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Data-driven approaches such as neural networks are increasingly used for deep excavations due to the growing amount of available monitoring data in practical projects. However, most neural network models only use the data from a single monitoring point and neglect the spatial relationships between multiple monitoring points. Besides, most models lack flexibility in providing predictions for multiple days after monitoring activity. This study proposes a sequence-to-sequence (seq2seq) two-dimensional (2D) convolutional long short-term memory neural network (S2SCL2D) for predicting the spatiotemporal wall deflections induced by deep excavations. The model utilizes the data from all monitoring points on the entire wall and extracts spatiotemporal features from data by combining the 2D convolutional layers and long short-term memory (LSTM) layers. The S2SCL2D model achieves a long-term prediction of wall deflections through a recursive seq2seq structure. The excavation depth, which has a significant impact on wall deflections, is also considered using a feature fusion method. An excavation project in Hangzhou, China, is used to illustrate the proposed model. The results demonstrate that the S2SCL2D model has superior prediction accuracy and robustness than that of the LSTM and S2SCL1D (one-dimensional) models. The prediction model demonstrates a strong generalizability when applied to an adjacent excavation. Based on the long-term prediction results, practitioners can plan and allocate resources in advance to address the potential engineering issues.

Planar sliding is one of the frequently observed types of failure in rock slopes. Kinematic analysis is a classic and widely used method to examine the potential failure modes in rock masses. The accuracy of planar sliding kinematic analysis is significantly influenced by the value assigned to the lateral limit angle γlim. However, the assignment of γlim is currently used generally based on an empirical criterion. This study aims to propose an approach for determining the value of γlim in deterministic and probabilistic kinematic planar sliding analysis. A new perspective is presented to reveal that γlim essentially influences the probability of forming a potential planar sliding block. The procedure to calculate this probability is introduced using the block theory method. It is found that the probability is correlated with the number of discontinuity sets presented in rock masses. Thus, different values of γlim for rock masses with different sets of discontinuities are recommended in both probabilistic and deterministic planar sliding kinematic analyses; whereas a fixed value of γlim is commonly assigned to different types of rock masses in traditional method. Finally, an engineering case was used to compare the proposed and traditional kinematic analysis methods. The error rates of the traditional method vary from 45% to 119%, while that of the proposed method ranges between 1% and 17%. Therefore, it is likely that the proposed method is superior to the traditional one.

Abstract Objective This study aims to explore the regulatory mechanism of long noncoding RNA X inactive specific transcript (lncRNA XIST) in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). hDPSCs were obtained from freshly extracted third molars and identified by flow cytometry. Methodology Odontogenic differentiation was induced in mineralized culture medium, and hDPSCs were infected with shRNA lentivirus targeting XIST or fused in sarcoma (FUS), followed by detection of alkaline phoshpatase (ALP) activity, alizarin red staining of mineralized nodules, Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) quantification of XIST expression, and Western blot analysis of FUS, ZBTB16, and odontogenic differentiation markers (DSPP and DMP1). IF-FISH was performed to detect the cellular localization of XIST and FUS. RIP assay validated the XIST and FUS binding. ZBTB16 mRNA stability was tested after actinomycin D treatment. hDPSCs were infected with oe-ZBTB16 lentivirus and further treated with sh-XIST for a combined experiment. Results LncRNA XIST was highly expressed in hDPSCs with odontogenic differentiation. Downregulation of XIST or FUS weakened the ALP activity of hDPSCs, reduced mineralized nodules, diminished DSPP and DMP1 expressions. XIST binds to FUS to stabilize ZBTB16 mRNA and promote ZBTB16 expression. ZBTB16 overexpression partially reversed the inhibitory effect of XIST silencing on odontogenic differentiation of hDPSCs. Conclusion In conclusion, XIST stabilizes ZBTB16 mRNA and promotes ZBTB16 expression by binding to FUS, thereby facilitating the odontogenic differentiation of hDPSCs.

Abstract Background The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck’s adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC). Results We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIβ, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model. Conclusions These observations supported the hypothesis that duck’s adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.

