronavirus in 1930s and has been prevalent in poultry farm for many years. In this study, we provided evidence that IBV overcomes the host antiviral response by inhibiting SGs formation via the virus-encoded endoribonuclease nsp15. By immunofluorescence analysis, we observed that IBV infection not only did not trigger SGs formation in approximately 80% of the infected cells, but also impaired the formation of SGs triggered by heat shock, sodium arsenite, or NaCl stimuli. We further demonstrated that the intrinsic endoribonuclease activity of nsp15 was responsible for the interference of SGs formation. In fact, nsp15-defective recombinant IBV (rIBV-nsp15-H238A) greatly induced the formation of SGs, along with accumulation of dsRNA and activation of PKR, whereas wild type IBV failed to do so. Consequently, infection with rIBV-nsp15-H238A strongly triggered transcription of IFN-ß which in turn greatly affected rIBV-nsp15-H238A replication. Further analysis showed that SGs function as an antiviral hub, as demonstrated by the attenuated IRF3-IFN response and increased production of IBV in SG-defective cells. Additional evidence includes the aggregation of pattern recognition receptors (PRRs) and signaling intermediates to the IBV-induced SGs. Collectively, our data demonstrate that the endoribonuclease nsp15 of IBV interferes with the formation of antiviral hub SGs by regulating the accumulation of viral dsRNA and by antagonizing the activation of PKR, eventually ensuring productive virus replication. We further demonstrated that nsp15s from PEDV, TGEV, SARS-CoV, and SARS-CoV-2 harbor the conserved function to interfere with the formation of chemically-induced SGs. Thus, we speculate that coronaviruses employ similar nsp15-mediated mechanisms to antagonize the host anti-viral SGs formation to ensure efficient virus replication.

Formation of Robust Polydimethylsiloxane Coatings on the Flexspline Material and Mechanism of the Tribological Property Improvement.

Flexspline frictional degradation causes failure of harmonic drives. This study focused on the improvement of the flexspline tribological properties. Flexspline material 40Cr was modified with a robust polydimethylsiloxane (PDMS) coating. Etched and chemically modified films were utilized to enhance the organic PDMS coating-substrate link strength. Comparing modified and unmodified 40Cr, the surface friction coefficient decreased by 82.2%. Moreover, the modified 40Cr exhibited excellent load-bearing properties. The effects of speed and lubricant-coating interaction on the tribological properties were verified. This study provides an essential theoretical basis for improving the tribological performance of harmonic drives via soft coating modification.

Association between ERCC2 rs13181 polymorphism and ovarian cancer risk: an updated meta-analysis with 4024 subjects.

BACKGROUND: Genetic variants in the excision repair cross-complimentary group 2 (ERCC2) gene may affect individual susceptibility to cancer by modulating the capability of DNA damage repair. However, the current studies concerning the association of ERCC2 rs13181 polymorphism with ovarian cancer risk provided inconsistent evidence. METHODS: This study was to quantitatively summarize the evidence from the individual studies electronically retrieved by a meta-analysis. RESULTS: Totally, nine eligible case-control studies with 1333 cases and 2691 controls were included for the concerned association. Overall, a significant association between ERCC2 gene rs13181 polymorphism and increased risk of ovarian cancer was revealed (CC+AC vs. AA: OR 1.44, 95% CI 1.11-1.86; CC vs. AA: OR 2.12, 95% CI 1.14-3.97). Similarly, in the subgroup analyses, such association was also evident in non-Caucasian population and hospital-based studies. Noteworthily, the recombined analysis with a significant decrease in between-heterogeneity represented a significant association of the variant with increased risk of ovarian cancer after excluding the individual study not in agreement with HWE. CONCLUSION: The present study suggests that the ERCC2 gene rs13181 polymorphism might be associated with increased risk of ovarian cancer.

A genome-wide association study (GWAS) of the personality constructs in CPAI-2 in Taiwanese Hakka populations.

Here in this study we adopted genome-wide association studies (GWAS) to investigate the genetic components of the personality constructs in the Chinese Personality Assessment Inventory 2 (CPAI-2) in Taiwanese Hakka populations, who are likely the descendants of a recent admixture between a group of Chinese immigrants with high emigration intention and a group of the Taiwanese aboriginal population generally without it. A total of 279 qualified participants were examined and genotyped by an Illumina array with 547,644 SNPs to perform the GWAS. Although our sample size is small and that unavoidably limits our statistical power (Type 2 error but not Type 1 error), we still found three genomic regions showing strong association with Enterprise, Diversity, and Logical vs. Affective Orientation, respectively. Multiple genes around the identified regions were reported to be nervous system related, which suggests that genetic variants underlying the certain personalities should indeed exist in the nearby areas. It is likely that the recent immigration and admixture history of the Taiwanese Hakka people created strong linkage disequilibrium between the emigration intention-related genetic variants and their neighboring genetic markers, so that we could identify them despite with only limited statistical power.

