For cancer cells to proliferate, a balance must be built between biomass-forming, glucose-metabolized intermediates and ATP production. How intrinsic glucose carbon flow regulates this balance remains unclear. Here we show that mitochondrial phosphoenolpyruvate carboxykinase (PCK2), the hub molecule linking tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis by conversion of mitochondrial oxaloacetate (OAA) to phosphoenolpyruvate, regulates glucose carbon flow direction in stem-like cells that repopulate tumors (tumor-repopulating cells (TRCs)). PCK2 downregulation accelerated biosynthesis and transportation of citrate from mitochondria to the cytosol, leading to cytosolic glucose carbon flow via OAA-malate-pyruvate and acetyl-CoA-fatty acid pathways in TRCs. On the other hand, downregulating PCK2 hindered fumarate carbon flows in TCA cycle, leading to attenuated oxidative phosphorylation. In pathological terms, PCK2 overexpression slowed TRC growth in vitro and impeded tumorigenesis in vivo. Overall, our work unveiled unexpected glucose carbon flows of TRCs in melanoma that have implications for targeting metabolic aspects of melanoma.

Disruptions have the possibility of causing severe wall damage to large tokamaks like ITER. The mitigation of disruption damage is essential to the safe operation of a large-scale tokamak. The shattered pellet injection (SPI) technique, which is regarded as the primary injection method for ITER, presents several advantages relative to massive gas injection, including more rapid particle delivery, higher total particle assimilation, and more centrally peaked particle deposition. A dedicated argon SPI system that focuses on disruption mitigation and runaway current dissipation has been designed for the Joint Texas Experimental Tokamak (J-TEXT). A refrigerator is used to form a single argon pellet at around 64 K. The pellet will be shaped with a 5 mm diameter and a 1.5-10 mm length. Helium gas at room temperature will be used as a propellant gas for pellet acceleration. The pellet can be injected with a speed of 150-300 m/s. The time interval between injection cycles is about 8 min. The pellet will be shattered at the edge of the plasma and then injected into the core of plasma. The first experiments of SPI fast shutdown and runaway current dissipation have been performed.

The avoidance and suppression of runaway electron (RE) generation during disruptions is of great importance for the safe operation of tokamaks. Massive gas injection is used to suppress the generation of REs, but the poor gas mixing efficiency and extremely high density required to suppress RE generation make the full RE suppression unreliable. The magnetic perturbations provide an alternative RE suppression during disruptions. The use of mode penetration induced by resonant magnetic perturbations (RMPs) to suppress RE generation has been investigated on the J-TEXT tokamak. For a sufficiently long mode penetration duration, robust runaway suppression has been reached during the disruptions. The m/n=2/1 mode RMP with high amplitude excites large magnetic islands inside the plasma and leads to the large-scale destruction of magnetic surfaces during disruptions, which results in RE loss and runaway-free disruptions. The critical island width required for runaway suppression is estimated to be larger than 0.16 as the minor radius. This value might be slightly underestimated because of the misalignment between the electron cyclotron emission diagnostic and the island O-point. NIMROD simulations are used to investigate the effect of magnetic islands on RE generation during disruption, showing that the large magnetic islands have the ability to enhance RE seed loss during disruptions. RMP can excite large magnetic islands in the target plasma without tearing mode and might be a way to prevent RE generation during disruptions.

Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8-mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation. Multiple molecules presented notable alteration and Mertk signaling was aberrantly activated in the hematopoietic cells in irf8 mutants. Transgenic mertk overexpression in Tg(coro1a:mertk) zebrafish recapitulated the myeloid neoplasia-like syndrome in irf8 mutants. Moreover, functional interference with Mertk, via morpholino knockdown or genetic disruption, attenuated the myeloid expansion phenotype caused by Irf8 deficiency. Therefore, Mertk signaling is a critical downstream player in the Irf8-mediated regulation of the progression of myeloid neoplasia. Our study extends the understanding of the mechanisms underlying leukemogenesis.

Experiments of disruption mitigation with massive gas injection have been conducted in J-TEXT tokamak with various impurities (He, Ne, Ar and He&Ar (90%:10%) mixtures) injection. A 17channels polarimeter-interferometer (POLARIS) has been used to analyze the evolution of the electron density profile during pre-TQ and TQ phases. Experiments show that both the impurity species and applied high voltage of the valve have an obvious influence on the impurities deposition location and electron density profile. Moreover, with the high spatial resolution of POLARIS, a rather accurate impurity mixing efficiency has been obtained. The results show that Ar, the high atomic number (high-Z) impurity, has high cooling efficiency and evident mitigation effects, but the mixing efficiency for Ar is only of order 5%-8%. As for the low-Z impurity, He has fast propagation velocity and can reach high mixing efficiency, which is found to be of order 20%-40%. The use of the mixtures of high-Z and low-Z impurities (He&Ar (90%:10%)) can combine the fast penetration of He and high cooling efficiency of Ar, and the mixing efficiency is up to the order 20%-40%, improving the disruption mitigation efficiency and time response of disruption mitigation system.