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To address limitations in conventional static load tests for composite foundations, a method utilizing an elastic cushion layer is proposed to accurately simulate subgrade behavior, focusing on a highway project in Guangdong Province. Initial finite element calculations justify the elastic cushion layer introduction. Functional correlations are established between the stab deformation of the piles and the thickness, modulus and the pile-soil stress ratio. The reasonable value of the elastic modulus is taken as 4 – 10 MPa when the elastic cushion layer thickness is 60 mm. Lab and field tests of cement fly-ash gravel (CFG) pile composite foundations assess settlement variations and pile-soil stress ratios from the proposed improvements. Results reveal the superior performance of the elastic cushion layer over the sand cushion layer, effectively mimicking embankment subgrade layers and reducing rigid constraints on the loading plate. The elastic cushion layer exhibits a significant stress-regulating effect, allowing the transition from the original "100 – 150 mm sand cushion layer + loading plate" to "less than 100 mm sand cushion layer + 60 mm elastic cushion layer (8 MPa) + loading plate". This adjustment enhances the practical role of the subgrade in the composite foundation, improving the accuracy and feasibility of static load testing methods. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is the causal agent of African swine fever (ASF), which is contagious and highly lethal to domestic pigs and wild boars. The genome of ASFV encodes many proteins important for ASFV life cycle. The functional importance of topoisomerase AsfvTopII has been confirmed by in vivo and in vitro assays, but the structure of AsfvTopII is poorly studied. Here, we report four AsfvTopII complex structures. The ATPase domain structures reveal the detailed basis for ATP binding and hydrolysis, which is shared by AsfvTopII and eukaryotic TopIIs. The DNA-bound structures show that AsfvTopII follows conserved mechanism in G-DNA binding and cleavage. Besides G-DNA, a T-DNA fragment is also captured in one AsfvTopII structure. Mutagenesis and in vitro assays confirm that Pro852 and the T-DNA-binding residue Tyr744 are important for the function of AsfvTopII. Our study not only advances the understanding on the biological function of AsfvTopII, but also provides a solid basis for the development of AsfvTopII-specific inhibitors.African swine fever virus Topoisomerase II (AsfvTopII) is essential for the replication of the virus. Here, the authors present several crystal structures and provide mechanistic insights into substrate binding and cleavage by the AsfvTopII protein. [ABSTRACT FROM AUTHOR]

Mpox virus (MPXV) can cause mpox in humans. Due to its quick and wide spread in the past two years, mpox has turned into a significant public health concern. Helicase E5 is a multi-domain protein; its primer synthesis and DNA unwinding activity are required for genome uncoating and DNA replication of MPXV. However, the in vitro DNA unwinding activity has never been demonstrated. Here, we report the structural and biochemical studies of MPXV E5, showing that the full-length protein adopts an auto-inhibited conformation. Truncation of the N-terminus can recover the in vitro unwinding activity of E5 towards the forked DNA. Further structural analysis reveals that MPXV E5 shares a conserved mechanism in DNA unwinding and primer synthesis with the homologous proteins. These findings not only advance our understanding on the function of MPXV E5, but also provide a solid basis for the development of anti-poxvirus drugs. [ABSTRACT FROM AUTHOR]

Rubble mound breakwater (RMB) is a kind of sloping breakwater built by squeezing silt by riprap, and the effect of squeezing silt by riprap has a significant influence on the stability of RMB. This paper simulated the dynamic process of squeezing silt by riprap based on the particle flow code and studied the influences of the silt mixed sand layer's thickness, the riprap height, and the riprap radius on the depth of squeezing silt. In the squeezing silt test by single riprap, the depth of squeezing silt increases exponentially as the thickness of silt mixed sand layer increases and increases linearly as the riprap height and the riprap radius increase. In the process of squeezing silt by complete ripraps, the depth of squeezing silt increases linearly as the thickness of silt mixed sand layer increases, increases exponentially as the breakwater height increases, and increases quadratically as the maximum riprap radius increases. Besides, through analyzing the vertical displacement curve of the characteristic particles, the process of squeezing silt by riprap is divided into three parts: instantaneously squeezing silt, squeezing silt by kinetic energy transfer, and squeezing silt by the gravity of riprap heap. The mechanism of squeezing silt by riprap is revealed. This study can well guide the riprap construction of RMB and estimate the amount of riprap, which has greatly practical significance. [ABSTRACT FROM AUTHOR]