The interaction between influenza A virus (IAV) and host proteins is an important process that greatly influences viral replication and pathogenicity. PB2 protein is a subunit of viral ribonucleoprotein (vRNP) complex playing distinct roles in viral transcription and replication. BAG6 (BCL2-associated athanogene 6) as a multifunctional host protein participates in physiological and pathological processes. Here, we identify BAG6 as a new restriction factor for IAV replication through targeting PB2. For both avian and human influenza viruses, overexpression of BAG6 reduced viral protein expression and virus titers, whereas deletion of BAG6 significantly enhanced virus replication. Moreover, BAG6-knockdown mice developed more severe clinical symptoms and higher viral loads upon IAV infection. Mechanistically, BAG6 restricted IAV transcription and replication by inhibiting the activity of viral RNA-dependent RNA polymerase (RdRp). The co-immunoprecipitation assays showed BAG6 specifically interacted with the N-terminus of PB2 and competed with PB1 for RdRp complex assembly. The ubiquitination assay indicated that BAG6 promoted PB2 ubiquitination at K189 residue and targeted PB2 for K48-linked ubiquitination degradation. The antiviral effect of BAG6 necessitated its N-terminal region containing a ubiquitin-like (UBL) domain (17-92aa) and a PB2-binding domain (124-186aa), which are synergistically responsible for viral polymerase subunit PB2 degradation and perturbing RdRp complex assembly. These findings unravel a novel antiviral mechanism via the interaction of viral PB2 and host protein BAG6 during avian or human influenza virus infection and highlight a potential application of BAG6 for antiviral drug development.

Based on undrained cyclic simple shear tests conducted on coastal tidal soft soil under various conditions of cyclic stress ratios and moisture contents, this study investigated the influence of these factors on the dynamic properties of the soil. The findings indicated that with increasing moisture content and stress cycle ratio, the stress–strain hysteresis loop gradually expanded, resulting in a higher strain difference and a transition from a dense to a sparse curve pattern. Moreover, the symmetry of the hysteresis loop was lost in the later stages of shearing. With an increase in the number of cycles, the cumulative shear strain gradually increased, and the increase in the cyclic ratio of water content to stress reduced the number of cyclic shear cycles required to achieve failure, thereby accelerating the soil’s failure rate. A predictive formula was developed based on the experimental results to estimate the failure cycles as a function of the cyclic stress ratio and moisture content. Furthermore, the softening index decreased gradually with an increasing number of cycles, and a higher moisture content and cyclic stress ratio accelerated the soil’s softening process. It was observed that under the conditions of optimal moisture content, the soil exhibited a slower softening rate during the initial stage of shearing.

Two novel reassortant highly pathogenic avian influenza viruses (H5N1) clade 2.3.4.4b.2 were identified in dead migratory birds in China in November 2021. The viruses probably evolved among wild birds through different flyways connecting Europe and Asia. Their low antigenic reaction to vaccine antiserum indicates high risks to poultry and to public health.

ABSTRACTLive poultry markets (LPMs) are regarded as hubs for avian influenza virus (AIV) transmission in poultry and are a major risk factor in human AIV infections. We performed an AIV surveillance study at a wholesale LPM, where different poultry species were sold in separate stalls, and nine retail LPMs, which received poultry from the wholesale LPM but where different poultry species were sold in one stall, in Guangdong province from 2017 to 2019. A higher AIV isolation rate was observed at the retail LPMs than the wholesale LPM. H9N2 was the dominant AIV subtype and was mainly present in chickens and quails. The genetic diversity of H9N2 viruses was greater at the retail LPMs, where a complex system of two-way transmission between different poultry species had formed. The isolated H9N2 viruses could be classed into four genotypes: G57 and the three novel genotypes, NG164, NG165, and NG166. The H9N2 AIVs isolated from chickens and quails at the wholesale LPM only belonged to the G57 and NG164 genotypes, respectively. However, the G57, NG164, and NG165 genotypes were identified in both chickens and quails at the retail LPMs. We found that the replication and transmission of the NG165 genotype were more adaptive to both poultry and mammalian models than those of its precursor genotype, NG164. Our findings revealed that mixed poultry selling at retail LPMs has increased the genetic diversity of AIVs, which might facilitate the emergence of novel viruses that threaten public health.

