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Deciphering the crosstalk between metabolic reprogramming and epigenetic regulation is a promising strategy for cancer therapy. In this study, we discovered that the gluconeogenic enzyme PCK1 fueled the generation of S-adenosylmethionine (SAM) through the serine synthesis pathway. The methyltransferase SUV39H1 catalyzed SAM, which served as a methyl donor to support H3K9me3 modification, leading to the suppression of the oncogene S100A11. Mechanistically, PCK1 deficiency- induced oncogenic activation of S100A11 was due to its interaction with AKT1, which upregulated PI3K/AKT signaling. Intriguingly, the progression of hepatocellular carcinoma (HCC) driven by PCK1 deficiency was suppressed by SAM supplement or S100A11 KO in vivo and in vitro. These findings reveal the availability of the key metabolite SAM as a bridge connecting the gluconeogenic enzyme PCK1 and H3K9 trimethylation in attenuating HCC progression, thus suggesting a potential therapeutic strategy against HCC., Introduction Altered epigenetics and aberrant gene expression patterns are the major features of cancer (1). Dysregulated posttranslational modifications of histones, such as methylation and acetylation, are believed to play important [...]

Recently, the Qinghai–Tibetan Plateau has experienced significant warming. Climate warming is expected to have profound effects on plant community productivity and composition, which can drive ecosystem structure and function. To explore effects of warming on plant community productivity and composition, we conducted a warming experiment using open top chambers (OTCs) from 2012 to 2014 in alpine meadow and alpine steppe habitat on the central Qinghai–Tibetan Plateau. We measured aboveground net primary productivity (ANPP), community composition and species diversity under ambient and two levels of artificially warmed conditions across three years. Our results showed that warming significantly stimulated plant growth in the alpine meadow, but reduced growth on the alpine steppe. The increase of ANPP in alpine meadow was a result of an increase of plant height under warming. Warming-induced drought conditions were primarily responsible for the observed decrease of ANPP in an alpine steppe. Plant community composition and species diversity were not influenced by warming in alpine meadow. Alternatively, in alpine steppe, cover of graminoids and forbs significantly declined while legumes substantially increased under warming, subsequently resulting in rapid species losses. Changes in soil moisture were responsible for observed changes in graminoids and legumes in the alpine steppe. Overall, experimental results demonstrated that warming had a positive impact on plant community structure and function in alpine meadow and had a negative impact on these characteristics in an alpine steppe. This work highlights the important role of soil moisture for regulating plant productivity and community composition response to warming in the alpine steppe. In particular, the deep-rooted, drought resistant plants may increase in a warmer future in the central Qinghai–Tibetan Plateau. These changes may reduce habitat quality for the local community of grazers because many of the species that increased are also unpalatable to grazers.

Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2-71.2% during 1982-2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms.

Since 2000, the phenology has advanced in some years and at some locations on the Qinghai-Tibetan Plateau, whereas it has been delayed in others. To understand the variations in spring vegetation growth in response to climate, we conducted both regional and experimental studies on the central Qinghai-Tibetan Plateau. We used the normalized difference vegetation index to identify correlations between climate and phenological greening, and found that greening correlated negatively with winter-spring time precipitation, but not with temperature. We used open top chambers to induce warming in an alpine meadow ecosystem from 2012 to 2014. Our results showed that in the early growing season, plant growth (represented by the net ecosystem CO2 exchange, NEE) was lower in the warmed plots than in the control plots. Late-season plant growth increased with warming relative to that under control conditions. These data suggest that the response of plant growth to warming is complex and non-intuitive in this system. Our results are consistent with the hypothesis that moisture limitation increases in early spring as temperature increases. The effects of moisture limitation on plant growth with increasing temperatures will have important ramifications for grazers in this system.

Open, Grass- and Forb-Dominated (OGFD) ecosystems, including tundra, tropical grasslands and savanna, provide habitat for both wild and domesticated large ungulate herbivores. These ecosystems exist across a wide temperature gradient from the Arctic regions to the Equator, but are confined to a narrow set of moisture conditions that range from arid deserts to forest-dominated systems. Primary productivity in OGFD ecosystems appears extremely sensitive to environmental change. We compared global trends in the annual maximum and mean values of the Normalized Difference Vegetation Index (NDVI) and identified the key bioclimatic indices that controlled OGFD productivity changes in various regions for the period from 1982 to 2011. We found significantly increased or decreased annual maximum NDVI values of 36.3% and 4.6% for OGFD ecosystems, respectively. Trends in the annual mean NDVI are similar for most OGFD ecosystems and show greater area decreases and smaller area increases than trends in the annual maximum NDVI in global OGFD ecosystems during the study period. Ecosystems in which the productivity significantly increased were distributed mainly in the Arctic, mid-eastern South America, central Africa, central Eurasia and Oceania, while those with decreasing trends in productivity were mainly on the Mongolian Plateau. Temperature increases tended to improve productivity in colder OGFD ecosystems; and precipitation is positively correlated with productivity changes in grassland and savannas, but negatively correlated with changes in the Arctic tundra. Simple bioclimatic indices explain 42% to 55% of productivity changes in OGFD systems worldwide, and the main climatic predictors of productivity differed significantly between regions. In light of future climate change, the findings of this study will help support management of global OGFD ecosystems.

