Chiral polymer hosts for circularly polarized electroluminescence devices

Polymer electroluminescence devices producing circularly polarized luminescence (CP PLEDs) have valuable photonic applications. The fabrication of a CP PLED requires a polymer host that provides the appropriate chiral environment around the emitting dopant. However, chemical strategies for the design of chiral polymer hosts remain underdeveloped. We have developed new polymer hosts for CP PLED applications. These polymers were prepared through a free-radical polymerization of 3-vinylcarbazole with a chiral N-alkyl unit. This chiral unit forces the carbazole repeat units to form mutually helical half-sandwich conformers with preferred (P)-helical sense along the polymer main chain. Electronic circular dichroism measurements demonstrate the occurrence of chirality transfer from chiral monomers to achiral monomers during chain growth. The (P)-helical-sense-enriched polymer interacts diastereoselectively with an enantiomeric pair of new phosphorescent (R)- and (S)-dopants. The magnitude of the Kuhn dissymmetry factor (g_abs) for the (P)-helically-enriched polymer film doped with the (R)-dopant was found to be one order of magnitude higher than that of the film doped with the (S)-dopant. Photoluminescence dissymmetry factors (g_PL) of the order of 10⁻³ were recorded for the doped films, but the magnitude of diastereomeric enhancement decreased to that of g_abs. The chiral polymer host permits faster energy transfer to the phosphorescent dopants than the achiral polymer host. Our photophysical and morphological investigations indicate that the acceleration in the chiral polymer host is due to its longer Förster radius and improved compatibility with the dopants. Finally, multilayer CP PLEDs were fabricated and evaluated. Devices based on the chiral polymer host with the (R)- and (S)-dopants exhibit electroluminescence dissymmetry factors (g_EL) of 1.09 × 10⁻⁴ and −1.02 × 10⁻⁴ at a wavelength of 540 nm, respectively. Although challenges remain in the development of polymer hosts for CP PLEDs, our research demonstrates that chiroptical performances can be amplified by using chiral polymer hosts.

Polymer electroluminescence devices producing circularly polarized luminescence (CP PLEDs) have valuable photonic applications.     

Effect of the Nanotube Radius and the Volume Fraction on the Mechanical Properties of Carbon Nanotube-Reinforced Aluminum Metal Matrix Composites

By using the advantages of carbon nanotubes (CNTs), such as their excellent mechanical properties and low density, CNT-reinforced metal matrix composites (MMCs) are expected to overcome the limitations of conventional metal materials, i.e., their high density and low ductility. To understand the behavior of composite materials, it is necessary to observe the behavior at the molecular level and to understand the effect of various factors, such as the radius and content of CNTs. Therefore, in this study, the effect of the CNT radius and content on the mechanical properties of CNT-Al composites was observed using a series of molecular dynamics simulations, particularly focusing on MMCs with a high CNT content and large CNT diameter. The mechanical properties, such as the strength and stiffness, were increased with an increasing CNT radius. As the CNT content increased, the strength and stiffness increased; however, the fracture strain was not affected. The behavior of double-walled carbon nanotubes (DWNTs) and single-walled carbon nanotubes (SWNTs) was compared through the decomposition of the stress–strain curve and observations of the atomic stress field. The fracture strain increased significantly for SWNT-Al as the tensile force was applied in the axial direction of the armchair CNTs. In the case of DWNTs, an early failure was initiated at the inner CNTs. In addition, the change in the elastic modulus according to the CNT content was predicted using the modified rule of mixture. This study is expected to be useful for the design and development of high-performance MMCs reinforced by CNTs.     

Optimized Aluminum Reflector for Enhancement of UVC Cathodoluminescence Based-AlGaN Materials with Carbon Nanotube Field Emitters

The far ultraviolet C (UVC) light sources based on carbon nanotube (CNT) field emitters as excitation sources have become promising light sources for sterilization, disinfection, and water purification. However, the low light extraction efficiency of UVC–CNT light sources still hinders the practical application of these structures. Herein, we report an optimized aluminum (Al) reflector to enhance the light extraction efficiency of UVC–CNT light sources. Optical analysis of UVC-CNT light sources covered by the Al reflectors with various thicknesses ranging from 30 to 150 nm was performed to realize the optimized reflector. The UVC-CNT light sources exhibit the highest light extraction efficiency when the Al reflector layer has an optimized thickness of 100 nm. For comparison, the cathodoluminescence (CL) spectra were recorded for UVC–CNT light sources with and without the optimized Al reflector. The measured light output power and the estimated power efficiency of the UVC–CNT light-source-tube with Al reflector were enhanced by about 27 times over the reference. This enhancement is mainly attributed to the outstanding reflection effect of the Al reflector.     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.     

Oat Extract Avenanthramide-C Reverses Hippocampal Long-Term Potentiation Decline in Tg2576 Mice

Memory deterioration in Alzheimer’s disease (AD) is thought to be underpinned by aberrant amyloid β (Aβ) accumulation, which contributes to synaptic plasticity impairment. Avenanthramide-C (Avn-C), a polyphenol compound found predominantly in oats, has a range of biological properties. Herein, we performed methanolic extraction of the Avns-rich fraction (Fr. 2) from germinated oats using column chromatography, and examined the effects of Avn-C on synaptic correlates of memory in a mouse model of AD. Avn-C was identified in Fr. 2 based on ¹H-NMR analysis. Electrophysiological recordings were performed to examine the effects of Avn-C on the hippocampal long-term potentiation (LTP) in a Tg2576 mouse model of AD. Avn-C from germinated oats restored impaired LTP in Tg2576 mouse hippocampal slices. Furthermore, Avn-C-facilitated LTP was associated with changes in the protein levels of phospho-glycogen synthase kinase-3β (p-GSK3β-S9) and cleaved caspase 3, which are involved in Aβ-induced synaptic impairment. Our findings suggest that the Avn-C extract from germinated oats may be beneficial for AD-related synaptic plasticity impairment and memory decline.     

