Metabolism and gene expression, which are two fundamental biological processes that are essential to all living organisms, reciprocally regulate each other to maintain homeostasis and regulate cell ...growth, survival and differentiation. Metabolism feeds into the regulation of gene expression via metabolic enzymes and metabolites, which can modulate chromatin directly or indirectly - through regulation of the activity of chromatin trans-acting proteins, including histone-modifying enzymes, chromatin-remodelling complexes and transcription regulators. Deregulation of these metabolic activities has been implicated in human diseases, prominently including cancer.
White light‐emitting diodes (WLEDs) are promising next‐generation solid‐state light sources. However, the commercialization route for WLED production suffers from challenges in terms of insufficient ...color‐rendering index (CRI), color instability, and incorporation of rare‐earth elements. Herein, a new two‐component strategy is developed by assembling two broadband emissive materials with self‐trapped excitons (STEs) for high CRI and stable WLEDs. The strategy addresses effectively the challenging issues facing current WLEDs. Based on first‐principles thermodynamic calculations, copper‐based ternary halides composites, CsCu2I3@Cs3Cu2I5, are synthesized by a facile one‐step solution approach. The composites exhibit an ideal white‐light emission with a cold/warm white‐light tuning and a robust stability against heat, ultraviolet light, and environmental oxygen/moisture. A series of cold/warm tunable WLEDs is demonstrated with a maximum luminance of 145 cd m−2 and an external quantum efficiency of 0.15%, and a record high CRI of 91.6 is achieved, which is the highest value for lead‐free WLEDs. Importantly, the fabricated device demonstrates an excellent operation stability in a continuous current mode, exhibiting a long half‐lifetime of 238.5 min. The results promise the use of the hybrids of STEs‐derived broadband emissive materials for high‐performance WLEDs.
Stable and highly luminescent CsCu2I3@Cs3Cu2I5 composites are synthesized through a one‐step spin‐coating method. They exhibit white‐light emission through self‐trapped excitons, as well as cold/warm white‐light tuning. By using the composites as a white‐light emitter, electrically driven cold/warm tunable WLEDs with a record color‐rendering index of 91.6 are successfully demonstrated, and a long half‐lifetime of 238.5 min is achieved.
Abstract
Glucose transporter GLUT1 is a transmembrane protein responsible for the uptake of glucose into the cells of many tissues through facilitative diffusion. Plasma membrane (PM) localization is ...essential for glucose uptake by GLUT1. However, the mechanism underlying GLUT1 PM localization remains enigmatic. We find that GLUT1 is palmitoylated at Cys207, and S-palmitoylation is required for maintaining GLUT1 PM localization. Furthermore, we identify DHHC9 as the palmitoyl transferase responsible for this critical posttranslational modification. Knockout of DHHC9 or mutation of GLUT1 Cys207 to serine abrogates palmitoylation and PM distribution of GLUT1, and impairs glycolysis, cell proliferation, and glioblastoma (GBM) tumorigenesis. In addition, DHHC9 expression positively correlates with GLUT1 PM localization in GBM specimens and indicates a poor prognosis in GBM patients. These findings underscore that DHHC9-mediated GLUT1 S-palmitoylation is critical for glucose supply during GBM tumorigenesis.
This work presents a strategy of combining the concepts of localized surface plasmons (LSPs) and core/shell nanostructure configuration in a single perovskite light‐emitting diode (PeLED) to ...addresses simultaneously the emission efficiency and stability issues facing current PeLEDs' challenges. Wide bandgap n‐ZnO nanowires and p‐NiO are employed as the carrier injectors, and also the bottom/upper protection layers to construct coaxial core/shell heterostructured CsPbBr3 quantum dots LEDs. Through embedding plasmonic Au nanoparticles into the device and thickness optimization of the MgZnO spacer layer, an emission enhancement ratio of 1.55 is achieved. The best‐performing plasmonic PeLED reaches up a luminance of 10 206 cd m−2, an external quantum efficiency of ≈4.626%, and a current efficiency of 8.736 cd A−1. The underlying mechanisms for electroluminescence enhancement are associated with the increased spontaneous emission rate and improved internal quantum efficiency induced by exciton–LSP coupling. More importantly, the proposed PeLEDs, even without encapsulation, present a substantially improved operation stability against water and oxygen degradation (30‐day storage in air ambient, 85% humidity) compared with any previous reports. It is believed that the experimental results obtained will provide an effective strategy to enhance the performance of PeLEDs, which may push forward the application of such kind of LEDs.
Localized surface plasmon enhanced all‐inorganic perovskite quantum dot light‐emitting diodes are fabricated based on coaxial core/shell heterojunction architecture, and an emission enhancement ratio of 1.55 is achieved. The performance of the plasmonic devices is remarkable in terms of their high luminance (10 206 cd m−2), current efficiency (8.736 cd A−1), and external quantum efficiency (4.626%), as well as a substantially improved operation stability.
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 acts as a protein kinase in coordinating glycolysis and the tricarboxylic acid (TCA) cycle, which is instrumental in cancer metabolism and tumorigenesis.
