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

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

Nitrogen-doped micropores binder-free carbon-sulphur composites as the cathode for long-life lithium-sulphur batteries

Nitrogen-doped micropores-contained carbon nanofibres (NMCNFs) were prepared by carbonizing ZIF-8 grown in liquid-phase along with electrospinning. When NMCNFs act as sulphur host materials in lithium–sulphur batteries, NMCNFs can retard the shuttle effect and dissolution of polysulfides through the synergic action of effective physical confinement to micropores and nitrogen surface chemical absorption. NMCNFs show a capacity up to 636 mAh g−1 after 500 cycles against Li anode

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

Recombinase polymerase amplification combined with lateral flow biosensor for rapid visual detection of Clostridium perfringens in chicken meat and milk

AimsClostridium perfringens is one of the major anaerobic pathogen causing food poisoning and animal enteritis. With the rise of antibiotic resistance and the restrictions of the use of antibiotic growth promoting agents (AGPs) in farming, Clostridium enteritis and food contamination have become more common. It is time-consuming and labor-intensive to confirm the detection by standard culture methods, and it is necessary to develop on-site rapid detection tools. In this study, a combination of recombinase polymerase amplification (RPA) and lateral flow biosensor (LFB) was used to visually detect C. perfringens in chicken meat and milk.Methods and resultsTwo sets of primers were designed for the plc gene of C. perfringens, and the amplification efficiency and specificity of the primers. Selection of primers produces an amplified fragment on which the probe is designed. The probe was combined with the lateral flow biosensor (LFB). The reaction time and temperature of RPA-LFB assay were optimized, and the sensitivity of the assay was assessed. Several common foodborne pathogens were selected to test the specificity of the established method. Chicken and milk samples were artificially inoculated with different concentrations (1 × 102 CFU/mL to 1 × 106 CFU/mL) of C. perfringens, and the detection efficiency of RPA-LFB method and PCR method was compared. RPA-LFB can be completed in 20 min and the results can be read visually by the LFB test strips. The RPA-LFB has acceptable specificity and the lowest detection limit of 100 pg./μL for nucleic acid samples. It was able to stably detect C. perfringens contamination in chicken and milk at the lowest concentration of 1 × 104 CFU/mL and 1 × 103 CFU/mL, respectively.ConclusionIn conclusion, RPA-LFB is specific and sensitive. It is a rapid, simple and easy-to-visualize method for the detection of C. perfringens in food and is suitable for use in field testing work

Experimental Study on Failure Model of Tailing Dam Overtopping under Heavy Rainfall

AbstractUnusual rainfall is the primary cause of the failure of the tailing dams, and overtopping is the most representative model of the tailing dam failure. The upstream tailing dam was selected as the research object to study the whole process of breach extension and the overtopping dam-failure mechanism under the full-scale rainfall condition. The results showed that the significant size grading phenomenon in the front, middle, and end of the tailing pond was obvious due to the flow separation effect, and its average particle diameter was D50. At different moments of rainfall, the height of the infiltration line at different positions of the dam body was different; at the rainfall of 3600 s, the height of the infiltration line lagged behind the height of the tailing pond, and this phenomenon from the tail of pond to the outside of the dam slope became more obvious. After the rainfall of 3600 s, the height of the infiltration line lagging behind the water level in the pond basically disappeared, and the rate of infiltration line rise kept pace with the rate of water level. The process of overtopping dam-failure experienced dam overtopping (gully erosion), formation of a multistepped small “scarp,” breach rapid expansion, formation of large “scarp,” and burst (fan-shaped formation). The width and depth of the breach showed a positive correlation, and the widening rate of the breach was 3 to 8 times of the deepening rate, especially in the middle of the dam break, widening behavior occupied the dominant factor. The shape of the dam body after failure was parabolic, and the dam body had obvious elevation changes. These results provide the theoretical guidance and engineering application value for improving the theory and early warning model of the upstream tailing dam

Mutations in the Human naked cuticle Homolog NKD1 Found in Colorectal Cancer Alter Wnt/Dvl/β-Catenin Signaling

BACKGROUND:Mutation of Wnt signal antagonists Apc or Axin activates beta-catenin signaling in many cancers including the majority of human colorectal adenocarcinomas. The phenotype of apc or axin mutation in the fruit fly Drosophila melanogaster is strikingly similar to that caused by mutation in the segment-polarity gene, naked cuticle (nkd). Nkd inhibits Wnt signaling by binding to the Dishevelled (Dsh/Dvl) family of scaffold proteins that link Wnt receptor activation to beta-catenin accumulation and TCF-dependent transcription, but human NKD genes have yet to be directly implicated in cancer. METHODOLOGY/PRINCIPAL FINDINGS:We identify for the first time mutations in NKD1--one of two human nkd homologs--in a subset of DNA mismatch repair-deficient colorectal tumors that are not known to harbor mutations in other Wnt-pathway genes. The mutant Nkd1 proteins are defective at inhibiting Wnt signaling; in addition, the mutant Nkd1 proteins stabilize beta-catenin and promote cell proliferation, in part due to a reduced ability of each mutant Nkd1 protein to bind and destabilize Dvl proteins. CONCLUSIONS/SIGNIFICANCE:Our data raise the hypothesis that specific NKD1 mutations promote Wnt-dependent tumorigenesis in a subset of DNA mismatch-repair-deficient colorectal adenocarcinomas and possibly other Wnt-signal driven human cancers

OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

AbstractGenerating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo

Regulation of T cell receptor signaling by activation-induced zinc influx

Zinc enhances TCR signaling in part by inhibiting Shp-1 recruitment to the TCR synapse

Stem Cells for Huntington's Disease (SC4HD): An International Consortium to Facilitate Stem Cell-Based Therapy for Huntington's Disease

Huntington's disease (HD) research is entering an exciting phase, with new approaches such as huntingtin lowering strategies and cell therapies on the horizon. Technological advances to direct the differentiation of stem cells to desired neural types have opened new strategies for restoring damaged neuronal circuits in HD. However, challenges remain in the implementation of cell therapy approaches for patients suffering from HD. Cell therapies, together with other invasive approaches including allele specific oligonucleotides (ASOs) and viral delivery of huntingtin-lowering agents, require direct delivery of the therapeutic agents locally into the brain or cerebrospinal fluid. Delivering substances directly into the brain is complex and presents multiple challenges, including those related to regulatory requirements, safety and efficacy, surgical instrumentation, trial design, patient profiles, and selection of suitable and sensitive primary and secondary outcomes. In addition, production of clinical grade cell-based medicinal products also requires adherence to regulatory standards with extensive quality control of the protocols and cell products across different laboratories and production centers. Currently, there is no consensus on how best to address these challenges. Here we describe the formation of Stem Cells For Huntington's Disease (SC4HD: https://www.sc4hd.org/), a network of researchers and clinicians working to develop guidance and greater standardization for the HD field for stem cell based transplantation therapy for HD with a mission to work to develop criteria and guidance for development of a neural intra-cerebral stem cell-based therapy for HD