Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active) and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile) cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into “whole-body” contextual models that mimic in vivo conditions.

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Electrocatalytic nitrogen reduction to ammonia has attracted increasing attention as it is more energy-saving and eco-friendly. For this endeavor, the development of high-efficiency electrocatalysts with excellent selectivity and stability is indispensable to break up the stable covalent triple bond in nitrogen. In this study, we report monodisperse Cu clusters loaded on defective ZrO 2 nanofibers for nitrogen reduction under mild conditions. Such an electrocatalyst achieves an NH 3 yield rate of 12.13 μg h −1 mg cat.−1 and an optimal Faradaic efficiency of 13.4% at −0.6 V versus the reversible hydrogen electrode in 0.1 M Na 2 SO 4 . Density functional theory calculations reveal that the N 2 molecule was reduced to NH 3 at the Cu active site with an ideal overpotential. Meanwhile, the interaction between bonding and antibonding of the Cu−N bond promotes activation of N 2 and maintains a low desorption barrier.

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Taking listed companies of strategic emerging industries as the research subject, this paper uses KZ index to measure the degrees of financing constraints and financial intermediary as well as the stock market to represent the level of financial development. Then empirical models are constructed to analyse whether financial development can alleviate the financing constraints of R&D investment or not. Finally, the paper further investigates the interaction of financial development and firm characteristics (including firm size, ownership nature and establishment time) on the impact of R&D investment. The results show that the degree of financing constraint is negatively correlated with R&D investment. Both the development of financial intermediary and stock market play an important role in alleviating the R&D financing constraints, and the development of the stock market can better alleviate the R&D financing constraint. Moreover, the development of financial intermediary and stock market plays a heterogeneous role among enterprises of different size, nature and time of establishment. In order to achieve the 13th Five-year Plan target of strategic emerging industries in China, the government and enterprises need to work together to improve the financial development level and reduce information asymmetry, so as to expand the investment channels of R&D investment and improve their innovation capability and competitiveness.

After integrating external ecological and endogenous factors of the development of the industry, the paper builds a financing ecology index system, and analyses the financing ecology of strategic emerging industries in recent years. Then the paper further analyses the influence of external and internal financing ecology on financing efficiency. The results show that the financing ecology of the strategic emerging industries, external financing ecology in particular, is in the continuous improvement. The financing efficiency is significantly positively correlated with the macro-economy level and the internal financing ecology, and significantly negatively correlated with the role of government. There is a positive but non-significant correlation between financial development and financing efficiency, meanwhile a negative and non-significant correlation between credit environment and financing efficiency. The internal and external financing ecology can be replaced to some extent. Therefore, the strategic emerging industries should give full consideration to the synergistic optimization of the endogenous factors and external financing ecology so as to improve the financing efficiency.

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