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•ERK and PIN1 regulate mitochondrial translocation of PGK1•PGK1, acting as a protein kinase, phosphorylates and activates PDHK1•PGK1 suppresses ROS production and coordinates glycolysis and the TCA cycle•Mitochondrial PGK1 promotes tumor cell proliferation and brain tumorigenesis
PGK1 is a cytosolic glycolytic enzyme. Li et al. demonstrate that conditions such as hypoxia and oncogenic mutations that activate ERK signaling can induce mitochondrial translocation of PGK1. Mitochondrial PGK1, functioning as a protein kinase, phosphorylates and activates PDHK1 to suppress mitochondrial pyruvate metabolism and promotes the Warburg effect.
Many types of human tumour cells overexpress the dual-specificity phosphatase Cdc25A. Cdc25A dephosphorylates cyclin-dependent kinase and regulates the cell cycle, but other substrates of Cdc25A and ...their relevant cellular functions have yet to be identified. We demonstrate here that EGFR activation results in c-Src-mediated Cdc25A phosphorylation at Y59, which interacts with nuclear pyruvate kinase M2 (PKM2). Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent β-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop. Cdc25A-mediated PKM2 dephosphorylation promotes the Warburg effect, cell proliferation and brain tumorigenesis. In addition, we identify positive correlations among Cdc25A Y59 phosphorylation, Cdc25A and PKM2 in human glioblastoma specimens. Furthermore, levels of Cdc25A Y59 phosphorylation correlate with grades of glioma malignancy and prognosis. These findings reveal an instrumental function of Cdc25A in controlling cell metabolism, which is essential for EGFR-promoted tumorigenesis.
Tumor-specific pyruvate kinase M2 (PKM2) is essential for the Warburg effect. In addition to 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.
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► PKM2 binds to and phosphorylates H3-T11 ► PKM2-dependent H3-T11 phosphorylation is required for H3-K9 acetylation ► H3-T11 phosphorylation is required for gene expression and tumorigenesis ► H3-T11 phosphorylation levels correlate with glioma malignancy and prognosis.
A kinase best known as a regulator of glycolysis doubles as a histone kinase to promote oncogenic gene expression.
In situ Raman spectroscopy is a powerful technique for probing the structure and phase composition of the electrode materials that are undergoing charge-discharge process. Herein, the charge storage ...mechanism of as-prepared Ni(HCO3)2 nanomaterial is successfully studied by using the in situ Raman spectroscopy. The charge storage can be attributed to the deep oxidation of Ni2+ into Ni3+, and the irreversible phase transformation of γ-NiOOH into disordered β-Ni(OH)2 damages the crystal structure of Ni(HCO3)2, arousing the capacity loss of the electrode during the long-term cycling process. Under the guidance of the experimental investigations, a porous Ni(HCO3)2/reduced graphene oxide (rGO) nanocomposite is designed and synthesized, exhibiting ultrahigh specific capacity (846 C g−1) and excellent rate capability (618 C g−1 at 20 A g−1). When coupled with an negative electrode based on rGO, the resulting hybrid supercapacitor shows an ultrahigh energy density of 66 Wh kg−1 at power density of 1.9 kW kg−1 and good cycling stability. These findings provide important insight into the mechanism of charge storage, and scientific basis for design of high-performance energy storage materials.
A porous Ni(HCO3)2/rGO nanocomposite used as a positive electrode for hybrid supercapacitor delivers high energy density, superior rate capability and good cycling stability. The energy storage behavior and structural evolution of the Ni(HCO3)2 nanomaterial are carefully investigated using in situ Raman spectroscopy. Display omitted
•The Ni(HCO3)2/rGO nanocomposite was successfully prepared, demonstrating high capacity and excellent rate performance.•The energy storage mechanism of the Ni(HCO3)2 is investigated by using in situ Raman spectroscopy.•The hybrid supercapacitor demonstrates ultrafast energy storage capability.
Dietary fructose is primarily metabolized in the liver. Here we demonstrate that, compared with normal hepatocytes, hepatocellular carcinoma (HCC) cells markedly reduce the rate of fructose ...metabolism and the level of reactive oxygen species, as a result of a c-Myc-dependent and heterogeneous nuclear ribonucleoprotein (hnRNP) H1- and H2-mediated switch from expression of the high-activity fructokinase (KHK)-C to the low-activity KHK-A isoform. Importantly, KHK-A acts as a protein kinase, phosphorylating and activating phosphoribosyl pyrophosphate synthetase 1 (PRPS1) to promote pentose phosphate pathway-dependent de novo nucleic acid synthesis and HCC formation. Furthermore, c-Myc, hnRNPH1/2 and KHK-A expression levels and PRPS1 Thr225 phosphorylation levels correlate with each other in HCC specimens and are associated with poor prognosis for HCC. These findings reveal a pivotal mechanism underlying the distinct fructose metabolism between HCC cells and normal hepatocytes and highlight the instrumental role of KHK-A protein kinase activity in promoting de novo nucleic acid synthesis and HCC development.
Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain
. Mental influence on perception is largely assumed to occur ...locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway
, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.
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