Protective effects of imeglimin on the development of atherosclerosis in ApoE KO mice treated with STZ.

BACKGROUND: Imeglimin is a new anti-diabetic drug which promotes insulin secretion from pancreatic ß-cells and reduces insulin resistance in insulin target tissues. However, there have been no reports examining the possible anti-atherosclerotic effects of imeglimin. In this study, we investigated the possible anti-atherosclerotic effects of imeglimin using atherosclerosis model ApoE KO mice treated with streptozotocin (STZ). METHODS: ApoE KO mice were divided into three groups: the first group was a normoglycemic group without injecting STZ (non-DM group, n = 10). In the second group, mice were injected with STZ and treated with 0.5% carboxymethyl cellulose (CMC) (control group, n = 12). In the third group, mice were injected with STZ and treated with imeglimin (200 mg/kg, twice daily oral gavage, n = 12). We observed the mice in the three groups from 10 to 18 weeks of age. Plaque formation in aortic arch and expression levels of various vascular factors in abdominal aorta were evaluated for each group. RESULTS: Imeglimin showed favorable effects on the development of plaque formation in the aortic arch in STZ-induced hyperglycemic ApoE KO mice which was independent of glycemic and lipid control. Migration and proliferation of vascular smooth muscle cells and infiltration of macrophage were observed in atherosclerotic lesions in STZ-induced hyperglycemic ApoE KO mice, however, which were markedly reduced by imeglimin treatment. In addition, imeglimin reduced oxidative stress, inflammation and inflammasome in hyperglycemic ApoE KO mice. Expression levels of macrophage makers were also significantly reduced by imeglimin treatment. CONCLUSIONS: Imeglimin exerts favorable effects on the development of plaque formation and progression of atherosclerosis.

[A Case of Recurrent Gastric GIST with Long-Term Survival after Multidisciplinary Treatment].

An 80-year-old male patient presented with a 2.5 cm-sized submucosal tumor on the greater curvature side of the upper gastric body during an endoscopic examination in 200X. We diagnosed gastric GIST by biopsy and performed laparoscopic- assisted partial gastrectomy. Imatinib was started as postoperative adjuvant therapy, but was discontinued after 1 month due to eyelid edema. The patient was followed up with a contrast-enhanced CT scan and a PET-CT scan. A 7 cm-sized mass in the gastrosplenic region was discovered on a 200X+7 years CT scan; this mass was thought to be possible recurrence of peritoneal dissemination. The patient did not want to undergo surgery or drug treatment, and was followed up. Five months later he complained of abdominal pain. The CT scan showed that the mass had shrunk slightly, but a small amount of ascites was observed, and tumor rupture was suspected. Therefore, we performed resection of the tumor in the office. Numerous disseminated nodules were found in the intra-abdominal cavity. Pathological examination revealed recurrence of GIST, and the patient was started on imatinib 200 mg/day. The dose was temporarily increased to 300 mg/day, but was reduced again to 200 mg/day 1 month later due to eyelid edema. Thereafter, the dose was temporarily discontinued due to stomatitis, and from 200X+8 years, 200 mg/day was administered for 2 weeks and then discontinued for 2 weeks. At present, 14 years after the first surgery and 6 years after recurrence, he remains alive thanks to imatinib continuation.

[Development of Analytical Method and Surveillance ofGibberellic Acid in Banana, Cherry, and Kiwi Fruit].

Gibberellic acid (GA3) is commonly used as a plant growth regulator in many food crops owing to its essential signaling functions during plant growth and development. In Japan, a threshold for administrative action for GA3 content of 0.3 mg/kg applies in produce in which maximum residue limits have not been established. Although the threshold is based on previous studies, the GA3 concentrations in individual foods are still unknown. Thus, we surveyed the concentrations of GA3 in banana, cherry, and kiwi fruit on the Japanese market. We developed and validated a method for the analysis of GA3 using solid-phase extraction and LC-MS/MS in accordance with accepted criteria of trueness, repeatability, and selectivity. The limits of detection and of quantification were determined as 0.005 and 0.05 mg/kg, respectively, in all fruits. Concentrations of GA3 did not exceed 0.3 mg/kg regardless of ripeness, suggesting the reasonability of the current regulation of GA3 in banana, cherry, and kiwi fruit. These findings can support prompt administrative action on these fruits, contributing to the regulation of GA3 in Japan.

