Spin-Flip-Restricted Multiple-Resonance Emitters for Extended Device Lifetime in Indolocarbazole-Based Blue Organic Light-Emitting Diodes.

In this study, a multiple-resonance (MR) core structure is developed with a spin-flip-restricted emission mechanism based on a fused indolo[3,2,1-jk]carbazole (ICz) framework as emitters to improve the lifetime of blue organic light-emitting diodes. The molecular skeleton modulation approach applied to the conjugated π-system effectively stabilizes the triplet energy of the fused ICz emitters and narrows the full-width-at-half maximum (<20 nm). In addition, the emitters exhibit higher exciton stability than conventional boron-based MR emitters. The fused ICz-based blue fluorescent device exhibits a high external quantum efficiency of 7.2%, a blue index of 68.6 cd A-1 at a Commission internationale de l'éclairage y coordinate (CIEy) of 0.075, and a device lifetime 1.8 times longer than that of a boron-based emitter. In addition, a phosphor-sensitized fluorescent device based on the ICz emitter exhibited an improved external quantum efficiency of 20.6% with a CIEy coordinate of 0.076.

OR2H2 Activates CAMKKß-AMPK-Autophagy Signaling Axis and Suppresses Senescence in VK2/E6E7 Cells.

Olfactory receptors are expressed in multiple extra-nasal tissues and these ectopic olfactory receptors mediate tissue-specific functions and regulate cellular physiology. Ectopic olfactory receptors may play key roles in tissues constantly exposed to odorants, thus the functionality of these receptors in genital tissues is of particular interest. The functionality of ectopic olfactory receptors expressed in VK2/E6E7 human vaginal epithelial cells was investigated. OR2H2 was the most highly expressed olfactory receptor expressed in VK2/E6E7 cells, and activation of OR2H2 by aldehyde 13-13, a ligand of OR2H2, increased the intracellular calcium and cAMP concentrations. Immunoblotting demonstrated that activation of OR2H2 by aldehyde 13-13 stimulated the CAMKKß-AMPK-mTORC1-autophagy signaling axis, and that these effects were negated by OR2H2 knockdown. AMPK is known to regulate senescence; consequently, we investigated further the effect of aldehyde 13-13 on senescence. In H2O2-induced senescent cells, activation of OR2H2 by aldehyde 13-13 restored proliferation, and reduced the expression of senescence markers, P16 and P19. Additionally, aldehyde 13-13 induced apoptosis of H2O2-induced senescent cells, compared with non-senescent normal cells. In vivo, aldehyde 13-13 increased the lifespan of Caenorhabditis elegans and budding yeast. These findings demonstrate that OR2H2 is a functional receptor in VK2/E6E7 cells, and that activation of OR2H2 activates the AMPK-autophagy axis, and suppresses cellular aging and senescence, which may increase cellular health.

Hybridization of short-range and long-range charge transfer excited states in multiple resonance emitter.

Multiple resonance (MR) thermally activated delayed fluorescence emitters have been actively studied as pure blue dopants for organic light-emitting diodes (OLEDs) because of excellent color purity and high efficiency. However, the reported MR emitter, 2,5,13,16-tetra-tert-butylindolo[3,2,1-jk]indolo[1',2',3':1,7]indolo[2,3-b]carbazole (tDIDCz) based on bis-fused indolocarbazole framework could not demonstrate efficient triplet-to-singlet spin crossover. In this work, we report two isomeric MR emitters designed to promote triplet exciton harvesting by reconstructing the electronic structure of tDIDCz. To manage excited states, strong electron donors were introduced at the 2,5-/1,6-position of tDIDCz. As a result, 2,5-positions managed tDIDCz shows long-range charge transfer characteristics while preserving the MR nature. Quantum chemical calculation demonstrates direct spin-orbit coupling by long-range charge transfer and spin-vibronic coupling assisted reverse intersystem crossing by short-range charge transfer simultaneously contribute to triplet-to-singlet spin crossover. Consequently, high performance blue OLED recorded a high external quantum efficiency of 30.8% at a color coordinate of (0.13, 0.13).

Color Stable Deep Blue Multi-Resonance Organic Emitters with Narrow Emission and High Efficiency.