An Approach of Producing Ultra-High-Performance Concrete with High Elastic Modulus by Nano-Al2O3: A Preliminary Study.

Ultra-high-performance concrete (UHPC) has promising applications in civil engineering. However, the elastic modulus of UHPC is relatively low compared with its compressive strength, which may result in insufficient stiffness in service. This work was carried out to explore the feasibility of producing UHPC with high elastic modulus by nano-Al2O3 (NA). Based on particle densely packing theory, the initial mixture of UHPC was designed via the modified Andreasen and Andersen model. An experimental investigation was conducted to systematically examine the effects of NA on different properties of UHPC, including its fluidity, mechanical properties, durability, and microstructure. It was found that: (1) Compared with UHPC without NA, the flexural strength, compressive strength, and elastic modulus of UHPC were improved by 7.38-16.87%, 4.08-20.58%, and 2.89-14.08%, respectively, because of the incorporation of NA; (2) the addition of NA had a prohibiting impact on the threshold pore diameter and porosity of UHPC, which suggested that NA could be conducive to its pore structure; (3) the incorporation of NA led to a decline of 2.9-11.76% in the dry shrinkage of UHPC, which suggested that incorporating NA in a proper amount could reduce the risk of cracking and alleviate the dry shrinkage of UHPC; (4) the optimal amount of NA in UHPC was 1.0%, considering the effects of NA on workability, mechanical properties, microstructure, and the durability of UHPC.

Characterization of Neutralizing Monoclonal Antibodies and Identification of a Novel Conserved C-Terminal Linear Epitope on the Hemagglutinin Protein of the H9N2 Avian Influenza Virus.

The H9N2 avian influenza virus (AIV) remains a serious threat to the global poultry industry and public health. The hemagglutinin (HA) protein is an essential protective antigen of AIVs and a major target of neutralizing antibodies and vaccines. Therefore, in this study, we used rice-derived HA protein as an immunogen to generate monoclonal antibodies (mAbs) and screened them using an immunoperoxidase monolayer assay and indirect enzyme-linked immunosorbent assay. Eight mAbs reacted well with the recombinant H9N2 AIV and HA protein, four of which exhibited potent inhibitory activity against hemagglutination, while three showed remarkable neutralization capacities. Western blotting confirmed that two mAbs bound to the HA protein. Linear epitopes were identified using the mAbs; a novel linear epitope, 480HKCDDQCM487, was identified. Structural analysis revealed that the novel linear epitope is located at the C-terminus of HA2 near the disulfide bond-linked HA1 and HA2. Alignment of the amino acid sequences showed that the epitope was highly conserved among multiple H9N2 AIV strains. The results of this study provide novel insights for refining vaccine and diagnostic strategies and expand our understanding of the immune response against AIV.

Spectrum Decomposition-Based Orbital Angular Momentum Communication of Acoustic Vortex Beams Using Single-Ring Transceiver Arrays.

The orbital angular momentum (OAM)-based acoustic vortex (AV) communication has been proven to provide a topological spinning characteristics for data transmission with an improved channel capacity, exhibiting good application prospects in underwater acoustic communications. To improve the accuracy and efficiency of data communication, the spectrum decomposition of OAM modes for OAM-multiplexed AV beams is studied with a simplified structure of single-ring transceiver arrays. The principle of spectrum decomposition for the single-OAM or OAM-multiplexed AV beams is derived based on the phase-coded approach and the orthogonal property of AVs. With the single-ring arrays of 16 transducers and 16 receivers, numerical studies and experimental measurements of eight-OAM-multiplexed AV beams transmitting ASCII codes are conducted. The formation of OAM-multiplexed AV beams is demonstrated by the cross-sectional scanning measurements, and the OAM modes are decoded successfully with a 16-point circular sampling. Compared with the traditional orthogonality-based decoding algorithm, the spectrum decomposition can be realized using a rotational measurement without the multiple premeasurements of single-OAM AV beams. The favorable results demonstrate the feasibility of the spectrum decomposition-based OAM communication for AV beams using a simplified structure of single-ring transceiver arrays, which would facilitate the practical application in underwater communications.

