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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.

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]

Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic. [ABSTRACT FROM AUTHOR]

The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use. [ABSTRACT FROM AUTHOR]