1656Abstract. Humans have grazed on the Qinghai-Tibetan Plateau (QTP) for many thousands of years. In recent decades, the intensity of grazing has increased and several new management strategies have been put into place to address the resulting changes in rangeland condition. Effective management of grazing activities in this region requires understanding the impact of livestock grazing across the diverse array of alpine grassland ecosystems present in the QTP, but recent studies have identified a number of critical uncertainties in the ecological science that underlies these management principles. To address these uncertainties, we carried out a synthesis analysis of the effect of livestock grazing on 26 indicators of ecosystem structure and function based on 61 studies from 88 independent research sites within the QTP. Our synthesis results indicate that livestock grazing exerts complex controls on ecosystem structure and function, which vary according to local landscape characteristics. We found that grazing contributes to greater plant species diversity (Shannon-Wiener index, Simpson dominance index, and Pielou evenness index significantly increased 0.18, 0.05, and 0.03, respectively, due to grazing), but decreased aboveground biomass (47.15%), soil organic carbon (12.41%), soil total nitrogen (12.75%), and microbial biomass carbon (9.42%). Further, ecosystem function is controlled by interactions between grazing and other landscape characteristics such as elevation and mean annual temperature. The management regime currently in place in the QTP, which involves complete exclusion of grazing in some areas, can have variable effects on grassland health. Therefore, the complexity of these responses is an indication that livestock and grassland management may benefit from a more nuanced management regime than is currently utilized in the QTP.

AimsTo evaluate the expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) and their clinical and prognostic significance in primary esophageal squamous cell carcinoma (ESCC).ResultsThe expression rate of PD-1 and PD-L1 in ESCC was 33.5% (117/349) and 41.4% (222/536), respectively. PD-L1 expression differed significantly by tumor location, grade, lymph node metastases, and disease stage (P < 0.05). Moreover, its expression was associated with the disease free survival (DFS). Patients with positive PD-L1 expression had reduced risk for disease relapse compared to those without PD-L1 expression (Hazard ratio [HR] = 0.75, 95% confidence interval [CI]: 0.56–1.00, P = 0.048). Kaplan-Meier curves showed the similar result, P = 0.047. However, there was no significant correlation between PD-1 expression and clinicopathological factors or outcome in ESCC (P > 0.05).MethodsThe expression of PD-1 and PD-L1 was assessed by immunohistochemistry on tissue microarrays from 536 primary ESCC who underwent surgery during January 2008 and April 2012 in Zhejiang Cancer Hospital. Chi-square test and Cox proportional hazards regression were employed to analyze the associations between their expressions and clinicopathological variables and survival.ConclusionsOur results suggested that PD-L1 could be a favorable indicator of prognosis in ESCC.

Extracellular vesicles (EVs) are excellent potential vectors for the delivery of therapeutic drugs. However, issues with biological safety and disease targeting substantially limit their clinical application. EVs from red blood cells (RBC‐EVs) are potential drug delivery vehicles because of their unique biological safety. Here, we demonstrated that EVs, including RBC‐EVs, show natural liver accumulation. Mechanistically, the liver environment induces macrophages to phagocytize RBC‐EVs in a C1q‐dependent manner. RBC‐EVs loaded with antisense oligonucleotides of microRNA‐155 showed macrophage‐dependent protective effects against acute liver failure (ALF) in a mouse model. These RBC‐EVs were also effective in treatment of ALF. Furthermore, compared to routine doses of doxorubicin and sorafenib (SRF), RBC‐EVs loaded with doxorubicin or SRF showed enhanced therapeutic effects on a murine model of orthotopic liver cancer through a mechanism dependent on macrophages. Importantly, drug‐loaded RBC‐EVs showed no systemic toxicity at therapeutically effective doses, whereas routine doses of doxorubicin and SRF showed obvious toxicity. Thus, drug‐loaded RBC‐EVs hold high potential for clinical applications in the treatment of liver disease therapy.

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