The development of highly efficient and deep blue emitters satisfying the color specification of the commercial products has been a challenging hurdle in the organic light-emitting diodes (OLEDs). Here, deep blue OLEDs with a narrow emission spectrum with good color stability and spin-vibronic coupling assisted thermally activated delayed fluorescence are reported using a novel multi-resonance (MR) emitter built on a pure organic-based molecular platform of fused indolo[3,2,1-jk]carbazole structure. Two emitters derived from 2,5,11,14-tetrakis(1,1-dimethylethyl)indolo[3,2,1-jk]indolo[1',2',3':1,7]indolo[3,2-b]carbazole (tBisICz) core are synthesized as the MR type thermally activated delayed fluorescence emitters realizing a very narrow emission spectrum with a full-width-at-half-maximum (FWHM) of 16 nm with suppressed broadening at high doping concentration. The tBisICz core is substituted with a diphenylamine or 9-phenylcarbazole blocking group to manage the intermolecular interaction for high efficiency and narrow emission. The deep blue OLEDs achieve high external quantum efficiency (EQE) of 24.9%, small FWHM of 19 nm, and deep blue color coordinate of (0.16, 0.04) with good color stability with increase in doping concentration. To the authors' knowledge, the EQE in this work is one of the highest values reported for the deep blue OLEDs that achieve the BT.2020 standard.

Effects of tomato ketchup and tomato paste extract on hepatic lipid accumulation and adipogenesis.

Tomatoes include high levels of lycopene, which is a potent antioxidative, hypolipidemic, and antidiabetic phytochemical. The intake of lycopene is associated with a reduced risk of insulin resistance and metabolic syndrome. The aim of this study was to investigate whether tomato ketchup and tomato paste, major dietary sources for tomato and lycopene, could regulate hepatic lipid metabolism and adipogenesis. To investigate the regulatory effects of tomato ketchup and tomato paste, we prepared a tomato ketchup extract (TKE) and a tomato paste extract (TPE) in 80% (v/v) ethyl acetate for the experiment. TKE and TPE reduced lipid accumulation and key markers for gluconeogenesis and induced a higher rate of fatty acid oxidation in HepG2 hepatocytes. In 3T3-L1 adipocytes, TKE and TPE increased adipogenesis and intracellular triglyceride accumulation, and stimulated glucose uptake. Peroxisome proliferator-activated receptor alpha and gamma expression levels were increased by TKE and TPE treatment. A single oral dose of tomato ketchup and tomato paste (9.28 g/kg) significantly improved glucose and insulin tolerance in mice. These findings suggest that lycopene-containing tomato ketchup and tomato paste may have beneficial regulatory effects in terms of energy metabolism in hepatocytes and adipocytes, and thus may improve blood glucose metabolism.

Asymmetric Decoration of a meta-Linked Bitriazine-Based Host for Highly Efficient and Stable Blue Phosphorescent Organic Light-Emitting Diodes.

High triplet energy hosts for blue phosphorescent organic light-emitting diodes were developed by decorating a meta-linked bitriazine core with carbazole and tetraphenylsilyl functional groups. A symmetric host with two carbazole units as the two triazine units of the core and an asymmetric host with one carbazole unit and one tetraphenylsilyl unit as the two triazine units were prepared. The triplet energy of these two hosts was 2.97 eV, suitable for triplet exciton harvesting of blue phosphors. Comparing the two host designs, the asymmetric decoration of the two triazine units with carbazole and tetraphenylsilyl units was superior to the symmetric decoration of the two triazine units with two carbazoles in terms of high external quantum efficiency (EQE) and long-term device stability. A high EQE of 19.7% and a long device lifetime of 2093.6 h at 100 cd m-2 were achieved using the asymmetrical host.

Sensory test A-Not A rating signal detection: Panel's sensory learning and stability of decision criteria.

