Study on dynamic strength and liquefaction mechanism of silt soil in Castor earthquake prone areas under different consolidation ratios

Under the Castor earthquake, there is a risk of liquefaction instability of saturated tailings, and the evolution of dynamic pore pressure can indirectly reflect its instability process. Before applying dynamic loads, the static stress state of soil is one of the main factors affecting the development of soil dynamic strength and dynamic pore pressure, and there are significant differences in soil dynamic strength under different consolidation ratios. This paper conducted dynamic triaxial tests on saturated tailings silt with different consolidation ratios, and analyzed the dynamic strength variation and liquefaction mechanism of the samples using the discrete element method (PFC3D). The results showed that 1) as the Kc′ gradually increased, and there was a critical consolidation ratio Kc′ during the development of the dynamic strength of the sample. The specific value of Kc′ was related to the properties and stress state of saturated sand. The Kc′ in this research was about 1.9. When Kc < 1.9, dynamic strength was increased with the increase in Kc; when Kc > 1.9, dynamic strength was decreased with the Kc. 2) Under the impact of cyclic load, when samples were normally consolidated (Kc =1), the pore water pressure would tend to be equal to the confining pressure to cause soil liquefaction. In the case of eccentric consolidation (Kc > 1), the pore water pressure would be less than the confining pressure, thus, the soil liquefaction would not be induced, and the pore pressure value would decrease with the increase of consolidation ratio. This paper provides engineering guidance value for the study of dynamic strength and liquefaction mechanism of tailings sand and silt in Castor earthquake prone areas under different consolidation ratios

Endothelial cells derived from patients' induced pluripotent stem cells for sustained factor VIII delivery and the treatment of hemophilia A.

Hemophilia A (HA) is a bleeding disorder characterized by spontaneous and prolonged hemorrhage. The disease is caused by mutations in the coagulation factor 8 gene (F8) leading to factor VIII (FVIII) deficiency. Since FVIII is primarily produced in endothelial cells (ECs) in a non-diseased human being, ECs hold great potential for development as a cell therapy for HA. We showed that HA patient-specific induced pluripotent stem cells (HA-iPSCs) could provide a renewable supply of ECs. The HA-iPSC-derived ECs were transduced with lentiviral vectors to stably express the functional B domain deleted F8 gene, the luciferase gene, and the enhanced green fluorescent protein gene (GFP). When transplanted intramuscularly into neonatal and adult immune deficient mice, the HA-iPSC-derived ECs were retained in the animals for at least 10-16 weeks and maintained their expression of FVIII, GFP, and the endothelial marker CD31, as demonstrated by bioluminescence imaging and immunostaining, respectively. When transplanted into HA mice, these transduced HA-iPSC-derived ECs significantly reduced blood loss in a tail-clip bleeding test and produced therapeutic plasma levels (11.2%-369.2%) of FVIII. Thus, our studies provide proof-of-concept that HA-iPSC-derived ECs can serve as a factory to deliver FVIII for the treatment of HA not only in adults but also in newborns

Synthesis of Alkyl Substituted Dicyclohexano-18-crown-6 Homologues for Strontium Extraction in HNO3 Media

AbstractA series of dicyclohexano-18-crown-6 (DCH18C6) homologues containing different alkyl substituents were synthesized for a comparative study of the extraction ability towards strontium. The synthesis and the structure characterization of the intermediates and the products were detailed. The crown ether homologues were labeled as CX-DCH18C6 (X=3∼7), where the X represents the number of the carbon atoms in the alkyl substituents. The extraction ability of the CX-DCH18C6 samples towards strontium in solvent extraction system was investigated. The substituent effect of the samples was discussed, and the factors affecting the separation such as solvent, acidity and initial metal concentration were examined

Comparative Proteomic Analysis of Streptococcus suis Biofilms and Planktonic Cells That Identified Biofilm Infection-Related Immunogenic Proteins

