Study on the mechanical degradation characteristics and damage evolution of thermally damaged granite

The high geothermal environments encountered in deep mineral mining induce thermal damage to rocks, which can trigger geotechnical disasters in deep engineering projects. Therefore, exploring the degradation characteristics of rock mechanical properties and the damage evolution laws after high-temperature exposure is of significant importance for rock engineering in deep high-geothermal environments. By subjecting granite to the temperature range from ambient to 1200 ℃ and conducting macro-microscopic studies using optical microscopy, the degradation characteristics of Young's modulus and compressive strength in granite samples post various high-temperature treatments were investigated. Additionally, an analysis was performed on the internal cracks and damage evolution in thermally damaged granite from a microscopic perspective. The experimental results demonstrate that high-temperature treatments significantly reduce the mechanical properties of granite. The granite's compressive strength and Young's modulus decrease with increasing treatment temperatures, and the extent of crack development increases with temperature. The mechanic cal properties of granite are highly correlated with the development of internal crack structures. There is a power function relationship between the crack density and compressive strength in granite after different temperature treatments, indicating that crack density can effectively reflect the extent of thermal damage in granite

In Vitro/Vivo Activity of Potential MCR-1 Inhibitor in Combination With Colistin Againsts mcr-1-Positive Klebsiella pneumonia

Carbapenem resistance among strains of the nosocomial pathogen Klebsiella pneumoniae is increasing worldwide, causing serious clinical infections and higher mortality rates. Polymyxins are some of the few “last resort” options for treatment of carbapenem-resistant Enterobacteriaceae, including K. pneumoniae, however, the emergence of plasmid-mediated colistin resistance gene mcr-1 has largely rendered polymyxin-class antibiotics ineffective in a clinical setting. We previously identified a natural compound, pterostilbene, which has a synergistic effect in combination with polymyxins. Here, we aimed to determine whether pterostilbene application can restore the bactericidal activity of polymyxins against mcr-1-positive K. pneumoniae. Checkerboard MIC studies confirmed that pterostilbene reduces the MIC of colistin against mcr-1-positive clinical K. pneumoniae isolates, with the bacteria going from resistant to sensitive, and also demonstrated a synergistic effect with colistin (FIC index = 0.11 ± 0.04 or 0.28 ± 0.00). Time-killing assays showed that individually, both pterostilbene and colistin failed to eradicate K. pneumoniae strains, while in combination, the two drugs effectively eliminated K. pneumoniae ZJ02 and K. pneumoniae ZJ05 by 1–3 h post-inoculation. The combined disk test also showed increases in the zones of inhibition only for mcr-1-positive Escherichia coli and K. pneumoniae isolates. A mouse infection model demonstrated that the survival rate of mice at 7 days post-intraperitoneal injection with a lethal dose of K. pneumoniae ZJ05 was significantly promoted from 0 to 67% following combination therapy. This is the first time a MCR-1 inhibitor has successfully been used in combination with colistin against human clinical MCR-1 producing K. pneumoniae ZJ05 isolate

Triglyceride-inflammation score established on account of random survival forest for predicting survival in patients with nasopharyngeal carcinoma: a retrospective study

ObjectiveThis study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS.MethodsA retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration.ResultsThe C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration.ConclusionThe TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response

Application of toxicology data reliability assessment method, a toxicological data reliability evaluation tool, in the neurotoxic hazard assessment of glutamate acid and its salts

Objective This paper aims to evaluate data reliability of the neurotoxic hazard assessment of glutamate and its salts and provide recommendations, as well as to improve toxicology data reliability assessment method (TRAM) via trial application. Methods TRAM was used to evaluate the reliability of 60 articles which were selected by the method of systematic review documentation retrieval. The evaluation was based on types of toxicological data involved in each paper (laboratory animal data or human data) and they were scored by reliability criteria. The quality percentage was obtained via calculations to judge reliability categories and give recommendations. It’s necessary to note that the evaluation of each paper was independently completed by two persons in related fields. Results After three rounds of evaluation, the reliability of 12 articles were evaluated as "high" and recommended for priority use. The reliability of 43 articles was rated as "moderate" and can be used. The reliability of 5 articles was evaluated as "low" and not recommended to use. Conclusion TRAM takes both reporting quality and methodological quality into consideration, especially including human data reliability evaluation method which is absent in the other toxicology data reliability assessment tools. TRAM is more suitable for food safety risk assessment. It provides a better objective and scientific guarantee for hazard identification and risk assessment

TLR3 Regulated Poly I:C-Induced Neutrophil Extracellular Traps and Acute Lung Injury Partly Through p38 MAP Kinase

Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5