Mechanical Properties and Environmental Evaluation of Ultra-High-Performance Concrete with Aeolian Sand.

Ultra-high-performance concrete (UHPC) has received increasing attention in recent years due to its remarkable ductility, durability, and mechanical properties. However, the manufacture of UHPC can cause serious environmental issues. This work addresses the feasibility of using aeolian sand to produce UHPC, and the mix design, environmental impact, and mechanical characterization of UHPC are investigated. We designed the mix proportions of the UHPC according to the modified Andreasen and Andersen particle packing model. We studied the workability, microstructure, porosity, mechanical performance, and environmental impact of UHPC with three different water/binder ratios. The following findings were noted: (1) the compressive strength, flexural strength, and Young's modulus of the designed UHPC samples were in the ranges of 163.9-207.0 MPa, 18.0-32.2 MPa, and 49.3-58.9 GPa, respectively; (2) the compressive strength, flexural strength, and Young's modulus of the UHPC increased with a decrease in water/binder ratio and an increase in the steel fibre content; (3) the compressive strength-Young's modulus correlation of the UHPC could be described by an exponential formula; (4) the environmental impact of UHPC can be improved by decreasing its water/binder ratio. These findings suggest that it is possible to use aeolian sand to manufacture UHPC, and this study promotes the application of aeolian sand for this purpose.

Effect of Graphene Oxide on Mechanical Properties and Durability of Ultra-High-Performance Concrete Prepared from Recycled Sand.

Ultra-high-performance concrete (UHPC) has been used as an advanced construction material in civil engineering because of its excellent mechanical properties and durability. However, with the depletion of the raw material (river sand) used for preparing UHPC, it is imperative to find a replacement material. Recycled sand is an alternative raw material for preparing UHPC, but it degrades the performance. In this study, we investigated the use of graphene oxide (GO) as an additive for enhancing the properties of UHPC prepared from recycled sand. The primary objective was to investigate the effects of GO on the mechanical properties and durability of the UHPC at different concentrations. Additionally, the impact of the GO additive on the microstructure of the UHPC prepared from recycled sand was analysed at different mixing concentrations. The addition of GO resulted in the following: (1) The porosity of the UHPC prepared from recycled sand was reduced by 4.45-11.35%; (2) the compressive strength, flexural strength, splitting tensile strength, and elastic modulus of the UHPC prepared from recycled sand were enhanced by 8.24-16.83%, 11.26-26.62%, 15.63-29.54%, and 5.84-12.25%, respectively; (3) the resistance of the UHPC to penetration of chloride ions increased, and the freeze-thaw resistance improved; (4) the optimum mixing concentration of GO in the UHPC was determined to be 0.05 wt.%, according to a comprehensive analysis of its effects on the microstructure, mechanical properties, and durability of the UHPC. The findings of this study provide important guidance for the utilisation of recycled sand resources.

Using Graphene Sulfonate Nanosheets to Improve the Properties of Siliceous Sacrificial Materials: An Experimental and Molecular Dynamics Study.

The fabrication of high-performance cement-based materials has benefited greatly from the extensive use of graphene and its derivatives. This paper studies the effects of graphene sulfonate nanosheets (GSNSs) on sacrificial cement paste and mortar (the tested materials) and other siliceous sacrificial materials, especially their ablation behaviors and mechanical properties. Decomposition temperatures and differential scanning calorimetry were used to examine how different contents of GSNSs determines the corresponding decomposition enthalpy of the tested materials and their ablation behaviors. Molecular dynamics was also used to clarify the mechanism how the GSNSs work in the CSH (calcium silicate hydrated)/GSNSs composite to increase the resistance to high temperature. The experimental results show that: (1) the contents of GSNSs at 0.03 wt.%, 0.1 wt.%, and 0.3 wt.% brought an increase of 10.97%, 22.21%, and 17.56%, respectively, in the flexural strength of siliceous sacrificial mortar, and an increase of 1.92%, 9.16%, and 6.70% in its compressive strength; (2) the porosity of siliceous sacrificial mortar was decreased by 5.04%, 9.91%, and 7.13%, respectively, and the threshold pore diameter of siliceous sacrificial mortar was decreased by 13.06%, 35.39%, and 24.02%, when the contents of GSNSs were 0.03 wt.%, 0.1 wt.%, and 0.3 wt.%, respectively; (3) a decline of 11.16%, 28.50%, and 61.01% was found in the ablation velocity of siliceous sacrificial mortar, when the contents of GSNSs were 0.03 wt.%, 0.1 wt.%, and 0.3 wt.%, respectively; (4) when considering the ablation velocities and mechanical properties of siliceous sacrificial materials, 0.1 wt.% GSNSs was considered to be the optimal amount; (5) the GSNSs contribute to the reinforced effect of GSNSs on CSH gel through the grab of dissociated calcium and water molecules, and the chemical reaction with silicate tetrahedron to produce S-O-Si bonds. These results are expected to promoting the development of new kinds of siliceous sacrificial materials that contain GSNSs.

