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T‐cell‐mediated therapeutic strategies are the most potent effectors of cancer immunotherapy. However, an essential barrier to this therapy in solid tumors is disrupting the anti‐cancer immune response, cancer‐immunity cycle, T‐cell priming, trafficking and T‐cell cytotoxic capacity. Thus, reinforcing the anti‐cancer immune response is needed to improve the effectiveness of T‐cell‐mediated therapy. Tumor‐associated protease ADAM10, endothelial cells (ECs) and cytotoxic CD8+ T cells engage in complex communication via adhesion, transmigration and chemotactic mechanisms to facilitate an anti‐cancer immune response. The precise impact of ADAM10 on the intricate mechanisms underlying these interactions remains unclear. This paper broadly explores how ADAM10, through different routes, influences the efficacy of T‐cell‐mediated therapy. ADAM10 cleaves CD8+ T‐cell‐targeting genes and impacts their expression and specificity. In addition, ADAM10 mediates the interactions of adhesion molecules with T cells and influences CD8+ T‐cell activity and trafficking. Thus, understanding the role of ADAM10 in these events may lead to innovative strategies for advancing T‐cell‐mediated therapies. [ABSTRACT FROM AUTHOR]

Cold-stored Hami melon is susceptible to chilling injury, resulting in quality deterioration and reduced sales. Pre-storage treatment with chitosan reduces fruit softening and chilling injury in melon; however, the underlying mechanism remains unclear. In this study, Gold Queen Hami melons were treated with 1.5% chitosan solution for 10 min before cold storage at 3°C and then the effect of chitosan was examined on fruit firmness, weight loss, chilling injury, soluble solid content (SSC), pectin, and soluble sugar contents of melon fruit. Also, the enzyme activities and gene expressions related to fruit softening and starch and sucrose metabolism were investigated. Chitosan treatment reduced the fruit softening and chilling injury, maintained the high levels of starch and sucrose contents, and regulated the enzyme activities and gene expressions related to starch and sucrose metabolism. Fruit firmness was significantly positively correlated with sucrose and starch contents. Altogether, we uncovered the potential mechanism of chitosan coating mitigating melon softening and chilling injury through the regulation of starch and sucrose metabolism. [ABSTRACT FROM AUTHOR]

Purpose: Based on the transaction cost theory, this paper aims to investigate the impact of cultural distance on international strategic alliance formation and its underlying mechanisms. Design/methodology/approach: This paper uses the investment of foreign firms in the Chinese Venture Capital market as an empirical background, Obtaining VC data from Zero2IPO Private Equity, CVsource Investment Database (2001–2015). This paper chooses the Logit regression method, according to Lind's three-step method to test the inverted U-shaped relationship. Findings: The empirical analysis of foreign venture capital firms invested in China revealed that there is an inverted U-shaped relationship between cultural distance and the possibility of international strategic alliances. This relationship is the result of two opposing mechanisms, which are the need and the feasibility of international strategic alliances. In addition, this study further examined the moderating effects of social embeddedness and social reputation, revealing the boundary effects on the complex relationship between cultural distance and possible international strategic alliance formation. Originality/value: This study focuses on cultural difference, which is a key factor leading to a firm's transaction costs. Based on the transaction cost theory, this paper investigates the impact of cultural distance on international strategic alliance formation and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine Chan Su, has been shown to exert a potential for anticancer activity against various human cancer cell lines in vitro. However, no detailed studies have so far been reported on its action on human gallbladder carcinoma cells. In this study, bufalin remarkably inhibited growth in human gallbladder cancer cells by decreasing cell proliferation, inducing cell cycle arrest and apoptosis in a dose-dependent manner. Bufalin also disrupted the mitochondrial membrane potential (ΔΨm) and regulated the expression of cell cycle and apoptosis regulatory molecules. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that bufalin may be inducing mitochondria apoptosis pathways. Intraperitoneal injection of bufalin for 3 weeks significantly inhibited the growth of gallbladder carcinoma (GBC-SD) xenografts in athymic nude mice. Taken together, the results indicate that bufalin may be a potential agent for the treatment of gallbladder cancer. [ABSTRACT FROM AUTHOR]

Abstract  The dynamics of nitric oxide (NO) and peroxynitrite concentration changes during brain ischemia/reperfusion are poorly understood. In this paper, a NO-selective sensor was used to measure NO concentration changes in the rat brain hippocampus during global brain ischemia/reperfusion. Four-vessel occlusion model of transient global brain ischemia was used. Global cerebral ischemia was induced by occluding both common carotid arteries with artery nips (for 20 min) and reperfusion was induced by loosening the artery nips. Results showed that the changes of NO concentration during global brain ischemia/reperfusion could be divided into different stages. Together with the effects of O2 tension changes and NO synthase (NOS) on nitric oxide levels, we determined five stages in the NO concentration profile: (1) acute O2-limited decrease stage; (2) O2-limited steady stage; (3) neuronal NOS activation stage; (4) acute O2-recovery elevation stage; and (5) O2-recovery steady stage. In addition, a chemical reaction network model was constructed to simulate the dynamics of peroxynitrite during the reperfusion stage, and the effects of a change in the NO formation rate on the dynamics of peroxynitrite were investigated specifically. Results show the rate of NO formation has a great influence on peroxynitrite dynamics. [ABSTRACT FROM AUTHOR]

Background: Although many therapeutic strategies have been developed clinically, the mortality associated with acute respiratory distress syndrome remains very high. Objectives: In this research, we used a cytomechanical method to elucidate the reason for this. Methods: A549 cells were stimulated with lipopolysaccharide (LPS; 1 or 100 ng/ml) and/or mechanical stretch (5, 15, 30%) in varying frequency (0.2, 0.5, 1 Hz) at indicated time (1, 2, 4 h). Real time PCR and enzyme-linked immunosorbent assay were used to measure mRNA and protein levels of IL-8. Results: In the presence of mechanical stretch, 100 ng/ml LPS significantly increased IL-8 production after 4 h of 5% stretch (p < 0.05). In the presence of LPS, stretch enhanced LPS-induced IL-8 protein production in a force-, time- and frequency-dependent manner. At both the 1- and 4-hour time points, mechanical stretch and LPS increased IL-8 mRNA levels, respectively, and stretch enhanced LPS-induced IL-8 mRNA levels (p < 0.05). Conclusions: Using cytomechanic methods, we found a synergistic effect of LPS and mechanical stretch on IL-8 production. The response of alveolar type II cells to mechanical stretch depends on their different pathologic states and the applied mechanical stretch, which may reversely influence the outcome of patients with acute respiratory distress syndrome. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]