To investigate the mechanical process that occurs between rocks and tooth hobs, the crushing of sandstone with a tooth hob was simulated using reconstructed multi-mineral mesoscopic numerical models of various grain-sized sandstone samples. When a piece of sandstone is crushed by the tooth of a hob rolling at a constant speed, the resultant reaction forces of the sandstone on the tooth first hinder and then contribute to the rolling of the hob. The absolute value of the longitudinal reaction force is significantly higher than that of the lateral reaction force. Because the tooth was subjected to reaction forces from the sandstone, forces and moments were applied to the hob in order to keep the hob rolling. The applied forces were equal in value and opposite in direction to the reaction forces of the sandstone on the tooth. Three typical curves of the work done by the applied forces and moment were obtained, and the contribution of the applied lateral force and moment to the total work done for crushing sandstones was variable; however, no work was done by the applied longitudinal force. Moreover, the applied longitudinal force and total work were positively correlated with the strength of sandstone samples. The total work, applied forces, and moment increased with the maximum penetration depth of the tooth in the sandstone. [ABSTRACT FROM AUTHOR]

The accuracy of subgrade quality evaluation is important for road safety assessment. Since there is little research work devoted to testing lightweight cellular concrete (LCC) by an ultrasound-based method, the quantitative relation between ultrasonic testing results and the quality of LCC subgrade is not well understood. In this paper, the quality of LCC subgrade was evaluated with respect to compressive strength and crack discrimination. The relation between ultrasonic testing results and LCC quality was explored through indoor tests. Based on the quantitative relation between ultrasonic pulse velocity and compressive strength of LCC, a fitting formula was established. Moreover, after the LCC became cracked, the ultrasonic pulse velocity and ultrasonic pulse amplitude decreased. After determining the lower limiting values of the ultrasonic pulse velocity and ultrasonic pulse amplitude through the statistical data, it could be calculated whether there were cracks in LCC subgrade. The ultrasonic testing results showed that the compressive strength of the LCC subgrade was suitable for purpose and there was no crack in the subgrade. Then core samples were taken from the subgrade. Comparisons between ultrasonic testing results of subgrade and test results of core samples demonstrated a good agreement. [ABSTRACT FROM AUTHOR]

Besides the canonical RNA-based RNase P, pre-tRNA 5'-end processing can also be catalyzed by protein-only RNase P (PRORP). To date, various PRORPs have been discovered, but the basis underlying substrate binding and cleavage by HARPs (homolog of Aquifex RNase P) remains elusive. Here, we report structural and biochemical studies of HARPs. Comparison of the apo- and pre-tRNA-complexed structures showed that HARP is able to undergo large conformational changes that facilitate pre-tRNA binding and catalytic site formation. Planctomycetes bacterium HARP exists as dimer in vitro, but gel filtration and electron microscopy analysis confirmed that HARPs from Thermococcus celer, Thermocrinis minervae and Thermocrinis ruber can assemble into larger oligomers. Structural analysis, mutagenesis and in vitro biochemical studies all supported one cooperative pre-tRNA processing mode, in which one HARP dimer binds pre-tRNA at the elbow region whereas 5'-end removal is catalyzed by the partner dimer. Our studies significantly advance our understanding on pre-tRNA processing by PRORPs. HARP are member of protein-only RNase P, which catalyzes pre-tRNA 5'-end processing and maturation. Here, the authors present crystal structure and provide mechanistic insights into pre-tRNA binding and cleavage by HARP proteins. [ABSTRACT FROM AUTHOR]

