The Luoping Biota represents of the recovery of marine ecosystems after the Permian-Triassic Mass Extinction. To better understand the palaeoenvironmental background of the Luoping Biota, sedimentary analysis and multi-geochemical proxies (Mo, U, V, V/Cr, Mo EF , U EF , and V EF ) were assessed in Member II of the Middle Triassic Guanling Formation of the Xiangdongpo section in Luoping County, Yunnan Province. According to the facies characteristics and redox-sensitive elemental proxies, in combination with macrofossil and bioturbation evidence, five intervals (I, II, III, IV, and V) were recognized. The exceptional preservation of the fossils is related to two anoxic intervals (II and IV) sandwiched by three suboxic intervals (I, III, and V).Based on this study and regional correlation, it is concluded that anoxia in the watercolumn increased the preservation potential of macrofauna fossils and inhibited the survival of trace-making organisms. In addition, microbial mats could produce local anoxic and restricted micro-environments, preventing the disarticulation of the carcasses by water turbulence. Therefore, we demonstrate that anoxic conditions played a key role in the exceptional fossil preservation of the Luoping Biota.
The content and isotopic composition of pyrite sulfur are significantly affected by local depositional conditions and are sensitive to environmental evolution. Here, we use core QK11, collected from Xiapu Bay, southeast coast of China, to reveal how local depositional conditions constrained pyrite formation and sulfur isotopic composition since MIS5. Our results show that the content of pyrite sulfur is mainly controlled by the TOC content during interglacial intervals and is limited by the supplement of sulfate in glacial intervals. Therefore, the C/S ratios can effectively identify three transgressions since MIS5. The sulfur isotopic composition of pyrite ranges from -36.7 to 18.4‰ in the whole core. The occurrence of isotopically “heavy” pyrite is observed at the depth of 2.2~9.2, 27.2~33.8, and 43.5~62.5 mbsf, which is attributed to the influence of sulfate reservoir effect, depositional event, unsteady diagenetic environment, and other factors, highlighting the influence of local depositional and diagenetic processes on the isotopic composition of pyrite sulfur. Pyrite sulfur in other layers is generally depleted in 34S, as low as -36.7‰, indicating that the early-stage organiclastic sulfate reduction (OSR) plays an important role in sulfur isotopic fractionation. The results also suggest that organic carbon indicators (TOC/TN ratio and δ13C) combined with the C/S ratio can effectively distinguish between freshwater and marine environments, which is of great significance to reveal depositional evolution in deep time.
Summary
Glutamine metabolic reprogramming in acute myeloid leukaemia (AML) cells contributes to the decreased sensitivity to antileukemic drugs. Leukaemic cells, but not their myeloid counterparts, largely depend on glutamine. Glutamate dehydrogenase 1 (GDH1) is a regulation enzyme in glutaminolysis. However, its role in AML remains unknown. Here, we reported that GDH1 was highly expressed in AML: high GDH1 was one of the independent negative prognostic factors in AML cohort. The dependence of leukaemic cells on GDH1 was proved both in vitro and in vivo. High GDH1 promoted cell proliferation and reduced survival time of leukaemic mice. Targeting GDH1 eliminated the blast cells and delayed AML progression. Mechanistically, GDH1 knockdown inhibited glutamine uptake by downregulating SLC1A5. Moreover, GDH1 invalidation also inhibited SLC3A2 and abrogated the cystine‐glutamate antiporter system Xc−. The reduced cystine and glutamine disrupted the synthesis of glutathione (GSH) and led to the dysfunction of glutathione peroxidase‐4 (GPX4), which maintains the lipid peroxidation homeostasis by using GSH as a co‐factor. Collectively, triggering ferroptosis in AML cells in a GSH depletion manner, GDH1 inhibition was synthetically lethal with the chemotherapy drug cytarabine. Ferroptosis induced by inhibiting GDH1 provides an actionable therapeutic opportunity and a unique target for synthetic lethality to facilitate the elimination of malignant AML cells.
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