Search

Epigenetic mechanisms are considered to contribute to diabetic nephropathy by maintaining memory of poor glycemic control during the early stages of diabetes. However, DNA methylation changes in the human kidney are poorly characterized, because of the lack of cell type-specific analysis. We examined DNA methylation in proximal tubules (PTs) purified from patients with diabetic nephropathy and identified differentially methylated CpG sites, given the critical role of proximal tubules in the kidney injury. Hypermethylation was observed at CpG sites annotated to genes responsible for proximal tubule functions, including gluconeogenesis, nicotinamide adenine dinucleotide synthesis, transporters of glucose, water, phosphate, and drugs, in diabetic kidneys, whereas genes involved in oxidative stress and the cytoskeleton exhibited demethylation. Methylation levels of CpG sites annotated to ACTN1, BCAR1, MYH9, UBE4B, AFMID, TRAF2, TXNIP, FOXO3, and HNF4A were correlated with the estimated glomerular filtration rate, whereas methylation of the CpG site in RUNX1 was associated with interstitial fibrosis and tubular atrophy. Hypermethylation of G6PC and HNF4A was accompanied by decreased expression in diabetic kidneys. Proximal tubule-specific hypomethylation of metabolic genes related to HNF4A observed in control kidneys was compromised in diabetic kidneys, suggesting a role for aberrant DNA methylation in the dedifferentiation process. Multiple genes with aberrant DNA methylation in diabetes overlapped genes with altered expressions in maladaptive proximal tubule cells, including transcription factors PPARA and RREB1. In conclusion, DNA methylation derangement in the proximal tubules of patients with diabetes may drive phenotypic changes, characterized by inflammatory and fibrotic features, along with impaired function in metabolism and transport. NEW & NOTEWORTHY: Cell type-specific DNA methylation patterns in the human kidney are not known. We examined DNA methylation in proximal tubules of patients with diabetic nephropathy and revealed that oxidative stress, cytoskeleton, and metabolism genes were aberrantly methylated. The results indicate that aberrant DNA methylation in proximal tubules underlies kidney dysfunction in diabetic nephropathy. Aberrant methylation could be a target for reversing memory of poor glycemic control. [ABSTRACT FROM AUTHOR]

Although Earth‐abundant, ubiquitous, metal‐based thermally activated delayed fluorescence (TADF) complexes are among the most promising candidate materials for next‐generation organic light‐emitting devices (OLEDs), few complexes are explored. Herein, a highly emissive aluminum(III)‐TADF complex—Al(MCzDBM)3—with three β‐diketone ligands is presented as a sensitizer for multiresonance (MR)‐TADF emitters. This complex exhibited green emission with suitable photophysical functions as a sensitizer, such as a high photoluminescent quantum yield (PLQY) of up to 97% with reduced aggregation‐caused quenching, a high radiative rate constant (kr) of 5.6 × 107 s−1, and a short delayed lifetime (τd) of 4.0 µs in the solid state. A solution‐processed Al(MCzDBM)3‐based OLED exhibited an external quantum efficiency (EQE) of 23.6%. This complex sensitized a yellow MR‐TADF emitter, yielding a near‐unity PLQY, and is used to fabricate a solution‐processed hyperfluorescent OLED with an EQE of 21.6% and full width at half maximum of 45 nm. [ABSTRACT FROM AUTHOR]

The horizontal orientation of the emissive transition dipole moment (TDM) of emissive molecules is a crucial factor in improving the efficiency of organic light‐emitting diodes (OLEDs). However, the mechanism of this horizontal orientation remains unclear. Herein, to elucidate the horizontal orientation mechanism of the TDM of the molecules in thermally activated delayed fluorescent (TADF) emitters, the relationship between the horizontal orientation ratio (Θ) of the TDM and the key parameters of stick‐like TADF emitters dispersed in carbazole‐based host materials is systematically and quantitatively investigated. The introduction of functional groups containing weak CH/n (n = O, N) hydrogen bonds into the host material is found to significantly increase the Θ values up to 30%. The physical parameters of the dispersed emitter exhibit a strong relationship with the Θ values, with the following influence order: glass transition temperature (Tg) ≥ total surface area of the largest π‐plane and the corresponding parallel π‐plane > molecular weight > aspect ratio > permanent dipole moment. The Tg value of the host material is another key parameter determining the Θ values. By using a P=O‐based host material, namely mCP2PO, a high PLQY of 97%, a high Θ value of 88%, and a sky‐blue OLED with an EQE of 37.6% are simultaneously realized. [ABSTRACT FROM AUTHOR]

Although λ5‐phosphinine derivatives are known as a promising class of blue fluorescent emitters, those photoluminescent quantum yield (PLQY) values have been reached up to 92 %, however, only a few examples have been explored as an emitter for blue organic light‐emitting device (OLED), and the external quantum efficiency (EQE) has been below 2.4 % so far. In this study, we newly developed two types of blue λ5‐phosphinine derivatives namely CN‐COCF3 and CO2Me‐CHO, and investigated the photophysical properties in the solid states. The photophysical analyses in solid state films suggested that the strong electron‐accepting nature of these λ5‐phosphinine derivatives caused the inferior PLQY values, and the exciplex formation with the host and neighboring materials should be avoided to improve the device efficiency. By choosing suitable host and neighboring materials with deep ionization potentials, we successfully realized efficient blue fluorescent OLEDs with EQE of over 4 % and CIE (0.14, 0.18). This is among the best in λ5‐phosphinine‐based blue OLEDs so far. [ABSTRACT FROM AUTHOR]