Owing to its great threat to human health and environment, Pb2+ pollution has been recognized as a major public problem by the World Health Organization (WHO). Many DNA aptamers have been utilized in the development of Pb2+-detection sensors, but the underlying mechanisms remain elusive. Here, we report three Pb2+-complexed structures of the thrombin binding aptamer (TBA). These high-resolution crystal structures showed that TBA forms intramolecular G-quadruplex and Pb2+ is bound by the two G-tetrads in the center. Compared to K+-stabilized G-quadruplexes, the coordinating distance between Pb2+ and the G-tetrads are much shorter. The T3T4 and T12T13 linkers play important roles in dimerization and crystallization of TBA, but they are changeable for Pb2+-binding. In combination with mutagenesis and CD spectra, the G8C mutant structure unraveled that the T7G8T9 linker of TBA is also variable. In addition to expansion of the Pb2+-binding aptamer sequences, our study also set up one great example for quick and rational development of other aptamers with similar or optimized binding activity. [ABSTRACT FROM AUTHOR]

During the construction of lightweight cellular concrete (LCC), material damage frequently occurs, causing the degradation and deterioration of the mechanical performance, durability, and subgrade quality of LCC. The construction-induced damage can be more significant than those from the service environment of LCC, such as freeze-thaw (F—T) action in cold regions. However, the effect of construction-induced damage on LCC during F—T cycles is often ignored and the deterioration mechanisms are not yet clarified. In this study, we investigated the factors causing damage during construction using a sample preparation method established to simulate the damage in the laboratory setting. We conducted F—T cycle tests and microstructural characterization to study the effect of microstructural damage on the overall strength of LCC with different water contents under F—T actions. We established the relationship between the pore-area ratio and F—T cycle times, pore-area ratio, and strength, as well as the F—T cycle times and strength under different damage forms. The damage evolution is provided with the rationality of the damage equation, verified by comparing the measured and predicted damage variables. This study would serve as a guide for the construction and performance of LCC in cold regions. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is highly contagious and can cause lethal disease in pigs. ASFV is primarily replicated in the cytoplasm of pig macrophages, which is oxidative and caused constant damage to ASFV genome. ASFV AP endonuclease (AsfvAP) catalyzes DNA cleavage reaction at the abasic site and is a key enzyme of ASFV base excision repair (BER) system. Although it plays an essential role in ASFV survival in host cells, the basis underlying substrate binding and cleavage by AsfvAP remains unclear. Here, we reported the structural and functional studies of AsfvAP, showing that AsfvAP adopts a novel DNA-binding mode distinct from other APs. AsfvAP possesses many unique structural features, including one narrower nucleotide-binding pocket at the active site, the C16–C20 disulfide bond-containing region, and histidine-rich loop. As indicated by our mutagenesis, in vitro binding and cleavage assays, these features are important for AsfvAP to suit the acidic and oxidative environment. Owing to their functional importance, these unique features could serve as targets for designing small molecule inhibitors that could disrupt the repair process of ASFV genome and help fight against this deadly virus in the future. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury can result in the decreased quality of life and bring us economic burden on society and individuals. Wallerian degeneration (WD) is critical for nerve degeneration and regeneration, but the mechanisms of WD are still elusive. Here, we report the effect of Toll-like receptor 4 (TLR4) on cultured Schwann cells (SCs) in vitro. The data showed that TLR4 expression was up-regulated after sciatic nerve injury of rat. TLR4 was expressed in cultured SCs. Enhanced or silenced expression of TLR4 affected SC proliferation, migration, apoptosis and relative gene expression. Furthermore, altered expression of TLR4 resulted in expression changes in c-Jun, ERK and catenin but not AKT and c-Fos pathways in SCs. These results suggested that TLR4 may be an important effective target in peripheral nerve degeneration and/or regeneration during WD in future investigations. [ABSTRACT FROM AUTHOR]