Effect of Inhibitor on Adsorption Behavior and Mechanism of Micro-Zone Corrosion on Carbon Steel.

A new type of inhibitor is studied in this paper. Inhibition efficiency and adsorption behavior of an inhibitor film on the steel surface is tested via the electrochemical method and theoretical calculation to establish the adsorption model. Test results confirm that inhibition efficiency is improved with the addition of an inhibitor, and the inhibitor film is formed firmly by comparing the characteristic peaks of S and N. Moreover, the micro-zone corrosion progress of Fe in 3.5% invasive NaCl-simulated seawater environment is studied. The results further show that corrosion is initiated under the zone without the inhibitor film, while it is prevented under the protection of the film. By the experiments, it is shown that inhibitor can be adsorbed on the surface of steel stably and has excellent protection performance for reinforced rebar, which can be widely used in concrete structure.

Feasibility of manufacturing ultra-high performance cement-based composites (UHPCCs) with recycled sand: A preliminary study.

Due to the excellent mechanical and durability properties, ultra-high performance cement-based composites (UHPCCs) have attracted a lot of attention during the past decades. It is noted that most existing UHPCCs are manufactured from raw materials with high quality, for instance, well-graded river sands. However, the huge consumption of river sands as construction materials has inevitably resulted in some serious ecological impacts, as reported around the world. In this regard, it shall be much beneficial if some substitutes, such as recycled sands produced through processing of construction and demolition waste (CDW), could be used to replace natural sands to manufacture the qualified UHPCCs. This paper presents such a preliminary study on the feasibility of manufacturing UHPCCs with recycled sands. A total of five UHPCCs are designed and cast with different replacement percentages of recycled sand, i.e., 0%, 30% 50%, 70% and 100% (in mass). The associated packing density of the mixed sands is estimated based on the linear packing model. The fresh and hardened properties of the UHPCCs, including the workability, strength and shrinkage, are experimentally examined. The test results indicate that it is possible to use recycled sand to replace natural river sand in the manufacture of UHPCCs; however, the amount of the recycled sand needs to be limited. In the case when the replacement percentage of the recycled sand is lower than 50% (in mass), the properties of the UHPCCs with the recycled sand are comparable with those containing river sand only.

Galvanic corrosion of duplex corrosion-resistant steel rebars under carbonated concrete conditions.

Galvanic corrosion between two different kinds of steel rebars is usually the case in practical engineering. Open circuit potential (OCP), linear polarization resistance (LPR), Tafel polarization, scanning vibrating electrode technique (SVET), scanning electron microscopy (SEM) and reflection digital holographic microscopy (DHM) were used to study the galvanic corrosion of a novel corrosion-resistant steel bar (CR) and low-carbon steel bar (LC) in simulated concrete pore solutions with different pH values and a chloride ion concentration of 5 mol L-1. The pH of the simulated concrete pore solution had a significant impact on the corrosion behaviour of CR and LC when they were in contact and were attacked by chloride ions. As the pH increased, the potential between CR and LC decreased and the driving force for the galvanic corrosion decreased. When the pH was 9.0, galvanic corrosion occurred on CR and LC at a high rate. CR developed local pitting corrosion, while LC mainly developed uniform corrosion, each with an apparent accumulation of corrosion products on the sample's surfaces. When the pH was 11.3, galvanic corrosion occurred when CR and LC were in contact. CR showed a relatively smooth surface, with only a small amount of pitting corrosion. In contrast, LC developed both pitting corrosion and uniform corrosion, and both apparent pitting corrosion and an accumulation of corrosion products on the sample surface were observed. When the pH was 13.6, there was no galvanic corrosion when CR and LC were in contact; the corrosion of CR and LC was mainly pitting corrosion. Therefore, for regions with chloride ion corrosion and severe carbonization, the galvanic corrosion between CR and LC cannot be ignored.