This paper proposes an inverse method for improving the prediction of tunnel displacements during adjacent excavation. In this framework, staged data assimilation and parameter identification are conducted using the multi-objective particle swarm optimization algorithm. Recent monitoring data are assumed to be more informative and assigned more weights in the multi-objective optimization to improve the prediction accuracy. Then, an empirical formula is applied to correct the time effect of tunnel displacement. The Kriging method is introduced to surrogate the finite element model to reduce computational cost. The proposed framework is verified using a typical staged “excavation nearing tunnel” case. The predictions using the updated parameters are in good agreement with the measurements. The identified values of underlying soil parameters are within the typical ranges for the unloading condition. The updated time effect indicates that tunnel displacements may develop excessively in the three months after the region S1-B is excavated to the bottom. The maximum vertical tunnel displacement may increase from the currently measured 12 mm to the calculated 26 mm if the later construction is suspended long enough. Subsequent constructions need to be timely conducted to restrain the time effect and control tunnel displacements.

Influenza A viruses in animal reservoirs repeatedly cross species barriers to infect humans. Dogs are the closest companion animals to humans, but the role of dogs in the ecology of influenza viruses is unclear. H3N2 avian influenza viruses were transmitted to dogs around 2006 and have formed stable lineages. The long-term epidemic of avian-origin H3N2 virus in canines offers the best models to investigate the effect of dogs on the evolution of influenza viruses. Here, we carried out a systematic and comparative identification of the biological characteristics of H3N2 canine influenza viruses (CIVs) isolated worldwide over 10 years. We found that, during adaptation in dogs, H3N2 CIVs became able to recognize the human-like SAα2,6-Gal receptor, showed gradually increased hemagglutination (HA) acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplets in a ferret model. We also found that human populations lack immunity to H3N2 CIVs, and even preexisting immunity derived from the present human seasonal influenza viruses cannot provide protection against H3N2 CIVs. Our results showed that canines may serve as intermediates for the adaptation of avian influenza viruses to humans. Continuous surveillance coordinated with risk assessment for CIVs is necessary.

Understanding the stability of the seabed foundation holds paramount significance in guaranteeing the safety and structural soundness of the breakwater alongside additional offshore structures. This study aimed to investigate the stability of a sandy seabed foundation around a semi-circular breakwater under wave loading in nearshore areas. A coupled numerical model of waves, a semi-circular breakwater, and the seabed was developed based on the OpenFOAM platform. The VARANS equations were used to govern the wave behavior. Meanwhile, the Biot’s partially dynamic model was employed to numerically simulate the seabed response considering both consolidation under self-weight and dynamic response under wave loading. The effects of various wave parameters, seabed properties, and the radius of the structure on the dynamic response of the seabed and the depth of liquefaction were investigated. The numerical results indicate that an increase in wave height, period, and permeability coefficient intensifies the dynamic response of the seabed soil. Furthermore, an increase in water depth weakened the soil’s dynamic response. There was a negative correlation between the radius of the semi-circular breakwater and the dynamic response. The influence of Poisson’s ratio on the dynamic response of the seabed was relatively small. Furthermore, a stronger dynamic pore pressure response was observed at the connection between the semi-circular breakwater and the rubble foundation.

Since natural fractures are often non-equidimensional, the circular disc model still has great limitations. By contrast, the elliptical disc model is more applicable to representing natural fractures, especially for slender ones. This paper developed a universal elliptical disc (UED) model by incorporating the center point, size, and azimuth of fractures as variables. Specifically, with respect to the azimuth of elliptical fractures in three-dimensional (3D) space, we proposed a paradigm to construct its probability density function (PDF) by coupling the orientation and rotation angle of long axis based on three coordinate transformations. To illustrate the construction process of the PDF of the fracture azimuth, we took the orientation following the Fisher distribution and the rotation angle following Von Mises distribution as an example. A rock slope is used to show the use of the developed UED model, and the 3D DFNs for the slope rock mass are generated by Monte Carlo simulation. In addition, the DFNs for the rock mass are also generated based on the existing circular disc model and non-universal elliptical disc model. The comparison results from the three models clearly illustrate the superiority of the UED model over the existing circular and non-universal elliptical disc models.

