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Background: Glucuronic acid metabolism participates in cellular detoxification, extracellular matrix remodeling and cell adhesion and migration. Here, we aimed to explore the crosstalk between dysregulated glucuronic acid metabolism and crucial metastatic signalling in glutathione S‐transferase zeta 1 (GSTZ1)‐deficient hepatocellular carcinoma (HCC). Methods: Transwell, HCC xenograft and Gstz1−/‐ mouse models were used to examine the role of GSTZ1 in HCC metastasis. Non‐targeted and targeted metabolomics and global transcriptomic analyses were performed to screen significantly altered metabolic and signalling pathways in GSTZ1 overexpressing hepatoma cells. Further, RNA‐binding protein immunoprecipitation, Biotin‐RNA pull‐down, mRNA decay assays and luciferase reporter assays were used to explore the interaction between RNA and RNA‐binding proteins. Results: GSTZ1 was universally silenced in both human and murine HCC cells, and its deficiency contributed to HCC metastasis in vitro and in vivo. UDP‐glucose 6‐dehydrogenase (UGDH)‐mediated UDP‐glucuronic acid (UDP‐GlcUA) accumulation promoted hepatoma cell migration upon GSTZ1 loss. UDP‐GlcUA stabilized TGFβR1 mRNA by enhancing its binding to polypyrimidine tract binding protein 3, contributing to the activation of TGFβ/Smad signalling. UGDH or TGFβR1 blockade impaired HCC metastasis. In addition, UGDH up‐regulation and UDP‐GlcUA accumulation correlated with increased metastatic potential and decreased patient survival in GSTZ1‐deficient HCC. Conclusions: GSTZ1 deficiency and subsequent up‐regulation of the glucuronic acid metabolic pathway promotes HCC metastasis by increasing the stability of TGFβR1 mRNA and activating TGFβ/Smad signalling. UGDH and a key metabolite, UDP‐GlcUA, may serve as prognostic markers. Targeting UGDH might be a promising strategy for HCC therapy. [ABSTRACT FROM AUTHOR]

Questions: The impact of grazing on the phenology of alpine plants has not been deeply explored. In particular, how the phenology of all species in the alpine plant community is affected by grazing has seldom been monitored. Study Site: Qinghai‐Tibetan Plateau of China. Methods: A linear mixed model was used to explore the effect of grazing regimes (continuous grazing, grazing exclusion and rotational grazing), species, and individuals of species on phenological stages at the community level. One‐way ANOVA was used to examine the difference in phenological stage across different species under the same grazing regime and timing of the phenological stages of each species across different grazing regimes. Pearson correlation analysis was used to explore linkages between plant phenology and leaf traits, linkages between phenological stages, as well as their intervals across different species. Results: The green‐up and withering time of different species both exhibited various response patterns to grazing regimes. The flowering time of most species was delayed by grazing, whereas the fruiting time of most species remained stable across grazing regimes. There were significant linkages between phenological stages and leaf traits; for example fruiting time was negatively related to the ratio of leaf N content (LNC) to leaf P content (LPC) under all grazing regimes. The phenological stages themselves, and their intervals, showed close relations; for example fruiting time was positively related to withering time, and negatively related to its interval. The divergence was higher during the flowering time than during other phenological stages. The divergence of all phenological stages was highest under grazing exclusion. Conclusions: The shifts in flowering time were advantageous for these plants to adapt to grazing, as flowering time can regulate interspecific temporal patterns and maintain the stability of subsequent phenological stages. Among grazing regimes, grazing exclusion led to greatest divergence of phenological stages across species, which possibly creates potential reproductive gaps. In the alpine meadows of the Qinghai‐Tibetan Plateau, the flowering time of most species was delayed by grazing, but the fruiting time of most species remained stable. Fruiting time was negatively related to the ratio of leaf N content to leaf P content. Grazing exclusion led to the greatest divergence of phenological stages across species, which possibly creates potential reproductive gaps. [ABSTRACT FROM AUTHOR]

Phenology is an important indicator of plant responses to environmental changes and is closely correlated with biomass production. However, how changes in phenological events affect plant biomass production when exposed to changing temperature and precipitation remain unclear.We conducted a 4‐year manipulative experiment of warming and precipitation addition to explore phenology–biomass interactions under climate change in a dry alpine meadow on the central Qinghai–Tibetan Plateau from 2015 to 2018.In dry and warm years, warming delayed phenology and precipitation addition advanced them. Warming decreased the biomass of Kobresia pygmaea in 2018 and the biomass of Poa pratensis in 2015, 2017 and 2018. However, precipitation addition significantly increased the biomass of Poa pratensis and Potentilla multifida in most of the experimental years. Phenological changes regulated the responses of biomass to treatments. Specifically, delay of green up of P. pratensis and delay of withering of K. pygmaea induced by warming can increase biomass production, but it can be offset by the direct negative effects of warming on biomass.Synthesis. Here we show how warming‐induced drought tend to decrease the biomass production of graminoids and the negative effects of warming on the biomass of P. pratensis and K. pygmaea were partially offset by green up postponement and withering postponement respectively. Our results highlights phenology is a crucial regulator for biomass production under climate change. Hence, both direct and indirect effects of warming and precipitation addition on phenology and biomass cannot be ignored when predicting biomass responses to climate change. [ABSTRACT FROM AUTHOR]

Abstract: Climate is a driver of terrestrial ecosystem carbon exchange, which is an important product of ecosystem function. The Qinghai–Tibetan Plateau has recently been subjected to a marked increase in temperature as a consequence of global warming. To explore the effects of warming on carbon exchange in grassland ecosystems, we conducted a whole‐year warming experiment between 2012 and 2014 using open‐top chambers placed in an alpine meadow, an alpine steppe, and a cultivated grassland on the central Qinghai–Tibetan Plateau. We measured the gross primary productivity, net ecosystem CO2 exchange (NEE), ecosystem respiration, and soil respiration using a chamber‐based method during the growing season. The results show that after 3 years of warming, there was significant stimulation of carbon assimilation and emission in the alpine meadow, but both these processes declined in the alpine steppe and the cultivated grassland. Under warming conditions, the soil water content was more important in stimulating ecosystem carbon exchange in the meadow and cultivated grassland than was soil temperature. In the steppe, the soil temperature was negatively correlated with ecosystem carbon exchange. We found that the ambient soil water content was significantly correlated with the magnitude of warming‐induced change in NEE. Under high soil moisture condition, warming has a significant positive effect on NEE, while it has a negative effect under low soil moisture condition. Our results highlight that the NEE in steppe and cultivated grassland have negative responses to warming; after reclamation, the natural meadow would subject to loose more C in warmer condition. Therefore, under future warmer condition, the overextension of cultivated grassland should be avoided and scientific planning of cultivated grassland should be achieved. [ABSTRACT FROM AUTHOR]