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273 result(s) for "Shao, Zhiwei"
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Pathophysiological Mechanisms and Potential Therapeutic Targets in Intracerebral Hemorrhage
Intracerebral hemorrhage (ICH) is a subtype of hemorrhagic stroke with high mortality and morbidity. The resulting hematoma within brain parenchyma induces a series of adverse events causing primary and secondary brain injury. The mechanism of injury after ICH is very complicated and has not yet been illuminated. This review discusses some key pathophysiology mechanisms in ICH such as oxidative stress (OS), inflammation, iron toxicity, and thrombin formation. The corresponding therapeutic targets and therapeutic strategies are also reviewed.
Structure-guided development of Pb2+-binding DNA aptamers
Owing to its great threat to human health and environment, Pb 2+ 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 Pb 2+ -detection sensors, but the underlying mechanisms remain elusive. Here, we report three Pb 2+ -complexed structures of the thrombin binding aptamer (TBA). These high-resolution crystal structures showed that TBA forms intramolecular G-quadruplex and Pb 2+ is bound by the two G-tetrads in the center. Compared to K + -stabilized G-quadruplexes, the coordinating distance between Pb 2+ 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 Pb 2+ -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 Pb 2+ -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.
Crystal structures and insights into precursor tRNA 5’-end processing by prokaryotic minimal protein-only RNase P
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.
Is the Large-scale Structure Traced by the BOSS LOWZ Galaxies Consistent with Planck?
Recently, several studies reported a significant discrepancy between the clustering and lensing of the Baryon Oscillation Spectroscopic Survey (BOSS) galaxies in the Planck cosmology. We construct a simple yet powerful model based on the linear theory to assess whether this discrepancy points toward deviations from Planck. Focusing on scales 10 < R < 30 h −1Mpc, we model the amplitudes of clustering and lensing of BOSS LOWZ galaxies using three parameters: galaxy bias b g; galaxy-matter cross-correlation coefficient r gm; and A, defined as the ratio between the true and Planck values of σ 8. Using the cross-correlation matrix as a diagnostic, we detect systematic uncertainties that drive spurious correlations among the low-mass galaxies. After building a clean LOWZ sample with r gm ∼ 1, we derive a joint constraint of b g and A from clustering+lensing, yielding bg=2.47−0.30+0.36 and A=0.81−0.09+0.10 , i.e., a 2σ tension with Planck. However, due to the strong degeneracy between b g and A, systematic uncertainties in b g could masquerade as a tension with A = 1. To ascertain this possibility, we develop a new method to measure b g from the cluster-galaxy cross correlation and cluster weak lensing using an overlapping cluster sample. By applying the independent bias measurement (b g = 1.76 ± 0.22) as a prior, we successfully break the degeneracy and derive stringent constraints of bg=2.02−0.15+0.16 and A = 0.96 ± 0.07. Therefore, our result suggests that the large-scale clustering and lensing of LOWZ galaxies are consistent with Planck, while the different bias estimates may be related to some observational systematics that need to be mitigated in future surveys.
Structures of African swine fever virus topoisomerase complex and their implications
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 Asfv TopII has been confirmed by in vivo and in vitro assays, but the structure of Asfv TopII is poorly studied. Here, we report four Asfv TopII complex structures. The ATPase domain structures reveal the detailed basis for ATP binding and hydrolysis, which is shared by Asfv TopII and eukaryotic TopIIs. The DNA-bound structures show that Asfv TopII follows conserved mechanism in G-DNA binding and cleavage. Besides G-DNA, a T-DNA fragment is also captured in one Asfv TopII structure. Mutagenesis and in vitro assays confirm that Pro852 and the T-DNA-binding residue Tyr744 are important for the function of Asfv TopII. Our study not only advances the understanding on the biological function of Asfv TopII, but also provides a solid basis for the development of Asfv TopII-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.
Optimizing Foam Lightweight Soil Embankments: Enhancing Stability and Mitigating Settlement in Soft Soil Foundations
Foam lightweight soil (FLS) has emerged as a promising material in geotechnical engineering due to its low density, high load-bearing capacity, and ability to incorporate industrial by-products such as fly ash. It offers significant advantages in mitigating settlement and improving stability for embankments constructed on soft soil foundations. However, the combined influence of key parameters—including layered filling thickness, bulk density, and geogrid reinforcement—on the long-term performance of FLS embankments remains insufficiently understood. This study investigates the settlement behavior and stability of FLS embankments through a combination of field experiments and finite element simulations over a 15-year period. The results indicate that layered filling thicknesses of 500–600 mm achieve the best balance between settlement control and construction feasibility. When the thickness exceeds 800 mm, not only does the uniformity deteriorate, but the settlement also increases. Experimental results showed that a medium bulk density of 6 to 8 kN/m3 is optimal as a balance between strength and settlement behavior. Furthermore, geogrid reinforcement significantly improved stability, with safety factors increasing by up to 1.87 compared to unreinforced sections. The findings provide practical guidelines for the design and construction of FLS embankments, particularly for bridge approaches and soft soil foundations. In addition to improving structural performance, the incorporation of industrial by-products highlights the potential of FLS as a sustainable and cost-effective material for future infrastructure development.
