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Abstract The deck-charge structure, also known as axially decoupled charge structure, has been widely applied in open-pit rock excavation to improve blasting performance. However, the relationships between blast-induced fragmentation and deck-charge structures remain not well understood. This paper aims to experimentally investigate the influences of deck ratio, deck position and deck material on blast-induced fragmentation. Concrete specimens with dimension of 400 × 400 × 200 mm3 were used for small-scale single-hole blasting experiments. The dynamic fracturing process under blast loading was recorded with a high-speed camera. Displacement and strain fields were analyzed employing a 3D digital image correlation (DIC) system, and the fragment size distribution (FSD) was quantified through ImageJ, an advanced image-processing tool. The borehole wall pressure (BWP) was monitored through the embedded PVDF gauges within the test specimens. The results indicate that during deck charge blasting, the host concrete undergoes three phases: crushing, further crushing and fracturing, and radial crack development. Fragmentation performance improves within an optimal air-deck ratio range, while excessive ratios lead to poorer fragmentation compared to fully coupled charge blasting. The center deck charge yields the superior fragmentation, followed by double-ends and top deck charges. Water-deck charge generates finer fragmentation than air deck and polyethylene (PE) deck charges. Expanded polystyrene (EPS) deck charge does not facilitate fragmentation but may reduce vibration and limit damage to the remaining rock mass. Based on experiment results, production blasts with fully coupled charge, center air-deck charge and center water-deck charge were performed in an open-pit mine. These field tests revealed that the proposed center deck charge blasting reduced median fragment size by at least 15%, with the center water-deck charge demonstrating superior fragmentation by maximizing explosive energy utilization for rock fracturing.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality; it ranks as the second most common cause of cancer deaths in China. Most HCC patients are first diagnosed at an advanced stage. In recent years, targeted therapy combined with immunotherapy has become the preferred regimen for systemic treatment of intermediate-advanced HCC, while targeted therapy combined with immunotherapy plus local treatment could further improve the efficacy in many clinical studies. To better guide the clinical treatment for effective and safe combination therapy, our interdisciplinary panel on the treatment of intermediate-advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, interventional radiologists, and traditional Chinese medicine physicians have formulated this consensus based on current clinical studies and clinical medication experience for reference. The consensus contained 15 recommendations, including the applicable population and management, local treatment selection, conversion strategy, treatment strategy after tumor progression and management of common adverse reactions.

Abstract Stemming is one of the main concerns in blast of rock engineering due to its impact on explosion energy consumption and rock excavation performance. In this study, blast-induced rock fragmentation under different stemming conditions is numerically studied using combined numerical modelling and image processing. After careful determination the parameters of constitutive material models, the developed numerical model in LS-DYNA is verified based on the blast testing results including rock fracturing and fragment size distribution (FSD). The calibrated constitutive models are then used to model the pressure variation and rock disintegration produced by blasting with different stemming structures. The size data of simulated rock fragmentation are obtained by image-processing the cut surfaces of the numerical model with the program ImageJ, and the blast-created rock FSD is characterized using a three-parameter generalized extreme value function. The effects of the combination of explosive, air/sand deck and stemming on blast-induced rock fragmentation are quantitatively analysed, considering various stemming modes, stemming lengths and air/sand deck lengths. The results show that the blast-created fragment size decreases with an increase in stemming length, a decreasing in air/sand deck length, replacement of top stemming (stemming at borehole collar with air deck) with bottom stemming (stemming directly contact explosive) and alteration of air deck to sand deck, while the FSD range exhibits the opposite tendency. Bottom stemming is recommended for practical blasting due to its efficiency in rock fragmentation and robustness with respect to stemming length.

Abstract Background Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study. Methods IL-1β and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1β levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry. Results Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH. Conclusions Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases. Graphical Abstract

