SUMMARY Tumor-specific pyruvate kinase M2 (PKM2) is essential for the Warburg effect. Besides its well-established role in aerobic glycolysis, PKM2 directly regulates gene transcription. However, the mechanism underlying this nonmetabolic function of PKM2 remains elusive. We show here that PKM2 directly binds to histone H3 and phosphorylates histone H3 at T11 upon EGF receptor activation. This phosphorylation is required for the dissociation of HDAC3 from the CCND1 and MYC promoter regions and subsequent acetylation of histone H3 at K9. PKM2-dependent histone H3 modifications are instrumental in EGF-induced expression of cyclin D1 and c-Myc, tumor cell proliferation, cell cycle progression, and brain tumorigenesis. In addition, levels of histone H3 T11 phosphorylation correlate with nuclear PKM2 expression levels, glioma malignancy grades, and prognosis. These findings highlight the role of PKM2 as a protein kinase in its nonmetabolic functions of histone modification, which is essential for its epigenetic regulation of gene expression and tumorigenesis.

SUMMARY It is unclear how the Warburg effect that exemplifies enhanced glycolysis in the cytosol is coordinated with suppressed mitochondrial pyruvate metabolism. We demonstrate here that hypoxia, EGFR activation, and expression of K-Ras G12V and B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1 (PGK1); this is mediated by ERK-dependent PGK1 S203 phosphorylation and subsequent PIN1-mediated cis–trans isomerization. Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338, which activates PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex. This reduces mitochondrial pyruvate utilization, suppresses reactive oxygen species production, increases lactate production, and promotes brain tumorigenesis. Furthermore, PGK1 S203 and PDHK1 T338 phosphorylation levels correlate with PDH S293 inactivating phosphorylation levels and poor prognosis in glioblastoma patients. This work highlights that PGK1 act as a protein kinase in coordinating glycolysis and the TCA cycle, which is instrumental in cancer metabolism and tumorigenesis.

Perovskite light-emitting diodes (PeLEDs), because of its fundamental scientific importance and practical applications in the fields of low-cost light source or display applications, have drawn worldwide attention in recent years. However, PeLEDs available today suffer from a compromise in their emission efficiency and operation stability. In this study, we designed and fabricated a stacking all-inorganic multilayer structure by using inorganic perovskite CsPbBr quantum dots (QDs) as the emissive layer and inorganic n-type MgZnO and p-type MgNiO as the carrier injectors, respectively. Through energy band engineering of carrier injectors by Mg incorporation and their thickness optimization, PeLEDs with maximum luminance of 3809 cd/m, luminous efficiency of 2.25 cd/A, and external quantum efficiency of 2.39% have been realized, which are much better than most PeLEDs from CHNHPbBr films, and comparable with the highest results reported on CsPbBr QDs LEDs. More importantly, the unencapsulated PeLEDs in a continuous current mode demonstrate a remarkable operation stability against water and oxygen degradation. After a continuous operation for 10 h under a dc bias (10.0 V), nearly 80% of the original efficiency of the PeLEDs has been retained, greatly superior to reference and other previously reported devices constructed with conventional organic carrier injectors. Our results obtained open possibilities for the design and development of high-efficiency and air-stable PeLEDs that are not dependent on expensive and less-stable organic carrier injectors.

SUMMARY Overcoming metabolic stress is a critical step in tumor growth. Acetyl-CoA generated from glucose and acetate uptake is important for histone acetylation and gene expression. However, how acetyl-CoA is produced under nutritional stress is unclear. We demonstrate here that glucose deprivation results in AMPK-mediated acetyl-CoA synthetase 2 (ACSS2) phosphorylation at S659, which exposed the nuclear localization signal of ACSS2 for importin α5 binding and nuclear translocation. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis. In addition, ACSS2 S659 phosphorylation positively correlates with AMPK activity in glioma specimens and grades of glioma malignancy. These results underscore the significance of nuclear ACSS2-mediated histone acetylation in maintaining cell homeostasis and tumor development.

Recently, a pressing requirement of solid-state lighting sources with high performance and low cost has motivated increasing research in metal halide perovskites. However, the relatively low emission efficiency and poor operation stability of perovskite light-emitting diodes (LEDs) are still critical drawbacks. In this study, a strategy of solution-processed all-inorganic heterostructure was proposed to overcome the emission efficiency and operation stability issues facing the challenges of perovskite LEDs. Solution-processed n-ZnO nanoparticles and p-NiO are used as the carrier injectors to fabricate all-inorganic heterostructured CsPbBr quantum dot LEDs, and a high-efficiency green emission is achieved with maximum luminance of 6093.2 cd/m, external quantum efficiency of 3.79%, and current efficiency of 7.96 cd/A. More importantly, the studied perovskite LEDs possess a good operation stability after a long test time in air ambient. Typically, the devices can endure a high humidity (75%, 12 h) and a high working temperature (393 K, three heating/cooling cycles) even without encapsulation, and the operation stability is better than any previous reports. It is anticipated that this work will provide an effective strategy for the fabrication of high-performance perovskite LEDs with good stability under ambient and harsh conditions, making practical applications of such LEDs a real possibility.