Standard penetration test (SPT) has been widely used in offshore exploration because of its unique advantages. Unlike onshore exploration, offshore construction areas are characterized by high waves and water depths ranging from several meters to tens of meters. As a result, the reliability of offshore SPT is significantly reduced compared with onshore SPT. Currently, the probe rod length correction of SPT is not involved in geotechnical engineering investigation codes and related research, which greatly limits the application of this method in offshore exploration. Therefore, a series of SPTs were carried out in offshore environments with different water depths, with a maximum rod length of 65 m. The acceleration and axial stress at each test point of the rod were monitored by the dynamic signal data acquisition system, and the hammer impacting energy at each test point was obtained by Force–Velocity (F-V) method. The test results show that the correction of the rod length of the offshore SPT is different from that of the traditional SPT, and it needs to be further corrected for the water depth. In this paper, a modified method of rod length for offshore SPT is proposed, which can provide reference for the application of offshore SPT.

Abstract Splicing of influenza A virus (IAV) RNA is an essential process in the viral life cycle that involves the co‐opting of host factors. Here, it is demonstrated that induction of host serine and arginine‐rich splicing factor 5 (SRSF5) by IAV facilitated viral replication by enhancing viral M mRNA splicing. Mechanistically, SRSF5 with its RRM2 domain directly bounds M mRNA at conserved sites (M mRNA position 163, 709, and 712), and interacts with U1 small nuclear ribonucleoprotein (snRNP) to promote M mRNA splicing and M2 production. Mutations introduced to the three binding sites, without changing amino acid code, significantly attenuates virus replication and pathogenesis in vivo. Likewise, SRSF5 conditional knockout in the lung protects mice against lethal IAV challenge. Furthermore, anidulafungin, an approved antifungal drug, is identified as an inhibitor of SRSF5 that effectively blocks IAV replication in vitro and in vivo. In conclusion, SRSF5 as an activator of M mRNA splicing promotes IAV replication and is a host‐derived antiviral target.

Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phospho-resistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts.

A model of consolidation for a single-drain well under vacuum preloading, based on Biot’s axisymmetric theory and considering the “real strain” hypothesis, was established using the finite element method. Degenerating the consolidation equation of real strain yielded the Barron’s classical free strain and equal strain equations. The free strain and equal strain finite element models were derived by imposing boundary and constraint conditions on the real strain FEM model. The validation of the simulation process confirmed that the numerical model achieved consistent outcomes, with the theoretical values postulating its effectiveness. The real strain model revealed the Mandel–Cryer effect of soil near the vertical drain during the initial vacuum preloading consolidation process, causing the effective stress to increase more than the effective stress generated by the vacuum pressure and leading to a greater reduction in the void ratio. This phenomenon is one of the reasons for clogging during the vacuum preloading process. However, the free strain and equal strain models cannot produce this effect because they cannot describe the coupling between soil deformation and fluid flow. The parameter analysis of the real strain model showed that as Poisson’s ratio for soil decreased, the consolidation rate of soil also decreased, while the Mandel–Cryer effect of soil increased.

Pandemic influenza, typically caused by the reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remains unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive “mixing vessels” for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented.

Lime stabilization is one of the main methods to achieve efficient treatment and resource utilization of waste slurry. This study investigated the compressibility and permeability of lime-stabilized slurry with different granular gradations based on the ultra-low stress consolidation/permeability test and identified the stabilization mechanism of lime-stabilized slurry with high water content by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) tests. The test results indicated that (i) lime-stabilized slurry with high water content showed obvious evidence of remolded yield stress and (ii) the remolded yield stress increased with the increasing lime dosage. Lime was found to induce the flocculation of clay to form aggregates through ion exchange, further stabilizing them through the volcanic ash reaction, thus increasing the remolded yield strength of the stabilized slurry. The remolded yield stress of the Hangzhou stabilized slurry with a 1% lime dosage was shown to increase from 0 kPa to 5.71 kPa, while the compression index CS1 decreased by 68.8%. In addition, the pore volumes and diameters of the soil increased once the flocculation was completed, leading to increased permeability of the stabilized slurry. It was, however, observed that the stabilized slurry permeability did not increase infinitely with the increasing lime dosage, but on the contrary decreased once the lime dosage exceeded a certain threshold value. The permeability of the Hangzhou stabilized slurry was found to be one order of magnitude higher than that of the remolded slurry at the optimal dosage. Whereas for slurry with high clay content, the recommended lime dosage was established to be 2% to reduce its compressibility or enhance its permeability; for slurry with high silt content, the recommended lime dosage was ascertained to be 3%.