Realizing a perfectly horizontal orientation of the transition dipole moment (TDM) in an emitter molecule is one of the most promising approaches used to boost the efficiency of organic light-emitting devices (OLEDs). However, fundamental guidelines for horizontal orientation are still under discussion, and active control of the molecular orientation by a host material is rarely realized. In this study, we systematically investigated the structure–molecule orientation relationships of representative heteroleptic iridium complexes (HICs) in carbazole-based host materials to formulate guidelines for active control of the TDM. The horizontal orientation ratio (Θ) of the TDM is strongly correlated with (i) the glass transition temperature (Tg) of the host material and (ii) the surface area (SML) of the aromatic main ligand in the HICs. Furthermore, compared with emitters with the same SML values, the Θ values tended to increase when the contact area with the underlying layer increased. These results suggest that (i) the strength of the intermolecular interaction between the emitter and host material and (ii) the contact area of the main ligand in the emitter are crucial factors in the control of TDM in HICs. Finally, we successfully fabricated a yellow phosphorescent OLED with an external quantum efficiency of 29.0%. [ABSTRACT FROM AUTHOR]

Despite the promising photofunctionalities of β-diketone-based thermally activated delayed fluorescent (TADF) emitters, such as excited-state intramolecular proton transfer and the utilization of the ligand in the emissive metal complex, examples in the blue region are scarcely explored. To achieve a shorter wavelength emission, three variations of β-diketone/tetramethylcarbazole conjugated TADF emitters, designated as MCzX derivatives, were synthesized, and showed bluish-green-to green emission. Among these emitters, MCzDBM exhibited a photoluminescent quantum yield of 79% and a horizontal emission dipole orientation ratio of 88%, when incorporated into a phosphine-oxide-based host material, mCPPO. The consequent OLED has been evaluated to be highly efficient, with an external quantum efficiency of 24.6%. These performance parameters are the best among those reported thus far for β-diketone-based TADF emitters. [ABSTRACT FROM AUTHOR]

Although multi-resonance thermally activated delayed fluorescence (MR-TADF) emitters exhibit near-unity photoluminescence quantum yield (PLQY) and narrow-band emission, their aggregation-caused quenching (ACQ) and random molecular orientation in organic light-emitting devices (OLEDs) restrict the maximization of their full potential. In this study, we developed a series of novel phenylene-bridged MR-TADF emitters with varying numbers of carbazole units. These emitters exhibited sky-blue emission at approximately 480 nm with a near-unity PLQY, a small full width at half maximum of 26–31 nm, and horizontal molecular orientation of ∼ 80%. The chemical modifications with a phenylene bridge and varied carbazole units reduced the ACQ behavior at high concentration ratios and greatly enhanced the values from 62% to 80%. The corresponding OLED exhibited an external quantum efficiency of approximately 30%. [ABSTRACT FROM AUTHOR]

The periodontal ligament (PDL) is a fibrous connective tissue that attaches the tooth to the alveolar bone. We previously demonstrated the ability of PDL fibroblast-like cells to construct an endothelial cell (EC) marker-positive blood vessel-like structure, indicating the potential of fibroblastic lineage cells in PDL tissue as precursors of endothelial progenitor cells (EPCs) to facilitate the construction of a vascular system around damaged PDL tissue. A vascular regeneration around PDL tissue needs proliferation of vascular progenitor cells and the subsequent differentiation of the cells. Transforming growth factor-β (TGF-β) is known as an inducer of endothelial-mesenchymal transition (EndMT), however, it remains to be clarified what kinds of TGF-β signals affect growth and mesenchymal differentiation of PDL-derived EPC-like fibroblastic cells. Here, we demonstrated that TGF-β1 not only suppressed the proliferation of the PDL-derived EPC-like fibroblastic cells, but also induced smooth muscle cell (SMC) markers expression in the cells. On the other hand, TGF-β1 stimulation suppressed EC marker expression. Intriguingly, overexpression of Smad7, an inhibitor for TGF-β-induced Smad-dependent signaling, suppressed the TGF-β1-induced growth inhibition and SMC markers expression, but did not the TGF-β1-induced downregulation of EC marker expression. In contrast, p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 suppressed the TGF-β1-induced downregulation of EC marker expression. In addition, the TGF-β1-induced SMC markers expression of the PDL-derived cells was reversed upon stimulation with fibroblast growth factor (FGF), suggesting that the TGF-β1 might not induce terminal SMC differentiation of the EPC-like fibroblastic cells. Thus, TGF-β1 not only negatively controls the growth of PDL-derived EPC-like fibroblastic cells via a Smad-dependent manner but also positively controls the SMC-differentiation of the cells possibly at the early stage of the translineage commitment via Smad- and p38 MAPK-dependent manners.