Asparagine synthetase (ASNS) catalyses the ATP-dependent conversion of aspartate to asparagine. However, both the regulation and biological functions of asparagine in tumour cells remain largely unknown. Here, we report that p53 suppresses asparagine synthesis through the transcriptional downregulation of ASNS expression and disrupts asparagine-aspartate homeostasis, leading to lymphoma and colon tumour growth inhibition in vivo and in vitro. Moreover, the removal of asparagine from culture medium or the inhibition of ASNS impairs cell proliferation and induces p53/p21-dependent senescence and cell cycle arrest. Mechanistically, asparagine and aspartate regulate AMPK-mediated p53 activation by physically binding to LKB1 and oppositely modulating LKB1 activity. Thus, we found that p53 regulates asparagine metabolism and dictates cell survival by generating an auto-amplification loop via asparagine-aspartate-mediated LKB1-AMPK signalling. Our findings highlight a role for LKB1 in sensing asparagine and aspartate and connect asparagine metabolism to the cellular signalling transduction network that modulates cell survival.

Recent studies have revealed that the oxidative entosehosphate athway (PPP), malic enzyme (ME), and folate metabolism are the three major routes for generating cellular NADPH, a key cofactor involved in redox control and reductive biosynthesis. Many tumor cells exhibit altered NADPH metabolism to fuel their rapid proliferation. However, little is known about how NADPH metabolism is coordinated in tumor cells. Here we report that ME1 increases the PPP flux by forming physiological complexes with 6-phosphogluconate dehydrogenase (6PGD). We found that ME1 and 6PGD form a hetero-oligomer that increases the capability of 6PGD to bind its substrate 6-phosphogluconate. Through activating 6PGD, ME1 enhances NADPH generation, PPP flux, and tumor cell growth. Interestingly, although ME1 could bind either the dimer-defect mutant 6PGD (K294R) or the NADP-binding defect 6PGD mutants, only 6PGD (K294R) activity was induced by ME1. Thus, ME1/6PGD hetero-complexes may mimic the active oligomer form of 6PGD. Together, these findings uncover a direct cross-talk mechanism between ME1 and PPP, may reveal an alternative model for signaling transduction via protein conformational simulation, and pave the way for better understanding how metabolic pathways are coordinated in cancer.

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Reduction of water pollutant emissions and energy consumption is regarded as a key environmental objective for the pulp and paper industry. The paper develops a bottom-up model called the Industrial Water Pollutant Control and Technology Policy (IWPCTP) based on an industrial technology simulation system and multiconstraint technological optimization. Five policy scenarios covering the business as usual (BAU) scenario, the structural adjustment (SA) scenario, the cleaner technology promotion (CT) scenario, the end-treatment of pollutants (EOP) scenario, and the coupling measures (CM) scenario have been set to describe future policy measures related to the development of the pulp and paper industry from 2010-2020. The outcome of this study indicates that the energy saving amount under the CT scenario is the largest, while that under the SA scenario is the smallest. Under the CT scenario, savings by 2020 include 70 kt/year of chemical oxygen demand (COD) emission reductions and savings of 7443 kt of standard coal, 539.7 ton/year of ammonia nitrogen (NH4-N) emission reductions, and savings of 7444 kt of standard coal. Taking emission reductions, energy savings, and cost-benefit into consideration, cleaner technologies like highly efficient pulp washing, dry and wet feedstock preparation, and horizontal continuous cooking, medium and high consistency pulping and wood dry feedstock preparation are recommended.

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NASICON-type solid electrolytes with excellent stability in moisture are promising in all-solid-state batteries and redox flow batteries. However, NASIOCN LiZr2(PO4)3 (LZP), which is more stable with lithium metal than the commercial Li1.3Al0.3Ti1.7(PO4)3, exhibits a low Li-ion conductivity of 10−6 S cm−1 because the fast conducting rhombohedral phase only exists above 50 °C. In this paper, the high-ionic conductive rhombohedral phase is stabilized by Y3+ doping at room temperature, and the hot-pressing technique is employed to further improve the density of the pellet. The dense Li1.1Y0.1Zr1.9(PO4)3 pellet prepared by hot-pressing shows a high Li-ion conductivity of 9 × 10−5 S cm−1, which is two orders of magnitude higher than that of LiZr2(PO4)3. The in-situ formed Li3P layer on the surface of Li1.1Y0.1Zr1.9(PO4)3 after contact with the lithium metal increases the wettability of the pellet by the metallic lithium anode. Moreover, the Li1.1Y0.1Zr1.9(PO4)3 pellet shows a relatively small interfacial resistance in symmetric Li/Li and all-solid-state Li-metal cells, providing these cells a small overpotential and a long cycling life.

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