Many cellular genes and networks induced in human lung epithelial cells infected with the influenza virus remain uncharacterized. Here, we find that p21 levels are elevated in response to influenza A virus (IAV) infection, which is independent of p53. Silencing, pharmacological inhibition or deletion of p21 promotes virus replication in vitro and in vivo, indicating that p21 is an influenza restriction factor. Mechanistically, p21 binds to the C-terminus of IAV polymerase subunit PA and competes with PB1 to limit IAV polymerase activity. Besides, p21 promotes IRF3 activation by blocking K48-linked ubiquitination degradation of HO-1 to enhance type I interferons expression. Furthermore, a synthetic p21 peptide (amino acids 36 to 43) significantly inhibits IAV replication in vitro and in vivo. Collectively, our findings reveal that p21 restricts IAV by perturbing the viral polymerase complex and activating the host innate immune response, which may aid the design of desperately needed new antiviral therapeutics.

Cement-based grout has been widely used in various civil engineering applications. However, the filtration behaviors of it when grouting the porous geological masses vary a lot under different grouting conditions, which significantly influences its penetration and the enhancement effect. The purpose of this work was to better understand the filtration of cement-based grout in porous sand by conducting a series of visualized laboratory tests and EDTA titration tests. The experimental results show that the cement filtration, including the penetration, retention, and formation of cement filter cake above the grouting body, is collectively influenced by different grouting factors. With the increase of the soil samples’ pore size and the cement slurry’s water-cement ratio, the penetrated distance and amount of cement in sand increase. However, the penetration does not increase monotonically with the grouting pressure. Too excessive grouting pressure (e.g., 300 kPa in this study) accelerates the formation of cement filter cake and thus stops the subsequent cement infiltration. The mechanisms of different filtration behaviors were explained from microscopic particle clogging in the pore throat of the porous media. Furthermore, the reduced permeability of the sand column with the retained cement due to filtration was discussed, and the dewatering phenomenon of the cement slurry after filter cake formation was first revealed.

Large-diameter monopiles have been widely used for constructing offshore wind turbines. The bearing capacity of a monopile foundation is a significant research problem. In this study, a new type of foundation, known as the pile–bucket foundation, was investigated to improve the bearing capacity of monopiles. A finite element software was used for establishing several numerical models of monopile and pile–bucket foundations to analyze the reinforcement afforded by the bucket attached to the monopile foundation. Furthermore, considering that offshore wind turbines are prone to resonance under the excitation of wind and wave loads, the natural frequencies of the monopile and pile–bucket foundations were determined and compared using both analytical and numerical methods. The results show that compared to the monopile foundation, the pile–bucket foundation has a significantly higher bearing capacity, mainly for large bucket diameters. The natural frequencies of the pile–bucket foundations are slightly higher than those of the monopile foundations. The addition of the bucket can effectively improve the natural frequency without changing the diameter of the monopile and thus saving the foundation cost.

Abstract Background H9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages — A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage —and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses. Finding ZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses. Conclusions Different lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.

In this paper, an analytical wave function method was used to calculate the underground train-induced vibrations with the inhomogeneous soils taken into account. The wave function method is suitable for solving dynamic problems of multi-layered soils; therefore, inhomogeneous soils with uncertainty could be achieved by assigning different soil parameters to each soil layer. Based on the method, a half-space dynamic model with a viscoelastic cylinder tunnel was established. The dynamic shear modulus of the soil was the main uncertain variable in this study, and models with different load frequencies are compared to analyze the effect caused by the uncertainty. According to the numerical results, the relationship between the uncertainty of the soil modulus and the dynamic response of the model was given. When the dynamic shear modulus changes randomly with the range of 20%, the vertical displacement of the surface can be from 1.02 to 1.12 times to that in the model where the soil is homogeneous, while the displacement of the tunnel vault is 1.03–1.1 times.

