Search

Engineering construction in mountainous areas is a key factor inducing slope failure, which poses severe threats to life and property safety during construction and operation. Thus, clear understanding of slope structure and potential failure mechanisms is of great importance for slope reinforcement. The Shangge landslide, located in a mountainous area of Western Henan, China, was triggered by excavation along a toll station. The slope was still unstable after a row of anti-sliding piles were constructed. To clarify the deformation characteristics and failure mechanism of this landslide and provide reinforcement guidance for slopes with similar geological conditions, a combined method of field investigation, displacement monitoring, and numerical simulation was employed. The results indicate that the natural slope comprises a dual structure of soil and rock, and that the soil, with poor permeability and high water moisture, was prone to form a potential sliding surface. Secondly, slope excavation was the direct triggering factor. Lastly, but most importantly, the preliminary investigation work failed to accurately expose the potential position of the sliding surface, and the existing anti-slide piles failed to cross the potential sliding surface, which made them unable to effectively improve slope stability. The numerical simulation verified that the recommended piles installed on the platform of level 2 could significantly improve slope stability. Therefore, when carrying out engineering slope design in similar geological environments, the slope structure and material composition should be fully identified, and the influence of groundwater on the slope stability state should be emphasized. These results can provide a reference for similar slope reinforcement designs. [ABSTRACT FROM AUTHOR]

A recent study confirmed that thiolutin is effective in the treatment of nucleotide-binding domain-like receptor protein 3 (NLRP3)-related inflammatory diseases. Nevertheless, whether thiolutin (THL) is involved in the regulation of NLRP3 inflammasome in ischemic stroke is not known. The murine neuronal cell oxygen–glucose deprivation (OGD) model was first established, and then different concentrations (25 nM and 50 nM) of THL were administered for 48 h incubation, respectively. Subsequently, cell viability and toxicity, and the levels of intracellular inflammatory factors interleukin-1β (IL-1β), interleukin-18 (IL-18), oxidative stress factors superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA), and NLRP3 inflammasome activation-related proteins pro-caspase, caspase-1, apoptosis-associated speck like-protein (ASC) and NLRP3 were examined, respectively. We further established the mouse middle cerebral artery occlusion (MCAO) model to evaluate the therapeutic effects of THL on cerebral infarction like behaviors in mice and the preventive effects on NLRP3 inflammasome activation in vivo. Cell cytotoxic, and the levels of inflammatory factors and oxidative stress were conspicuously increased, and NLRP3 inflammasome was materially activated in the OGD-induced cell model and MCAO-established mouse model, which were partially countered by THL treatment. Besides, intraperitoneal injection of THL could prominently reduce the cerebral infarct volume and neuromotor deficit scores in MCAO mice. The present study confirmed that THL attenuated neuronal and cerebral inflammatory injury caused by OGD and MCAO models in mice through restraining NLRP3 inflammasome activation in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Chimeric antigen receptor (CAR) T cell therapy has demonstrated clinical success in treating haematologic malignancies but has not been effective against solid tumours thus far. Trop2 is a tumour-related antigen broadly overexpressed on a variety of tumours and has been reported as a promising target for pancreatic cancers. Our study aimed to determine whether CAR T cells designed with a fully human Trop2-specific single-chain fragment variable (scFv) can be used in the treatment of Trop2-positive pancreatic tumours. Methods: We designed Trop2-targeted chimeric antigen receptor engineered T cells with a novel human anti-Trop2 scFv (2F11) and then investigated the cytotoxicity, degranulation, and cytokine secretion profiles of the anti-Trop2 CAR T cells when they were exposed to Trop2 + cancer cells in vitro. We also studied the antitumour efficacy and toxicity of Trop2-specific CAR T cells in vivo using a BxPC-3 pancreatic xenograft model. Results: Trop2-targeted CAR T cells designed with 2F11 effectively killed Trop2-positive pancreatic cancer cells and produced high levels of cytotoxic cytokines in vitro. In addition, Trop2-targeted CAR T cells, which persistently circulate in vivo and efficiently infiltrate into tumour tissues, significantly blocked and even eliminated BxPC-3 pancreatic xenograft tumour growth without obvious deleterious effects observed after intravenous injection into NSG mice. Moreover, disease-free survival was efficiently prolonged. Conclusion: These results show that Trop2-targeted CAR T cells equipped with a fully human anti-Trop2 scFv could be a potential treatment strategy for pancreatic cancer and could be useful for clinical evaluation. [ABSTRACT FROM AUTHOR]

The aim of this study is to define compositions and bioactive substances in the mucus derived from the deep-sea snail Volutharpa ampullacea perryi. V. ampullacea perryi, the so-called "false abalone," is a popular inexpensive seafood along the northern coast of China. The mucus secreted by the pleopod gland of this animal has always been considered a waste product. Here, we used traditional biochemical methods, MTT assays, and metabolomics analyses to determine the composition of the mucus and explore its potential value as a source of bioactive molecules. Crude protein was the major nutrient contained in the mucus of V. ampullacea perryi, and these proteins had anti-cancer potential. In addition, we identified and annotated 332 metabolites in the mucus. Of these, 61.75% had pharmacological functions, 3.61% could be used as cosmetics additives, and 9.04% had nutritional value. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management. [ABSTRACT FROM AUTHOR]

Nickel oxide/multi-walled carbon nanotube (NiO/MWCNT) composites were fabricated via a vacuum solution infiltration method combined with a calcination treatment. The crystalline structure and morphology were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) with selected area electron diffraction (SAED). The specific surface area, pore size, and pore volume were obtained by Brunauer-Emmett-Teller (BET). The as-prepared NiO/MWCNT composites deliver an initial discharge capacity of 1,015 mAh g with 86 % capacity retention (873 mAh g) after 50 cycles at a current rate of 0.1 C. The enhanced electrochemical performance is ascribed to the nanosized NiO and MWCNTs which can act as buffering matrix to relax the volume expansion and electron transfer conductor in the composites. [ABSTRACT FROM AUTHOR]

Cerebrovascular dysfunction is an early pathogenic event in Alzheimer's disease (AD) and plays a key role in the disease process. Cerebral hypoperfusion, brain glucose hypometabolism and disrupted blood-brain barrier (BBB) integrity contributed to the onset and progression of AD. However, the relationships between the age-related cognitive impairment and cerebral blood flow (CBF), energy metabolism and BBB have not been clearly explained. In this study, we investigated the cognitive function, CBF, BBB damage and expression level of glucose transporter (GLUT) 1 and 3 of senescence-accelerated mouse prone 8 (SAMP8), and the correlations between each of them were analyzed. When compared with SAMR1 (senescence-accelerated mouse resistant 1), the cognitive abilities of SAMP8 were damaged apparently even at 4 months of age, showing up a slower and more capricious acquisition in Morris water maze tasks. In both SAMP8 and SAMR1, reduced CBF and increased BBB leakage were observed with increasing age, but an earlier and more severe impairment was detected in SAMP8. In addition, alterations of GLUT1 and GLUT3 protein expression in cortex and hippocampus were more prominent in SAMP8. Correlation analysis demonstrated that the increased escape latency was correlated negatively with CBF and expression of glucose transporters; and positively with BBB permeability in the hippocampus. These results suggested that CBF, BBB integrity, the expression of GLUT1 and GLUT3 were significantly affected by age and strain, which were also closely associated with cognitive ability. The alteration in CBF and energy failure induced by aging and vascular insults resulted in cognitive decline in SAMP8. [ABSTRACT FROM AUTHOR]