Abnormal levels of expression of microRNAs in peripheral blood of patients with traumatic brain injury are induced by microglial activation and correlated with severity of injury
Background Microglia play a crucial role in regulating the progression of traumatic brain injury (TBI). In specific, microglia can self-activate and secrete various substances that exacerbate or alleviate the neuroimmune response to TBI. In addition, microRNAs (miRNAs) are involved in the functional regulation of microglia. However, molecular markers that reflect the dynamics of TBI have not yet been found in peripheral tissues. Methods Paired samples of peripheral blood were collected from patients with TBI before and after treatment. Next-generation sequencing and bioinformatics analysis were used to identify the main pathways and biological functions of TBI-related miRNAs in the samples. Moreover, lipopolysaccharide-treated human microglia were used to construct a cellular immune-activation model. This was combined with analysis of peripheral blood samples to screen for highly expressed miRNAs derived from activated microglia after TBI treatment. Quantitative reverse-transcriptase polymerase chain reaction was used to determine the expression levels of these miRNAs, allowing their relationship with the severity of TBI to be examined. Receiver operating characteristic (ROC) curves were constructed to analyse the clinical utility of these miRNAs for determining the extent of TBI. Results Sequencing results showed that 37 miRNAs were differentially expressed in peripheral blood samples from patients with TBI before and after treatment, with 17 miRNAs being upregulated and 20 miRNAs being downregulated after treatment. The expression profiles of these miRNAs were verified in microglial inflammation models and in the abovementioned peripheral blood samples. The results showed that hsa-miR-122-5p and hsa-miR-193b-3p were highly expressed in the peripheral blood of patients with TBI after treatment and that the expression levels of these miRNAs were correlated with the patients’ scores on the Glasgow Coma Scale. ROC curve analysis revealed that abnormally high levels of expression of hsa-miR-122-5p and hsa-miR-193b-3p in peripheral blood have some clinical utility for distinguishing different extents of TBI and thus could serve as biomarkers of TBI. Conclusion Abnormally high levels of expression of hsa-miR-122-5p and hsa-miR-193b-3p in the peripheral blood of patients with TBI were due to the activation of microglia and correlated with the severity of TBI. This discovery may help to increase understanding of the molecular pathology of TBI and guide the development of new strategies for TBI therapy based on microglial function.
Super Hydrophobic UHMWPE/PTFE/PVA Composites with Low Friction: Preparation and Wear Mechanism
This study develops novel superhydrophobic UHMWPE/PTFE/PVA composites via hot-pressing sintering to achieve ultra-low friction and enhanced wear resistance. The ternary system synergistically combines UHMWPE’s mechanical stability, PTFE’s lubricity, and PVA’s dispersion/binding capability. Results show PTFE disrupts UHMWPE crystallization, reducing melting temperature by 2.77 °C and enabling energy dissipation. All composites exhibit hydrophobicity, with optimal formulations (UPP3/UPP4) reaching superhydrophobicity. Tribological testing under varied loads and frequencies reveals low friction, where UPP1 achieves a COF of 0.043 and wear rate below 1.5 × 10−5 mm3/(N·m) under low-load conditions. UHMWPE oxidative degradation forming carboxylic acids at the interface (C=O at 289 eV, C–O at 286 eV). Formation of tungsten oxides (WO3/WO2), carbides (WC), and transfer films on steel counterparts. A four-step tribochemical reaction pathway is established. PVA promotes uniform transfer films, while PTFE lamellar peeling and UHMWPE chain stability enable sustained lubrication. Carbon-rich stratified accumulations under high-load/speed increase COF via abrasive effects. The composites demonstrate exceptional biocompatibility and provide a scalable solution for biomedical and industrial tribological applications.
Defect Signal Identification in Concrete-Filled Steel Tubular Columns Based on Wavelet Analysis
Based on the principle of acoustic energy distribution at a single flat interface under vertical ultrasonic incidence, this study derives the reflection and transmission coefficients for both healthy bonding interfaces and debonded interfaces in concrete-filled steel tubular (CFST) columns. The calculation results indicate that when debonding defects occur in CFST, the signal amplitude received by the transducer on the same side increases significantly. By applying wavelet denoising and wavelet packet energy calculation methods to the experimental study of debonding damage identification at CFST interfaces, the area and extent of debonding defects can be accurately predicted.
Ultrasonic Damage Detection of Composite Panels Based on Wavelet Analysis
The common types of damage in sandwich panels during normal use include: core seam damage, delamination caused by adhesive aging due to alternating hot and cold temperatures, and indentation damage caused by impact. Such damages can weaken the load-bearing capacity of sandwich panels. If not identified promptly, they may result in accidents and potential injuries. In this study, a non-metallic ultrasonic testing device was used to detect various types of damage in the sandwich panels, and wavelet analysis theory was applied to process the experimental data.