The waveguide traveling-wave power combiner (WTWPC) falls into the category of asymmetrical non-isolated power combiners, and, therefore, the active load modulation occurring within the combiner was investigated. Proper manipulation of active load modulation gave rise to a two-step design method for the combiner. The first step formulated the specifications of the combiner in terms of active load impedance at its input ports, which determined the objective scattering parameters of the combiner, as well as the desired coherent excitation signals. The second step established a versatile equivalent circuit model to provide a mapping relation between the scattering parameters and the physical dimensions of the combiner. The proposed equivalent circuit method not only offered a close-to-reality description of the existing type of traveling-wave power combiners but also broke new ground for combiner variants that accommodate the more general driving amplifiers. A Q-band quasi-planar traveling-wave waveguide spatial combined amplifier was built to demonstrate the proposed method. The measured P-1dB bandwidth of the prototype was 6 GHz (33-39 GHz).

During 2012–2017, we collected throat swabs from dogs in China to characterize canine influenza virus (CIV) A(H3N2) isolates. A new antigenically and genetically distinct CIV H3N2 clade possessing mutations associated with mammalian adaptation emerged in 2016 and replaced previously circulating strains. This clade probably poses a risk for zoonotic infection.

[This corrects the article DOI: 10.1371/journal.ppat.1008062.].

Affected by the mining activities of the working face, the surrounding rock of the roadway is easily deformed and destroyed. For deep buried roadways, the deformation and destruction of the surrounding rock is particularly prominent. Under the influence of in situ stress fluctuation, 3−1103 tailgate of the Hongqinghe coal mine was in a complex stress environment with a maximum stress exceeding 20 MPa. Affected by mining stress, the roadway behind the working face was seriously deformed. In order to alleviate the deformation of the roadway, directional blasting and cutting measures for the 3−1103 tailgate were adopted in this paper. The mechanism of crack propagation in single-row to three-hole directional blasting was revealed by numerical simulation. The blasted rock was divided into three regions according to the crack condition. The numerical analysis of the cutting heights of 0 m, 10 m, 12 m, and 14 m, respectively, showed the stress peaks of different cutting heights and the deformation law of the surrounding rock. The pressure relief effect was the best at 14 m cutting height. At this time, the peak stress was 39 MPa with the smallest roadway deformation. Based on numerical simulation and theoretical analysis results, engineering tests were carried out. Field monitoring showed that the deformation of the roadway was inversely proportional to the roof cutting height. The higher the cutting height is, the more preferential the roadway is to reach the stable state. It can be concluded that directional blasting can change the surrounding rock structure, control the deformation of the roadway, and play a role in pressure relief. It provides a new measure to control roadway deformation.

Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs production by inhibiting the activation of NF-κB and IRF3 signaling. Furthermore, we showed that PGRN directly interacted with NF-κB essential modulator (NEMO) via its Grn CDE domains. We also verified that PGRN recruited A20 to deubiquitinate K63-linked polyubiquitin chains on NEMO at K264. In addition, we found that macrophage played a major source of PGRN during influenza virus infection, and PGRN neutralizing antibodies could protect against influenza virus-induced lethality in mice. Our data identify a PGRN-mediated IFN evasion pathway exploited by influenza virus with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of PGRN in innate immunity.

Influenza H9N2 subtype viruses and their reassortants (such as H7N9) are posing increasing threats to birds and humans in China. During 2009–2013, multiple novel subtype viruses with H9N2 original genes emerged in China. Yet, the genetic evolution of H9N2 viruses in various host organisms in China has not been systematically investigated since 2009. In the present study, we performed large-scale sequence analysis of H9N2 viral genomes from public databases, representing the spectrum of viruses isolated from birds, mammals and humans in China from 1994 to 2013, and updated the clade classification for each segment. We identified 117 distinct genotypes in 730 H9N2 viruses. We analyzed the sequences of all eight segments in each virus and found three important time points: the years 2000, 2006 and 2010. In the periods divided by these years, genotypic diversity, geographic distribution and host range changed considerably. Genotypic diversity fluctuated greatly in 2000 and 2006. Since 2010, a single genotype became predominant in poultry throughout China, and the eastern coastal region became the newly identified epidemic center. Throughout their 20-year prevalence in China, H9N2 influenza viruses have emerged and adapted from aquatic birds to chickens. The minor avian species and wild birds exacerbated H9N2 genotypes by providing diversified genes, and chickens were the most prevalent vector in which the viruses evolved and expanded their prevalence. It is the necessity for surveillance and disease control on live-bird markets, poultry farms and wild-bird habitats in China.Emerging Microbes & Infections (2017) 6, e106; doi:10.1038/emi.2017.94; published online 29 November 2017