Signal detection theory (SDT) sensory discrimination analysis using A-Not A with a two-step rating is an efficient approach to in-house sensory quality management in the food industry. For such sensory analysis using an internal panel, the panels' ability to use stable decision criteria and provide a consistent response distribution responding to "A" vs "Not A" is critical for guaranteeing the data quality. This study examined the effects of the familiarization procedure (FP) and reference presentation probability (RPP) in the SDT A-Not A rating protocol on the panels' sensory learning of samples and stability of decision criteria using SDT parameters, recognition d' (d'Rec),criteria location (c), and discrimination d' indices. Three different protocols were compared using ice-tea samples with small differences: Control, 0.25 RPP with repeated reference tasting (FPR); Modified-1, 0.25 RPP with reference categorization (FPC); Modified-2, 0.5 RPP with reference categorization (FPC). An independent sample design with three groups having equal sensitivity was used to identify the differences among the protocols. For each protocol, two sub-groups with similar decision criteria (response bias) were formed according to the results obtained from the pre-test and used for the main-test analysis. SDT analysis results indicated that the Modified-2 protocol with a higher RPP (0.5) induced the most efficient sensory learning of the reference. The protocol improved the subjects' recognition of the reference and test samples, better differentiating from the reference and stabilizing the decision criterion, resulting in higher discrimination performance (larger d'). The results showed that d'Rec analysis, together with d' analysis using a sensory panel, is a useful tool for monitoring the panel performance and checking for the sensory data quality of the sensory difference tests. In the present paper, a detailed illustration of the A-Not A sensory test procedure and examples of how to apply the SDT indices for different business decision-making is also introduced using the design and results of the present experiment.

OR2AT4, an Ectopic Olfactory Receptor, Suppresses Oxidative Stress-Induced Senescence in Human Keratinocytes.

Olfactory receptors (ORs) are the largest protein superfamily in mammals. Certain ORs are ectopically expressed in extranasal tissues and regulate cell type-specific signal transduction pathways. OR2AT4 is ectopically expressed in skin cells and promotes wound healing and hair growth. As the capacities of wound healing and hair growth decline with aging, we investigated the role of OR2AT4 in the aging and senescence of human keratinocytes. OR2AT4 was functionally expressed in human keratinocytes (HaCaT) and exhibited co-expression with G-protein-coupled receptor signaling components, Golfα and adenylate cyclase 3. The OR2AT4 ligand sandalore modulates the intracellular calcium, inositol phosphate, and cyclic adenosine monophosphate (cAMP) levels. The increased calcium level induced by sandalore was attenuated in cells with OR2AT4 knockdown. OR2AT4 activation by sandalore inhibited the senescent cell phenotypes and restored cell proliferation and Ki-67 expression. Sandalore also inhibited the expression of senescence-associated ß-galactosidase and increased p21 expression in senescent HaCaT cells in response to hydrogen peroxide. Additionally, sandalore activated the CaMKKß/AMPK/mTORC1/autophagy signaling axis and promoted autophagy. OR2AT4 knockdown attenuated the increased in the intracellular calcium level, cell proliferation, and AMPK phosphorylation induced by sandalore. These findings demonstrate that the effects of sandalore are mediated by OR2AT4 activation. Our findings suggest that OR2AT4 may be a novel therapeutic target for anti-aging and anti-senescence in human keratinocytes.

Multiple-Resonance Extension and Spin-Vibronic-Coupling-Based Narrowband Blue Organic Fluorescence Emitters with Over 30% Quantum Efficiency.

Achieving narrow-bandwidth emission and high external quantum efficiency (EQE) simultaneously is a challenge for next-generation blue-emitting organic light-emitting diodes (OLEDs). In this study, novel multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitters are developed by fusing an indolocarbazole unit with two carbazole skeletons using para-oriented nitrogen atoms. The resulting rigid and planar π-system without electron-accepting atoms exhibits pure blue photoluminescence at 470 nm, reaching a 100% quantum yield with a full-width-at-half-maximum (FWHM) of 25 nm. Higher-level quantum chemistry calculations confirm an MR effect within the extended π-conjugation and an enhanced triplet-to-singlet crossover (104 s-1 ) through a reduced energy gap (ΔEST ) coupled with large spin-vibronic coupling mediated by low-lying triplet excited states. An OLED fabricated using the MR-TADF emitter with CIE color coordinates of (0.12, 0.16) exhibits a record high EQE of 30.9% and a small FWHM of 23 nm. With further optimization of the device structure, a high EQE of 33.8% is achieved without additional outcoupling enhancements owing to the near-perfect horizontal alignment of the emitting dipoles.