Although cancer cells are frequently faced with a nutrient- and oxygen-poor microenvironment, elevated hexosaminebiosynthesis pathway (HBP) activity and protein O-GlcNAcylation (a nutrient sensor) contribute to rapid growth of tumor and are emerging hallmarks of cancer. Inhibiting O-GlcNAcylation could be a promising anticancer strategy. The gluconeogenic enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) is downregulated in hepatocellular carcinoma (HCC). However, little is known about the potential role of PCK1 in enhanced HBP activity and HCC carcinogenesis under glucose-limited conditions. In this study, PCK1 knockout markedly enhanced the global O-GlcNAcylation levels under low-glucose conditions. Mechanistically, metabolic reprogramming in PCK1-loss hepatoma cells led to oxaloacetate accumulation and increased de novo uridine triphosphate synthesis contributing to uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis. Meanwhile, deletion of PCK1 also resulted in AMPK-GFAT1 axis inactivation, promoting UDP-GlcNAc synthesis for elevated OGlcNAcylation. Notably, lower expression of PCK1 promoted CHK2 threonine 378 O-GlcNAcylation, counteracting its stability and dimer formation, increasing CHK2-dependent Rb phosphorylation and HCC cell proliferation. Moreover, aminooxyacetic acid hemihydrochloride and 6-diazo-5-oxo-L-norleucine blocked HBP-mediated O-GlcNAcylation and suppressed tumor progression in liver-specific Pck1-knockout mice. We reveal a link between PCK1 depletion and hyper-O-GlcNAcylation that underlies HCC oncogenesis and suggest therapeutic targets for HCC that act by inhibiting O-GlcNAcylation., Introduction Gaining insight into the fundamental role of metabolic reprogramming in cancer has contributed immensely to our understanding of tumorigenesis and cancer progression (1). Nutrient limitations (such as glucose deprivation) [...]

Grassland cover is strongly influenced by climate change. The response of grassland cover to climate change becomes complex with background climate. There have been some advances in research on the sensitivity of grassland vegetation to climate change around the world, but the differences in climate sensitivity among grassland types are still unclear in alpine grassland. Therefore, we applied MODIS NDVI data and trend analysis methods to quantify the spatial and temporal variation of grassland vegetation cover on the Qinghai-Tibet Plateau. Then, we used multiple regression models to analyze the sensitivity of fractional vegetation cover (FVC) to climatic factors (Temperature, Precipitation, Solar radiation, Palmer drought severity index) and summarized the potential mechanisms of vegetation sensitivity to different climatic gradients. Our results showed (1) a significant increasing trend in alpine desert FVC from 2000–2018 (1.12 × 10−3/a, R2 = 0.56, p < 0.001) but no significant trend in other grassland types. (2) FVC sensitivity to climatic factors varied among grassland types, especially in the alpine desert, which had over 60% of the area with positive sensitivity to temperature, precipitation and PDSI. (3) The sensitivity of grassland FVC to heat factors decreases with rising ambient temperature while the sensitivity to moisture increases. Similarly, the sensitivity to moisture decreases while the sensitivity to thermal factors increases along the moisture gradient. Furthermore, the results suggest that future climate warming will promote grassland in cold and wet areas of the Qinghai-Tibet Plateau and may suppress vegetation in warmer areas. In contrast, the response of the alpine desert to future climate is more stable. Studying the impact of climate variation at a regional scale could enhance the adaptability of vegetation in future global climates. [ABSTRACT FROM AUTHOR]

Climate change is an important issue that affects both global warming and precipitation, and the main cause is increased N2O emissions. Temperature and moisture are key factors in grassland ecosystem's response to climate change, and they can affect N2O fluxes. To clarify the impacts of warming and precipitation changes on N2O fluxes, an experiment was conducted in a semiarid steppe in Inner Mongolia, China over a nine‐year period (2011–2019). Plant productivity and soil nutrient dynamics were examined concurrently from 2017 to 2019, and N2O fluxes were monitored in response to different treatment conditions: control (C), warming (W), precipitation addition (P), and warming and precipitation addition (WP). The results showed that N2O emissions in the growing season were higher than those in the nongrowing season. Warming and precipitation addition had no significant effect on N2O fluxes compared with ambient conditions. Compared with P treatment, warming increased N2O flux in nongrowing season and decreased it in growing season. N2O flux was positively correlated with soil temperature and moisture (p < 0.05). Warming had a significant positive effect on soil NH4+‐N, whereas additional precipitation had a large positive effect on soil total nitrogen and soil nitrate nitrogen. With the WP treatment, soil microbial biomass nitrogen (MBN) and soil microbial biomass carbon (MBC) increased by 53.8% and 41.9%, respectively. The decrease in N2O emissions during the growing season in the W treatment compared with the P treatment may be largely attributed to the greater dominance of Leymus chinensis. The results highlight that changes in species dominance play an important role in regulating N2O emissions, and that the N2O fluxes in the nongrowing season account for a large proportion of the changes in N2O fluxes. Therefore, The warming effects on N2O emissions during nongrowing seasons should be further investigated. [ABSTRACT FROM AUTHOR]