Using the foundation pit at the Jianye Road Station of Hangzhou Metro Line 6 as a case study, the deformation characteristics of a foundation pit subjected to asymmetric loads is investigated in this paper using PLAXIS 3D numerical simulation software. The influence of active pressure zone reinforcement, passive pressure zone reinforcement, and increased thickness of the diaphragm wall at the loaded side on the maximum lateral displacement of diaphragm wall retaining structure of foundation pit is also systematically analyzed. The results show that the deformation of the diaphragm walls on both sides of the foundation pit is strongly inconsistent when subjected to asymmetric loads and is affected by the asymmetric load value and its distance to the foundation pit. In order to reduce the lateral deformations of foundation pit subjected to asymmetric load, two displacement control methods are adopted in the numerical simulations. It is shown that reinforcing the active pressure zone can reduce the maximum lateral displacement of the diaphragm wall on the loaded side to a certain extent but the reinforcement should have a certain depth, resulting in poor efficiency. On the other hand, reinforcing the passive pressure zone can effectively reduce the difference in lateral deformation between the two sides of the foundation pit by increasing the depth and width of the reinforcement zones. It is also observed that the increase in the thickness of the diaphragm wall can reduce the adverse effect of asymmetric loads on the foundation pit. The research results can provide reference for using measures to reduce the influence of asymmetric loads.

Host cells develop the OAS/RNase L [2′–5′–oligoadenylate synthetase (OAS)/ribonuclease L] system to degrade cellular and viral RNA, and/or the OASL/RIG-I (2′–5′–OAS like/retinoic acid inducible protein I) system to enhance RIG-I-mediated IFN induction, thus providing the first line of defense against viral infection. The 2′–5′–OAS-like (OASL) protein may activate the OAS/RNase L system using its typical OAS-like domain (OLD) or mimic the K63-linked pUb to enhance antiviral activity of the OASL/RIG-I system using its two tandem ubiquitin-like domains (UBLs). We first describe that divergent avian (duck and ostrich) OASL inhibit the replication of a broad range of RNA viruses by activating and magnifying the OAS/RNase L pathway in a UBL-dependent manner. This is in sharp contrast to mammalian enzymatic OASL, which activates and magnifies the OAS/RNase L pathway in a UBL-independent manner, similar to 2′–5′–oligoadenylate synthetase 1 (OAS1). We further show that both avian and mammalian OASL can reversibly exchange to activate and magnify the OAS/RNase L and OASL/RIG-I system by introducing only three key residues, suggesting that ancient OASL possess 2–5A [px5′A(2′p5′A)n; x = 1-3; n ≥ 2] activity and has functionally switched to the OASL/RIG-I pathway recently. Our findings indicate the molecular mechanisms involved in the switching of avian and mammalian OASL molecules to activate and enhance the OAS/RNase L and OASL/RIG-I pathways in response to infection by RNA viruses.

Vaccination for highly pathogenic avian influenza (HPAI) has been implemented in China for a decade, however, the virus is still present in poultry. A series of recombinant vaccines, Re-1 to Re-7, have been developed and used, and Re-8 will also be used in clinical settings to prevent the prevailing flu strains. The question remains, when can China eradicate the disease? Here, we review the epidemiology of H5 HPAI along with the development, usage and problems of vaccines. Further suggestions for controlling the disease in China are provided.

Virological and serological surveys have documented that H1N1/2009, avian-origin canine H3N2 (cH3N2), seasonal human-origin H3N2 (hH3N2), and equine-origin H3N8 influenza viruses are consistently circulating in dogs. In the present study, a multiplex reverse-transcriptase polymerase chain reaction (mRT-PCR) assay was developed for simultaneous detection and differentiation of these influenza viruses. Four primer sets were designed to target the hemagglutinin genes of H1N1/2009, cH3N2, hH3N2, and H3N8 canine influenza viruses (CIVs). This mRT-PCR assay demonstrated high specificity and sensitivity for the four CIV subtypes. Additionally, mRT-PCR results obtained from 420 clinical samples were consistent with those obtained by the conventional virus isolation method. Our mRT-PCR assay is reliable for clinical diagnosis and rapid identification of CIVs.

