Temporal and Spatial Variation of Aboveground Biomass of Pinus densata and Its Drivers in Shangri-La, CHINA.

Understanding the drivers of forest aboveground biomass (AGB) is essential to further understanding the forest carbon cycle. In the upper Yangtze River region, where ecosystems are incredibly fragile, the driving factors that make AGB changes differ from other regions. This study aims to investigate AGB's spatial and temporal variation of Pinus densata in Shangri-La and decompose the direct and indirect effects of spatial attribute, climate, stand structure, and agricultural activity on AGB in Shangri-La to evaluate the degree of influence of each factor on AGB change. The continuous sample plots from National Forest Inventory (NFI) and Landsat time series were used to estimate the AGB in 1987, 1992, 1997, 2002, 2007, 2012, and 2017. The structural equation model (SEM) was used to analyze the different effects of the four factors on AGB based on five scales: entire, 1987-2002, 2007-2017, low population density, and high population density. The results are as follows: (1) The AGB of Pinus densata in Shangri-La decreased from 1987 to 2017, with the total amount falling from 9.52 million tons to 7.41 million tons, and the average AGB falling from 55.49 t/ha to 40.10 t/ha. (2) At different scales, stand structure and climate were the drivers that directly affect the AGB change. In contrast, the agricultural activity had a negative direct effect on the AGB change, and spatial attribute had a relatively small indirect effect on the AGB change. (3) Analyzing the SEM results at different scales, the change of the contribution of the agricultural activity indicates that human activity is the main negative driver of AGB change in Shangri-La, especially at the high population density region. In contrast, the change of the contribution of the stand structure and climate indicates that the loss of old trees has an important influence on the AGB change. Forest resources here and other ecologically fragile areas should be gradually restored by adhering to policies, such as strengthening forest protection, improving forest stand quality, and limiting agricultural production activities.

Inhibition of autophagy augments the anticancer activity of α-mangostin in chronic myeloid leukemia cells.

Natural products possessing anticancer activity have been extensively studied because of their low toxicity and potential effect. α-Mangostin, a component of Garcinia mangostana Linn, is a xanthone derivative shown to have antioxidant and antitumor properties. This study was carried out to investigate how to improve the anticancer effects of α-mangostin in chronic myeloid leukemia (CML) cell lines bearing wild-type BCR-ABL or BCR-ABL-T315I mutation. We showed that α-mangostin inhibited cell proliferation of K562, KBM5 and KBM5-T315I cells in both a time- and dose-dependent manner. Significantly, α-mangostin increased the number of apoptotic cells and induced DNA fragmentation compared to control cells. Moreover, α-mangostin selectively inhibited proliferation in primary CML cells, while showing limited lethality in normal hematopoietic progenitors. Additionally, α-mangostin induced not only apoptosis but also autophagy in CML cells. α-Mangostin dramatically increased the expression levels of LC-3II, an autophagosome marker in mammals, and the accumulation of autophagic vacuoles (AVs). Inhibition of autophagy by chloroquine enhanced α-mangostin-mediated cytotoxicity through increasing apoptosis. Taken together, our data suggest that targeting the autophagy pathway is a promising therapeutic strategy to enhance α-mangostin-induced apoptosis. Our study provides an approach for future studies to explore this combination for the treatment of CML.

Inhibition of mTOR pathway sensitizes acute myeloid leukemia cells to aurora inhibitors by suppression of glycolytic metabolism.

Aurora kinases are overexpressed in large numbers of tumors and considered as potential therapeutic targets. In this study, we found that the Aurora kinases inhibitors MK-0457 (MK) and ZM447439 (ZM) induced polyploidization in acute myeloid leukemia (AML) cell lines. The level of glycolytic metabolism was significantly increased in the polyploidy cells, which were sensitive to glycolysis inhibitor 2-deoxy-D-glucose (2DG), suggesting that polyploidy cells might be eliminated by metabolism deprivation. Indeed, inhibition of mTOR pathway by mTOR inhibitors (rapamycin and PP242) or 2DG promoted not only apoptosis but also autophagy in the polyploidy cells induced by Aurora inhibitors. Mechanically, PP242 or2DGdecreased the level of glucose uptake and lactate production in polyploidy cells as well as the expression of p62/SQSTM1. Moreover, knockdown of p62/SQSTM1 sensitized cells to the Aurora inhibitor whereas overexpression of p62/SQSTM1 reduced drug efficacy. Thus, our results revealed that inhibition of mTOR pathway decreased the glycolytic metabolism of the polyploidy cells, and increased the efficacy of Aurora kinases inhibitors, providing a novel approach of combination treatment in AML.