The poly(ADP-ribosyl)ation of BRD4 mediated by PARP1 promoted pathological cardiac hypertrophy

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy

Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy

Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes. Canonical autophagy requires all autophagy proteins (ATGs), whereas noncanonical autophagy is activated by diverse agents in which some of the essential autophagy proteins are dispensable. How noncanonical autophagy is induced and/or inhibited is still largely unclear. In this study, we demonstrated that AMDE-1, a recently identified chemical that can induce canonical autophagy, was able to elicit noncanonical autophagy that is independent of the ULK1 (unc-51-like kinase 1) complex and the Beclin1 complex. AMDE-1-induced noncanonical autophagy could be specifically suppressed by various V-ATPase (vacuolar-type H(+)-ATPase) inhibitors, but not by disturbance of the lysosome function or the intracellular ion redistribution. Similar findings were applicable to a diverse group of stimuli that can induce noncanonical autophagy in a FIP200-independent manner. AMDE-1-induced LC3 lipidation was colocalized with the Golgi complex, and was inhibited by the disturbance of Golgi complex. The integrity of the Golgi complex was also required for multiple other agents to stimulate noncanonical LC3 lipidation. These results suggest that the Golgi complex may serve as a membrane platform for noncanonical autophagy where V-ATPase is a key player. V-ATPase inhibitors could be useful tools for studying noncanonical autophagy

Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design

A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 µM respectively for PDE9 and PDE5, and about three orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors

Room-Temperature Synthesis of Highly-Efficient Eu3+-Activated KGd2F7 Red-Emitting Nanoparticles for White Light-Emitting Diode

Luminescent materials with high thermal stability and quantum efficiency are extensively desired for indoor illumination. In this research, a series of Eu3+-activated KGd2F7 red-emitting nanoparticles were prepared at room temperature and their phase structure, morphology, luminescence properties, as well as thermal stability, have been studied in detail. Excited by 393 nm, the resultant nanoparticles emitted bright red emissions and its optimal status was realized when the Eu3+ content was 30 mol%, in which the concentration quenching mechanism was triggered by electric dipole–dipole interaction. Through theoretical analysis via the Judd–Ofelt theory, one knows that Eu3+ situates at the high symmetry sites in as-prepared nanoparticles. Moreover, the internal and extra quantum efficiencies of designed nanoparticles were dependent on Eu3+ content. Furthermore, the studied nanoparticles also had splendid thermal stability and the corresponding activation energy was 0.18 eV. Additionally, via employing the designed nanoparticles as red-emitting constituents, a warm white light-emitting diode (white-LED), which exhibits low correlated color temperature (4456 K), proper luminous efficiency (17.2 lm/W) and high color rendering index (88.3), was developed. Our findings illustrate that Eu3+-activated KGd2F7 nanoparticles with bright red emissions are able to be used to promote the performance of white-LED

Surface Passivation with Selected Phosphine Oxide Molecules for Efficient Pure‐Blue Mixed‐Halide Perovskite Quantum Dot Light‐Emitting Diodes

Abstract Passivation of defects in halide perovskite using phosphine oxide or alkyl‐phosphonate has recently obtained a few remarkable achievements. However, effective application of phosphine oxide or alky‐phosphonate in passivating perovskite quantum dots (QDs) are seldom reported due to solubility issue or difficulty of amount control. In this work, two bifunctional organic molecules containing phosphine oxide groups, 2,4,6‐Tris[3‐(diphenylphosphinyl)phenyl]‐1,3,5‐triazine (PO‐T2T) and 2,7‐bis(diphenylphosphoryl)‐9,9′‐spirobifluorene (SPPO13), are deposited on QDs films by thermal evaporation. The molecules, both as passivation agents as well as electron transporting materials, exhibit stark contrast in passivating QDs and in light‐emitting diodes (LEDs) performance. A competition between charge transfer and defect passivation between the QDs and the molecules is proposed. In film, electron transfer from the QDs to PO‐T2T dominates and quench the QDs, while the passivation effect of PO‐T2T on the QDs dominates in driving device and enhances luminance of the LEDs. In contrast, passivation effect of SPPO13 on the QDs dominates both in films and in LEDs. A maximum EQE of 2.67% is obtained for the pure‐blue LED based on SPPO13‐passivated QDs films. This work provides a guide on the selection of passivation agents based on phosphine oxide and a promising passivation method for high‐efficient perovskite QD LEDs

Fabrication of Highly Stable Cs3Cu2I5-in-Glass Composite for X-Ray Imaging by SPS Technique

International audienceThe development of all‐inorganic lead‐free Cs3Cu2I5 perovskite materials has garnered significant attention due to their non‐toxic nature and unique optoelectronic properties, particularly in the field of X‐ray detection. However, the stability of perovskites remains a major concern for their optical applications. In this study, a highly stable Cs3Cu2I5‐in‐glass composite (Cs3Cu2I5@Borosilicate) is fabricated by spark plasma sintering (SPS), a rapid and low‐temperature sintering process. The Cs3Cu2I5@Borosilicate composite exhibits strong photoluminescence even after prolonged immersion in various polar solvents, whereas Cs3Cu2I5 perovskite loses its photoluminescence within seconds. Moreover, the Cs3Cu2I5@Borosilicate composite demonstrates robust radio‐luminescence under X‐ray irradiation, and its potential as a scintillator material is validated through prototype X‐ray imaging with a high spatial resolution (≈7 lp mm−1). This innovative composite material holds immense potential for scintillation applications and represents a promising approach for encapsulating perovskites in a transparent amorphous medium

SnFe₂O₄/ZnIn₂S₄/PVDF piezophotocatalyst with improved photocatalytic hydrogen production by synergetic effects of heterojunction and piezoelectricity

The polarized electric field inside piezoelectric materials has been proven to be a promising technique to boost photogenerated charge separation. Herein, a novel flexible SnFe2O4/ZnIn2S4/polyvinylidene fluoride ((CH2CF2)n, PVDF) (P–SZ) film piezophotocatalyst was successfully synthesized by combining PVDF, an organic piezoelectric material, with a SnFe2O4/ZnIn2S4 (SFO/ZIS) type II heterojunction photocatalyst. The hydrogen evolution rate of SFO/ZIS heterojunction with a SFO content of 5% is about 846.79 μmol·h−1·g−1, which is 3.6 times that of pristine ZIS. Furthermore, after being combined with PVDF, the optimum hydrogen evolution rate of P–SZ is about 1652.7 μmol·h−1·g−1 in the presence of ultrasound, which exceeds that of 5% SFO/ZIS by an approximate factor of 2.0. Based on experimental results, the mechanism of the improved photocatalytic performance of P–SZ was proposed on the basis of the piezoelectric field in PVDF and the formed heterojunction between SFO and ZIS, which effectively boosted the separation of photoinduced charges. This work provides an efficient strategy for multi-path collection and utilization of natural solar and vibrational energy to enhance photoactivity.</p