Purely Spin-Vibronic Coupling Assisted Triplet to Singlet Up-Conversion for Real Deep Blue Organic Light-Emitting Diodes with Over 20% Efficiency and y Color Coordinate of 0.05.

Finding narrow-band, ultrapure blue thermally activated delayed fluorescence (TADF) materials is extremely important for developing highly efficient organic light-emitting diodes (OLEDs). Here, spin-vibronic coupling (SVC)-assisted ultrapure blue emitters obtained by joining two carbazole-derived moieties at a para position of a phenyl unit and performing substitutions using several blocking groups are presented. Despite a relatively large singlet-triplet gap (∆EST ) of >0.2 eV, efficient triplet-to-singlet crossover can be realized, with assistance from resonant SVC. To enhance the spin crossover, electronic energy levels are fine-tuned, thereby causing ∆EST to be in resonance with a triplet-triplet gap (∆ETT ). A sizable population transfer between spin multiplicities (>103 s-1 ) is achieved, and this result agrees well with theoretical predictions. An OLED fabricated using a multiple-resonance-type SVC-TADF emitter with CIE color coordinates of (0.15, 0.05) exhibits ultrapure blue emissions, with a narrow full-width-at-half-maximum of 21 nm and a high external quantum efficiency of 23.1%.

Lifetime-Extending 3-(4-Phenylbenzo[4,5]thieno[3,2-d]pyrimidin-2-yl)benzonitrile Acceptor for Thermally Activated Delayed Fluorescence Emitters.

Highly efficient and long-living green thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs) were developed using benzothienopyrimidine-4-benzonitrile acceptor-derived compounds as the TADF emitters. A molecular design merging the benzothienopyrimidine-4-benzonitrile acceptor with either indolocarbazole or diindolocarbazole was employed to prepare two TADF emitters, 5-(2-phenylbenzo[4,5]thieno[3,2-d]pyrimidin-4-yl)-2-(5-phenylindolo[3,2-a]carbazol-12(5H)-yl)benzonitrile and 2-(10,15-diphenyl-10,15-dihydro-5H-diindolo[3,2-a:3',2'-c]carbazol-5-yl)-5-(2-phenylbenzo[4,5]thieno[3,2-d]pyrimidin-4-yl)benzonitrile (BTPDIDCz), as the green and greenish-yellow emitters. Among the two emitters, BTPDIDCz with the diindolocarbazole donor combined with the benzothienopyrimidine-4-benzonitrile acceptor demonstrated a high external quantum efficiency of 24.5% and 3 times longer device lifetime than the state-of-the-art green emitter. This work proposed the potential of benzothienopyrimidine-4-benzonitrile as the acceptor for long lifetime in TADF emitters.

Narrowband and Pure Violet Organic Emitter with a Full Width at Half Maximum of 14 nm and y Color Coordinate of Below 0.02.

Violet organic light-emitting diodes (OLEDs) with a very narrow emission spectrum with a full width at half maximum of 14 nm and y color coordinate of 0.02 are developed using a indolo[3,2,1-jk]carbazole-derived pure violet emitter. The violet emitter, 2,5,13,16-tetra-tert-butylindolo[3,2,1-jk]-indolo[1',2',3':1,7]indolo[2,3-b]carbazole (tDIDCz), is designed to have a very rigid molecular structure driven by the multiresonance-type core structure through the alternating carbon and nitrogen atoms. The violet emitter is decorated with t-butyl groups to prevent intermolecular aggregation and packing, which allow pure violet emission without excimer emission. The violet OLEDs derived from the tDIDCz emitter show a violet color coordinate of (0.164, 0.018) with a narrow emission spectrum and a full width at half maximum of 14 nm (105 meV). The external quantum efficiency of the pure violet OLEDs is 3.3%. This is the first work reporting pure violet emission without any ultraviolet emission below 380 nm and blue emission above 450 nm by showing a very narrow emission spectrum.

Recent Progress of the Lifetime of Organic Light-Emitting Diodes Based on Thermally Activated Delayed Fluorescent Material.