The novel H7N9 influenza virus, which has caused severe disease in humans in China, is a reassortant with surface genes derived from influenza viruses in wild birds. This highlights the importance of monitoring influenza viruses in these hosts. However, surveillance of influenza virus in wild birds remains very limited in China. In this study, we isolated four H4N6 avian influenza viruses (AIVs) from mallard ducks in Beijing Wetland Park, which is located on the East Asia-Australasia migratory flyway. The gene segments of these Chinese H4N6 viruses were closest to AIVs in wild birds from Mongolia or the Republic of Georgia, indicating the interregional AIV gene flow among these countries. All of our isolates belonged to a novel genotype that was different from other H4N6 viruses isolated in China. We further evaluated the virulence and transmission of two representative H4N6 strains in mammalian models. We found that both of these H4N6 viruses replicated efficiently in mice without adaptation. Additionally, these two strains had a 100% transmission rate in guinea pigs via direct contact, but they had not acquired respiratory droplet transmissibility. These results reveal the potential threat to human health of H4N6 viruses in migratory birds and the need for enhanced surveillance of AIVs in wild birds.

Based on the V-system, an orthogonal function system over triangular domain, we proposed a retrieval method for 3D model group consisting of several separate parts. The V-system is an efficient tool to precisely represent either continuous or separate geometric objects, which is its striking characteristic. The V-system can transform a 3D object to the frequency domain based on its triangular mesh, and generate related eigenvector which is invariant to rotation, translation, and scaling. With the V-system, we can successfully extend the orthogonal transformation methods widely used in 2D image retrieval to 3D model retrieval. Retrieval experimental results show that the proposed approach is practical and effective; and it has distinct advantage for model group retrieval. Comparing with the existed 3D model retrieval measures which can only be used to retrieve single model, this new approach can be used to retrieve a model group consisting of several separate parts, which is significant and has important application value in the reuse of model groups.

This paper presents a new class of discrete orthogonal moments, W-moments, based on a hybrid orthogonal function system, W-system of degree one. The W-moments have two main advantages, one is computationally simple due to the piecewise linear structure of the basis functions, and the other is the reproducibility, namely shapes and even shape groups can be precisely reconstructed by finite number of the W-moments, due to the orthogonality of the basis functions on a discrete data set. These properties make the W-moments preferable to the conventional moments when used for describing complex shapes consisting of multiple disjointed curves. To evaluate the proposed moments, image retrieval experiments are conducted on MPEG-7 CE2 and a self-constructed trademark data set. In the experiments, the W-moments are first derived from the trademark images, similarity between query image and each trademark in the database is then evaluated using the Euclidean distance between their W-moments feature vectors, and the trademark retrieval is finally accomplished by comparing their similarities. The experimental results show that the moments proposed in this paper give preferable retrieval results in comparison to other five conventional moments, and the W-moments should be feasible and efficient in practical application.

Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus.Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8-10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines.These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus.

A sheet--pile groin composed of two rows of piles connected by sheets has been applied to resist tidal bores. This study develops an analytical framework to thoroughly investigate the dynamic responses of the sheet-- pile groins under tidal bores. The piles are modeled as an Euler--Bernoulli (EB) beam, while the sheet is simulated as a Rayleigh--Love rod and an EB beam considering the vertical flexural inertia effect. The hydrodynamic pressure is calculated by using radiation wave theory. The saturated soil around the piles is described with dynamic Biot's poroelastic theory, while the additional mass model adopts the interaction between the piles. The applicability and correctness of the formulas are verified by comparing them with numerical simulation results. It investigates the influence of water depth, sheet length, pile radius and the ratio of the soil--pile modulus on the dynamic impedance of the sheet--pile groin. Suggestions based on this study are given to guide sheet--pile groin design to avoid the resonance frequency and improve the impedance in practice engineering. [ABSTRACT FROM AUTHOR]