Overbreak and underbreak are the crucial problems during the blasting excavation of underground tunnels owing to their effects on the construction costs and operational safety. A critical challenge facing overbreak and underbreak control is the difficulty in developing guidelines with respect to various and complex engineering conditions. In this study, a series of field measurements of overbreak and underbreak using the FocusS 150 laser scanner were performed in a deep roadway of the Kaiyang phosphate mine, China. The distribution and extent of the overbreak and underbreak surrounding the roadway contour were accurately analyzed in accordance with the collected point cloud data. Subsequently, a simplified three-dimensional model was established to simulate the blasting excavation of pre-stressed roadway using the explicit dynamic analysis code LS-DYNA. A comparison of numerical and measurement results revealed that the proposed model was a reliable tool to simulate the overbreak and underbreak induced by blasting excavation. Thereafter, the influences of uncontrollable geological factors such as in situ stress conditions and controllable blasting factors including contour hole spacing (S), charge concentration (β) and decoupled coefficient (ζ) as well as stemming were further numerically investigated. The simulation results indicated that the lateral pressure coefficient significantly affected the distribution pattern of the overbreak and underbreak, while the stress magnitude contributed to their extents. Moreover, a comparison of the simulation findings and the field measurement data indicated that the minimal extents of the overbreak and underbreak corresponding the optimal contour blasting results were obtained at S = 0.70 m, β = 0.9 kg/m and ζ = 2.5, respectively. Furthermore, the contour blastholes stemmed with sand created smaller damage to the periphery rock mass of roadway and enhanced the utilization efficiency of explosive energy. The research findings of this study provide important implications for similar blasting excavation projects.

IntroductionCD11c+CD8+ T cells are an unconventional CD8+ T cell subset that exerts antiviral activity in infectious diseases. However, its characteristics in hepatocellular carcinoma (HCC) have not been elucidated.MethodsTwenty-six patients with hepatitis B virus (HBV)-related HCC and 25 healthy controls (HC) were enrolled. The frequency and phenotype of CD11c+CD8+ T cells in peripheral blood and tumors in situ were detected by flow cytometry and immunohistochemistry.ResultsBoth the HCC group and HC group had similar frequency and phenotype characteristics of CD11c+CD8+ T cells in the periphery. CD11c+CD8+ T cells were mainly composed of effector T cells, most of which were CD45RA+CCR7-. Compared with CD11c-CD8+ T cells, CD11c+CD8+ T cells had a higher proportion of CD38 and HLA-DR double positive, and expressed high levels of granzyme-B (GB) and degranulation marker CD107a, and produced high levels of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ). However, the ability of degranulation and TNF-α production of CD11c+CD8+ T cells in patients with HCC were significantly lower than that in healthy controls. The GB expression level of peripheral CD11c+CD8+ T cells in patients with advanced stage of HCC was significantly lower than that in patients with early stage of HCC, and the GB expression level of liver-infiltrating CD11c+CD8+ T cells in tumor tissues was lower than that in non-tumor tissues. More importantly, the GB expression level of peripheral CD11c+CD8+ T cells was negatively correlated with tumor volume. ConclusionsThese findings indicate that CD11c+CD8+ T cells may have potential anti-tumor activity and that GB+CD11c+CD8+ T cells are associated with disease progression in patients with HBV-related HCC.

Introduction: CD11c+CD8+ T cells are an unconventional CD8+ T cell subset that exerts antiviral activity in infectious diseases. However, its characteristics in hepatocellular carcinoma (HCC) have not been elucidated. Methods: Twenty-six patients with hepatitis B virus (HBV)-related HCC and 25 healthy controls (HC) were enrolled. The frequency and phenotype of CD11c+CD8+ T cells in peripheral blood and tumors in situ were detected by flow cytometry and immunohistochemistry. Results: Both the HCC group and HC group had similar frequency and phenotype characteristics of CD11c+CD8+ T cells in the periphery. CD11c+CD8+ T cells were mainly composed of effector T cells, most of which were CD45RA+CCR7-. Compared with CD11c-CD8+ T cells, CD11c+CD8+ T cells had a higher proportion of CD38 and HLA-DR double positive, and expressed high levels of granzyme-B (GB) and degranulation marker CD107a, and produced high levels of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ). However, the ability of degranulation and TNF-a production of CD11c+CD8+ T cells in patients with HCC were significantly lower than that in healthy controls. The GB expression level of peripheral CD11c+CD8+ T cells in patients with advanced stage of HCC was significantly lower than that in patients with early stage of HCC, and the GB expression level of liver-infiltrating CD11c+CD8+ T cells in tumor tissues was lower than that in non-tumor tissues. More importantly, the GB expression level of peripheral CD11c+CD8+ T cells was negatively correlated with tumor volume. Conclusions: These findings indicate that CD11c+CD8+ T cells may have potential anti-tumor activity and that GB+CD11c+CD8+ T cells are associated with disease progression in patients with HBV-related HCC. [ABSTRACT FROM AUTHOR]