Recently, the external quantum efficiency and lifetime of organic light-emitting diodes (OLEDs) have been dramatically upgraded due to development of organic materials and device structure. In particular, an intramolecular or intermolecular complex based on thermally activated delayed fluorescent (TADF) materials has greatly contributed to improving OLED device performance. Although high external quantum efficiency has been the main objective of the development of TADF materials as hosts and emitters, recent interest has been directed towards the lifetime of TADF-material-based OLEDs. For the past several years, remarkable advances in the lifetime of phosphorescent and TADF OLEDs have been made using TADF materials as hosts or emitters in the emitting layer. Therefore, since TADF materials are useful as both hosts and emitters for a long lifetime, this work discusses the recent progress made in developing TADF materials for long-lifetime OLEDs.

Rational Molecular Design Overcoming the Long Delayed Fluorescence Lifetime and Serious Efficiency Roll-Off in Blue Thermally Activated Delayed Fluorescent Devices.

Blue thermally activated delayed fluorescent (TADF) devices with short excited-state lifetime, high reverse intersystem crossing rate, and low-efficiency roll-off were developed by managing the molecular structure of donor-acceptor-type blue emitters. Three isomers of blue TADF emitters with a diphenyltriazine acceptor and three carbazole donors were synthesized. The position of the donor moieties in the phenyl linker connecting the donor and acceptor moieties was controlled to devise compounds with a short delayed fluorescence lifetime. A blue TADF emitter with three carbazole donors at 2-, 3-, and 4- positions of a phenyl linker shortened the excited state lifetime to 4.1 µs, showed a high external quantum efficiency of 20.4 %, and low efficiency roll-off of less than 10 % at 1000 cd m-2 . Therefore, a molecular design distorting the donors by aligning them in a consecutive way is useful to resolve the issues of long delayed fluorescence lifetime and efficiency roll-off of blue TADF devices.

Improved protocols for histamine sensitization testing of acellular pertussis vaccines.

The histamine sensitization test is a widely used method for measuring the residual toxicity of pertussis toxin in acellular pertussis vaccines. Although it has been used as a routine assay for decades, the current protocols are difficult to standardize because the test results vary considerably and are based on several factors, including mouse strain, age and sex. In this study, we observed that mice of strains CD1, ddY and C57/BL6 were sufficiently sensitive to pertussis toxin among six mice strains tested and that aged male mice were more sensitive to pertussis toxin than younger or female mice. Using this animal model, we showed pertussis toxin dose-dependent responses in the two histamine sensitization test protocols based on either lethal end-point determination or mouse rectal temperature measurement. Sensitivity to pertussis toxin was further enhanced by the addition of lipopolysaccharide in both methods. With these improvements, pertussis toxin activity can be estimated more accurately and reproducibly using a reduced number of animals.

Amyotrophic lateral sclerosis with an acute hypertensive crises.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving the systemic motor neurons, but autonomic nervous function is relatively well preserved. A few studies related to autonomic dysfunction have been reported, but autonomic dysfunction is rare in ALS. Moreover, dysautonomia symptoms are not prominent in patients with ALS. We present a 55-year-old male patient with ALS, who had acute severe hypertension and tachycardia crises, as well as sudden falls in his blood pressure. After he was diagnosed with ALS, he suddenly collapsed and was placed under mechanical ventilation. Several hypertensive attacks and dysautonomic signs then occurred. We successfully controlled the dysautonomia using diazepam and doxazocin mesylate, an alpha receptor antagonist.

Lance-adams syndrome.

Lance-Adams syndrome (LAS) is a rare complication of successful cardiopulmonary resuscitation and is often accompanied by action myoclonus. LAS is seen in patients who have undergone a cardiorespiratory arrest, later regained consciousness, and then developed myoclonus days or weeks after the event. Less than 150 cases of LAS have been reported in the worldwide medical literature. Here, we present a 32-year-old man who suffered from myoclonus after hypoxic brain damage due to hanging himself. This case was diagnosed as Lance-Adams syndrome according to a history of hypoxic brain damage, the clinical features, and the neuroimages such as brain SPECT. Making an early diagnosis and properly managing LAS is positively related to improving the patient's functional outcome. If patients have posthypoxic myoclonus after successful cardiopulmonary resuscitation, we should consider the diagnosis of LAS and initiate a proper rehabilitation program.