Streptococcus suis (SS) is a zoonotic pathogen that causes severe disease symptoms in pigs and humans. Biofilms of SS bind to extracellular matrix proteins in both endothelial and epithelial cells and cause persistent infections. In this study, the differences in the protein expression profiles of SS grown either as planktonic cells or biofilms were identified using comparative proteomic analysis. The results revealed the existence of 13 proteins of varying amounts, among which six were upregulated and seven were downregulated in the Streptococcus biofilm compared with the planktonic controls. The convalescent serum from mini-pig, challenged with SS, was applied in a Western blot assay to visualize all proteins from the biofilm that were grown in vitro and separated by two-dimensional gel electrophoresis. A total of 10 immunoreactive protein spots corresponding to nine unique proteins were identified by MALDI-TOF/TOF-MS. Of these nine proteins, five (Manganese-dependent superoxide dismutase, UDP-N-acetylglucosamine 1-carboxyvinyltransferase, ornithine carbamoyltransferase, phosphoglycerate kinase, Hypothetical protein SSU05_0403) had no previously reported immunogenic properties in SS to our knowledge. The remaining four immunogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, hemolysin, pyruvate dehydrogenase and DnaK) were identified under both planktonic and biofilm growth conditions. In conclusion, the protein expression pattern of SS, grown as biofilm, was different from the SS grown as planktonic cells. These five immunogenic proteins that were specific to SS biofilm cells may potentially be targeted as vaccine candidates to protect against SS biofilm infections. The four proteins common to both biofilm and planktonic cells can be targeted as vaccine candidates to protect against both biofilm and acute infections

Immunoproteomic analysis of bacterial proteins of Actinobacillus pleuropneumoniae serotype 1

<p>Abstract</p> <p>Background</p> <p><it>Actinobacillus pleuropneumoniae </it>(APP) is one of the most important swine pathogens worldwide. Identification and characterization of novel antigenic APP vaccine candidates are underway. In the present study, we use an immunoproteomic approach to identify APP protein antigens that may elicit an immune response in serotype 1 naturally infected swine and serotype 1 virulent strain S259-immunized rabbits.</p> <p>Results</p> <p>Proteins from total cell lysates of serotype 1 APP were separated by two-dimensional electrophoresis (2DE). Western blot analysis revealed 21 immunoreactive protein spots separated in the pH 4-7 range and 4 spots in the pH 7-11 range with the convalescent sera from swine; we found 5 immunoreactive protein spots that separated in the pH 4-7 range and 2 in the pH 7-11 range with hyperimmune sera from S259-immunized rabbits. The proteins included the known antigens ApxIIA, protective surface antigen D15, outer membrane proteins P5, subunit NqrA. The remaining antigens are being reported as immunoreactive proteins in APP for the first time, to our knowledge.</p> <p>Conclusions</p> <p>We identified a total of 42 immunoreactive proteins of the APP serotype 1 virulent strain S259 which represented 32 different proteins, including some novel immunoreactive factors which could be researched as vaccine candidates.</p

The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner

SummaryReprogramming of somatic cells into induced pluripotent stem cells (iPSCs) resets the epigenome to an embryonic-like state. Vitamin C enhances the reprogramming process, but the underlying mechanisms are unclear. Here we show that the histone demethylases Jhdm1a/1b are key effectors of somatic cell reprogramming downstream of vitamin C. We first observed that vitamin C induces H3K36me2/3 demethylation in mouse embryonic fibroblasts in culture and during reprogramming. We then identified Jhdm1a/1b, two known vitamin-C-dependent H3K36 demethylases, as potent regulators of reprogramming through gain- and loss-of-function approaches. Furthermore, we found that Jhdm1b accelerates cell cycle progression and suppresses cell senescence during reprogramming by repressing the Ink4/Arf locus. Jhdm1b also cooperates with Oct4 to activate the microRNA cluster 302/367, an integral component of the pluripotency machinery. Our results therefore reveal a role for H3K36me2/3 in cell fate determination and establish a link between histone demethylases and vitamin-C-induced reprogramming

