Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA increased the expression levels of lipidated form LC3B and potently stimulated the autophagic flux, suggesting that DHA induces both autophagy and apoptosis in cancer cells expressing mutant p53. DHA led to the generation of mitochondrial reactive oxygen species (ROS), as shown by the mitochondrial ROS-specific probe mitoSOX. Similarly, pretreatment with the antioxidant N-acetyl-cysteine (NAC) markedly inhibited both the autophagy and the apoptosis triggered by DHA, indicating that mitochondrial ROS mediate the cytotoxicity of DHA in mutant p53 cells. Further, DHA reduced the levels of phospho-Akt and phospho-mTOR in a concentration-dependent manner, while NAC almost completely blocked that effect. Collectively, these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA.

The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming.

DJ-1 is a Parkinson's disease-associated gene whose protein product has a protective role in cellular homeostasis by removing cytosolic reactive oxygen species and maintaining mitochondrial function. However, it is not clear how DJ-1 regulates mitochondrial function and why mitochondrial dysfunction is induced by DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic neuronal cells exhibit defective mitochondrial respiratory chain complex I activity. In the present article we investigated the role of DJ-1 in complex I formation by using blue native-polyacrylamide gel electrophoresis and 2-dimensional gel analysis to assess native complex status. On the basis of these experiments, we concluded that DJ-1 null cells have a defect in the assembly of complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show defective supercomplex formation. It is known that aberrant formation of the supercomplex impairs the flow of electrons through the channels between respiratory chain complexes, resulting in mitochondrial dysfunction. We took two approaches to study these mitochondrial defects. The first approach assessed the structural defect by using both confocal microscopy with MitoTracker staining and electron microscopy. The second approach assessed the functional defect by measuring ATP production, O2 consumption, and mitochondrial membrane potential. Finally, we showed that the assembly defect as well as the structural and functional abnormalities in DJ-1 null cells could be reversed by adenovirus-mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease.

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.

No abstract

We have investigated the possibility of fabricating quantum dot light‐emitting diodes (QLEDs) using inkjet printing technology, which is the most attractive method for the full‐color patterning of QLED displays. By controlling the quantum dot (QD) ink formulation and inkjet printing condition, we successfully patterned QLED pixels in the 60‐in ultrahigh definition TV format, which has a resolution of 73 pixels per inch. The inkjet‐printed QLEDs exhibited a maximum luminance of 2500 cd/m2. Although the performance of inkjet‐printed QLEDs is low compared with that of QLEDs fabricated using the spin‐coating process, our results clearly indicate that the inkjet printing technology is suitable for patterning QD emissive layers to realize high‐resolution, full‐color QLED displays.

A series of indolo[3,2-b]indole (IDID) derivatives are designed as a novel structural platform for thermally activated delayed fluorescence (TADF) emitters. Intramolecular charge transfer (ICT)-type molecules consisting of IDID donor (D) and various acceptor (A) moieties are synthesized and characterized in the protocol of the systematical structure-property correlation. IDID derivatives exhibit high efficiency, prompt fluorescence as well as TADF with emission ranges tuned by the chemical structure of the acceptor units. Interestingly, almost all of the IDID derivatives show an identical energy level of the lowest triplet excited state (T) attributed to the locally excited triplet state of the IDID backbone (LE), while that of their lowest singlet excited state (S) is largely tuned by varying the acceptor units. Thus, we demonstrate the underlying mechanism in terms of the molecular engineering. Among the compounds, Tria-phIDID and BP-phIDID generate efficient delayed fluorescence based on the small energy gap between the lowest singlet and triplet excited states (ΔE) and mediation of the LE state. Organic light-emitting diodes with these Tria-phIDID and BP-phIDID as a dopant in the emitting layer show highly efficient electroluminescence with maximum external quantum efficiencies of 20.8% and 13.9%, respectively.

Charge balance between electrons and holes, which are injected into the quantum dot (QD) emission layer (EML), is critical for realizing stable and efficient QD light‐emitting diodes (QLEDs). ZnO has been widely used as an electron‐transport layer (ETL) because of its superior performance compared to other metal oxides. However, nearly barrier‐free electron injection into the QD EML leads to spontaneous charge transfer and excess electron injection, resulting in reduced device performance. Here, to adjust electron–hole balance and thereby improve the lifetime and efficiency of QLEDs, we introduce an yttrium (Y)‐doped ZnO (YZO) ETL into QLEDs. The sol–gel processed YZO film, with a mobility that could be simply tuned by varying the Y concentration, provides enhanced charge‐transport balance by suppressing excess electron flow to the QD EML. Furthermore, YZO helps suppress QD charging and smooth the surface morphology. Applying the YZO ETL into the inverted‐structure QLED enables us to achieve color‐saturated red emission, an improved external quantum efficiency of up to 8.6%, and an eight times longer lifetime compared to the device with undoped ZnO. This result provides a simple method for enhancing the performance of QLEDs by easily controlling metal doping concentration in the sol–gel processed ZnO ETL.