The Subthalamic Neurons are Activated by Both Orexin-A and Orexin-B.

The subthalamic nucleus is an important nucleus in the indirect pathway of the basal ganglia circuit and therefore is involved in motor control under both normal and pathological conditions. Morphological studies reveal that the subthalamic nucleus receives relatively dense orexinergic projections originating from the hypothalamus. Both orexin-1 (OX1) and orexin-2 (OX2) receptors are expressed in the subthalamic nucleus. To explore the functions of orexinergic system in the subthalamic nucleus, extracellular electrophysiological recordings and behavioral tests were performed in the present study. Exogenous application of orexin-A significantly increased the spontaneous firing rate from 5.70 ±â€¯0.66 Hz to 9.87 ±â€¯1.18 Hz in 64.00% subthalamic neurons recorded. OX1 receptors are involved in orexin-A-induced excitation. Application of orexin-B increased the firing rate from 7.47 ±â€¯0.92 Hz to 11.85 ±â€¯1.39 Hz in 80.95% subthalamic neurons recorded, entirely through OX2 receptors. Both OX1 and OX2 receptor antagonists decreased the firing rate in 43.75% and 62.50% subthalamic neurons recorded respectively, suggesting the involvement of endogenous orexinergic system in the control of spontaneous firing activity. Further elevated body swing test revealed that microinjection of orexins and the receptor antagonists into the subthalamic nucleus induced contralateral-biased swing and ipsilateral-biased swing, respectively. Taken together, the present study suggests that orexins play important roles in the subthalamic nucleus which may provide further evidence for the involvement of subthalamic orexinergic tone in Parkinson's disease. SIGNIFICANCE: Previous morphological studies indicate that the subthalamic nucleus receives orexinergic innervation and expresses both OX1 and OX2 receptors. Using in vivo multibarrel electrophysiological recordings, the present study revealed that exogenous application of orexin-A and orexin-B increased the spontaneous firing rate of the subthalamic neurons through OX1 and OX2 receptors. Endogenous orexinergic system was involved in the control of spontaneous firing of the subthalamic neurons. Further behavioral test revealed that intrasubthalamic application of orexins and the receptor antagonists induced biased swing behavior. The present study may provide further evidence for the involvement of subthalamic orexinergic tone in Parkinson's disease.

The Passive Film Growth Mechanism of New Corrosion-Resistant Steel Rebar in Simulated Concrete Pore Solution: Nanometer Structure and Electrochemical Study.

An elaborative study was carried out on the growth mechanism and properties of the passive film for a new kind of alloyed corrosion-resistant steel (CR steel). The passive film naturally formed in simulated concrete pore solutions (pH = 13.3). The corrosion resistance was evaluated by various methods including open circuit potential (OCP), linear polarization resistance (LPR) measurements, and electrochemical impedance spectroscopy (EIS). Meanwhile, the 2205 duplex stainless steel (SS steel) was evaluated for comparison. Moreover, the passive film with CR steel was studied by means of X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Atomic Force Microscope (AFM), and the Mott­Schottky approach. The results showed that the excellent passivity of CR steel could be detected in a high alkaline environment. The grain boundaries between the fine passive film particles lead to increasing Cr oxide content in the later passivation stage. The filling of cation vacancies in the later passivation stage as well as the orderly crystalized inner layer contributed to the excellent corrosion resistance of CR steel. A passive film growth model for CR steel was proposed.

Pitting Corrosion Behaviour of New Corrosion-Resistant Reinforcement Bars in Chloride-Containing Concrete Pore Solution.

In this study, the pitting behaviour of a new corrosion-resistant alloy steel (CR) is compared to that of low-carbon steel (LC) in a simulated concrete pore solution with a chloride concentration of 5 mol/L. The electrochemical behaviour of the bars was characterised using linear polarisation resistance (LPR) and electrochemical impedance spectroscopy (EIS). The pitting profiles were detected by reflective digital holographic microscopy (DHM), scanning electron microscopy (SEM), and the chemical components produced in the pitting process were analysed by X-ray energy dispersive spectroscopy (EDS). The results show that the CR bars have a higher resistance to pitting corrosion than the LC bars. This is primarily because of the periodic occurrence of metastable pitting during pitting development. Compared to the pitting process in the LC bars, the pitting depth grows slowly in the CR bars, which greatly reduces the risk of pitting. The possible reason for this result is that the capability of the CR bars to heal the passivation film helps to restore the metastable pits to the passivation state.