Structural Requirements of 1-(2-Pyridinyl)-5-pyrazolones for Disproportionation of Boronic Acids

We observed an unusual formation of four-coordinate boron(III) complexes from the reaction of 1-(2-pyridinyl)-5-pyrazolone derivatives with arylboronic acids in the basic media. The exact mechanism is not clear; however, the use of unprotected boronic acid and the presence of a bidentate ligand appeared to be the key structural requirements for the transformation. The results suggest that base-promoted disproportionation of arylboronic acid with the assistance of the [N,O]-bidentate ligation of 1-(2-pyridinyl)-5-pyrazolone should take place and facilitate the formation of pyrazole diarylborinate. Experiments to obtain a deeper understanding of its mechanism are currently underway.     

Fermented Oyster Extract Attenuated Dexamethasone-Induced Muscle Atrophy by Decreasing Oxidative Stress

It is well known that oxidative stress induces muscle atrophy, which decreases with the activation of Nrf2/HO-1. Fermented oyster extracts (FO), rich in γ-aminobutyric acid (GABA) and lactate, have shown antioxidative effects. We evaluated whether FO decreased oxidative stress by upregulating Nrf2/HO-1 and whether it decreased NF-κB, leading to decreased IL-6 and TNF-α. Decreased oxidative stress led to the downregulation of Cbl-b ubiquitin ligase, which increased IGF-1 and decreased FoxO3, atrogin1, and Murf1, and eventually decreased muscle atrophy in dexamethasone (Dexa)-induced muscle atrophy animal model. For four weeks, mice were orally administered with FO, GABA, lactate, or GABA+Lactate, and then Dexa was subcutaneously injected for ten days. During Dexa injection period, FO, GABA, lactate, or GABA+Lactate were also administered, and grip strength test and muscle harvesting were performed on the day of the last Dexa injection. We compared the attenuation effect of FO with GABA, lactate, and GABA+lactate treatment. Nrf2 and HO-1 expressions were increased by Dexa but decreased by FO; SOD activity and glutathione levels were decreased by Dexa but increased by FO; NADPH oxidase activity was increased by Dexa but decreased by FO; NF-κB, IL-6, and TNF-α activities were increased by Dexa were decreased by FO; Cbl-b expression was increased by Dexa but restored by FO; IGF-1 expression was decreased by Dexa but increased by FO; FoxO3, Atrogin-1, and MuRF1 expressions were increased by Dexa but decreased by FO. The gastrocnemius thickness and weight were decreased by Dexa but increased by FO. The cross-sectional area of muscle fiber and grip strength were decreased by Dexa but increased by FO. In conclusion, FO decreased Dexa-induced oxidative stress through the upregulation of Nrf2/HO-1. Decreased oxidative stress led to decreased Cbl-b, FoxO3, atrogin1, and MuRF1, which attenuated muscle atrophy.     

Dianthiamides A–E,Proline-Containing Orbitides from Dianthus chinensis

Orbitides are plant-derived small cyclic peptides with a wide range of biological activities. Phytochemical investigation of the whole plants of Dianthus chinensis was performed with the aim to discover new bioactive orbitides. Five undescribed proline-containing orbitides, dianthiamides A–E (1–5), were isolated from a methanolic extract of Dianthus chinensis. Their structures were elucidated by extensive analysis of 1D and 2D NMR and HRESI–TOF–MS as well as ESI–MS/MS fragmentation data. The absolute configuration of the amino acid residues of compounds 1–5 was determined by Marfey’s method. All compounds were tested for their cytotoxic activity, and dianthiamide A (1) exhibited weak activity against A549 cell line with IC₅₀ value of 47.9 μM.     

Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.     

Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance

Homologous recombination (HR) repair deficiency impairs the proper maintenance of genomic stability, thus rendering cancer cells vulnerable to loss or inhibition of DNA repair proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1). Inhibitors of nuclear PARPs are effective therapeutics for a number of different types of cancers. Here we review key concepts and current progress on the therapeutic use of PARP inhibitors (PARPi). PARPi selectively induce synthetic lethality in cancer cells with homologous recombination deficiencies (HRDs), the most notable being cancer cells harboring mutations in the BRCA1 and BRCA2 genes. Recent clinical evidence, however, shows that PARPi can be effective as cancer therapeutics regardless of BRCA1/2 or HRD status, suggesting that a broader population of patients might benefit from PARPi therapy. Currently, four PARPi have been approved by the Food and Drug Administration (FDA) for the treatment of advanced ovarian and breast cancer with deleterious BRCA mutations. Although PARPi have been shown to improve progression-free survival, cancer cells inevitably develop resistance, which poses a significant obstacle to the prolonged use of PARP inhibitors. For example, somatic BRCA1/2 reversion mutations are often identified in patients with BRCA1/2-mutated cancers after treatment with platinum-based therapy, causing restoration of HR capacity and thus conferring PARPi resistance. Accordingly, PARPi have been studied in combination with other targeted therapies to overcome PARPi resistance, enhance PARPi efficacy, and sensitize tumors to PARP inhibition. Moreover, multiple clinical trials are now actively underway to evaluate novel combinations of PARPi with other anticancer therapies for the treatment of PARPi-resistant cancer. In this review, we highlight the mechanisms of action of PARP inhibitors with or without BRCA1/2 defects and provide an overview of the ongoing clinical trials of PARPi. We also review the current progress on PARPi-based combination strategies and PARP inhibitor resistance.Subject terms: Cancer therapy, Mechanisms of disease, PolyADP-ribosylation