Research on the Macro-Mesoscopic Response Mechanism of Multisphere Approximated Heteromorphic Tailing Particles

AbstractThe shape of tailing particles is essential factors of their macroscopic mechanical properties. Scholars have studied the effects of controllable factors, such as loading method, confining pressure, and strain rate, on the strength of tailing sand. However, research on the tailing particle structure and shape through laboratory tests has proved to be difficult due to the uncertain and discrete tailing particle distribution. Thus, the macro-mesoscopic response of heteromorphic tailing particles is rarely investigated. In this paper, the macro-mesoscopic response of heteromorphic tailing particles is studied using multisphere approximation, and numerical simulation of triaxial tests on the particles is conducted. Nonlinear evolution patterns of porosity, internal friction angle, and cohesion of heteromorphic tailing particles with the variation of angularity were investigated using the flexible boundary program developed in this study, which revealed the intrinsic relationship between the mesostructure evolution mechanism and the macroscopic engineering characteristics of heteromorphic tailing particles. The research results showed that (1) changes in angularity led to tailing particle rearrangements and, in turn, porosity changes. With increased angularity and confining pressure, particle sphericity decreased, and the deviatoric and peak stress increased accordingly. In the meantime, the softening was more significant as the peak stress was exceeded, while the cohesive force generally increased. (2) With fixed particle shape and angularity, the internal friction angle decreased slightly as the effective confining pressure increased. (3) In the shearing process, the simulated contact force chain evolution of tailing particles with different shapes was similar. The disordered contact force chains gradually undergo directional connection, i.e., the increased confining pressure reduced the number of free tailing particles and increased the number of stressed particles. (4) The triaxial stress-strain and peak stress in rigid boundary simulations under different confining pressures were slightly lower than those in the flexible boundary simulations. However, the difference was insignificant, indicating the good feasibility and reasonability of rigid boundary simulations for the macroscopic mechanical behaviors in triaxial tests. The research results could offer more direct insights into the macro-mesoscopic response and mechanical mechanisms of nonspherical particles and provide references for the simulation of tailings at the microscopic levels

Potential molecular mechanisms of Erlongjiaonang action in idiopathic sudden hearing loss: A network pharmacology and molecular docking analyses

BackgroundIdiopathic sudden hearing loss (ISHL) is characterized by sudden unexplainable and unilateral hearing loss as a clinically emergent symptom. The use of the herb Erlongjiaonang (ELJN) in traditional Chinese medicine is known to effectively control and cure ISHL. This study explored the underlying molecular mechanisms using network pharmacology and molecular docking analyses.MethodThe Traditional Chinese Medicine System Pharmacological database and the Swiss Target Prediction database were searched for the identification of ELJN constituents and potential gene targets, respectively, while ISHL-related gene abnormality was assessed using the Online Mendelian Inheritance in Man and Gene Card databases. The interaction of ELJN gene targets with ISHL genes was obtained after these databases were cross-screened, and a drug component–intersecting target network was constructed, and the gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction networks were analyzed. Cytoscape software tools were used to map the active components–crossover target–signaling pathway network and screened targets were then validated by establishing molecular docking with the corresponding components.ResultErlongjiaonang contains 85 components and 250 corresponding gene targets, while ISHL has 714 disease-related targets, resulting in 66 cross-targets. The bioinformatical analyses revealed these 66 cross-targets, including isorhamnetin and formononetin on NOS3 expression, baicalein on AKT1 activity, and kaempferol and quercetin on NOS3 and AKT1 activity, as potential ELJN-induced anti-ISHL targets.ConclusionThis study uncovered potential ELJN gene targets and molecular signaling pathways in the control of ISHL, providing a molecular basis for further investigation of the anti-ISHL activity of ELJN