One-Shot Synthesis of Expanded Heterohelicene Exhibiting Narrowband Thermally Activated Delayed Fluorescence.

An expanded heterohelicene consisting of three BN2-embedded [4]helicene subunits (V-DABNA-Mes) has been synthesized by one-shot triple borylation. The key to success is the excessive use of boron tribromide in an autoclave. Based on the multiple resonance effect of three boron and six nitrogen atoms, V-DABNA-Mes exhibited a narrowband sky-blue thermally activated delayed fluorescence with a full width at half-maximum of 16 nm. The resonating π-extension minimized the singlet-triplet energy gap and enabled rapid reverse intersystem crossing with a rate constant of 4.4 × 105 s-1. The solution-processed organic light-emitting diode device, employed as an emitter, exhibited a narrowband emission at 480 nm with a high external quantum efficiency of 22.9%.

Influence of MDR1 gene polymorphism (2677G>T) on expression and function of P-glycoprotein at the blood-brain barrier: utilizing novel P-glycoprotein humanized mice with mutation.

P-glycoprotein, the encoded product of the MDR1 / ABCB1 gene in humans, is expressed in numerous tissues including brain capillary endothelial cells and restricts the distribution of xenobiotics into the brain as an efflux pump. Although a large number of single nucleotide polymorphisms in the MDR1 gene have been identified, the influence of the nonsynonymous 2677G>T/A single nucleotide polymorphism on P-glycoprotein at the blood-brain barrier has remained unclear. In the present study, we developed a novel P-glycoprotein humanized mouse line carrying the 2677G>T mutation by utilizing a mouse artificial chromosome vector constructed by genetic engineering technology and we evaluated the influence of 2677G>T on the expression and function of P-glycoprotein at the blood-brain barrier in vivo . The results of this study showed that the introduction of the 2677G>T mutation does not alter the expression levels of P-glycoprotein protein in the brain capillary fraction. On the other hand, the brain penetration of verapamil, a representative substrate of P-glycoprotein, was increased by the introduction of the 2677G>T mutation. These results suggested that the 2677G>T single nucleotide polymorphism may attenuate the function of P-glycoprotein, resulting in increased brain penetration of P-glycoprotein substrates, without altering the expression levels of P-glycoprotein protein in the blood-brain barrier. This mutant mouse line is a useful model for elucidating the influence of an MDR1 gene single nucleotide polymorphism on the expression and function of P-glycoprotein at the blood-brain barrier.

A cross-sectional study on metabolic similarities and differences between inpatients with schizophrenia and those with mood disorders.

BACKGROUND: One of the main causes of death in psychiatric patients is cardiovascular diseases which are closely related with lifestyle-related diseases. Psychiatric disorders include schizophrenia and mood disorders, whose symptoms and treatment medicines are different, suggesting that they might have different metabolic disorders. Thus, we studied the differences of lifestyle-related diseases between schizophrenia and mood disorders in Japan. METHODS: This cross-sectional study was performed from 2015 to 2017. Study participants were 189 Japanese hospitalized patients (144 schizophrenia group, 45 mood disorders group) in the department of psychiatry at Kohnodai hospital. We examined physical disorders, metabolic status of glucose and lipid, estimated glomerular filtration rate (eGFR) and brain magnetic resonance imaging. We compared these data between schizophrenia and mood disorders groups using analysis of covariance or logistic regression analysis. In comparisons between inpatients with schizophrenia or mood disorders group and the standard, we quoted 'The National Health and Nutrition Survey in Japan 2015' by Ministry of Health, Labor and Welfare as the standard. RESULTS: eGFR and prevalence of smoking were significantly lower in patients with mood disorder group than those with schizophrenia group by adjustment for age. In comparisons between patients with schizophrenia group or mood disorders group and each standard, the ratio of silent brain infarction (SBI) and cerebral infarction were significantly high in both groups. Schizophrenia group showed significantly higher prevalence of diabetes, low high-density lipoprotein (HDL) cholesterolemia, metabolic syndrome and smoking than the standard. Mood disorders group had significantly high prevalence of low HDL-cholesterolemia compared with the standard. Fasting blood glucose and HbA1c were significantly higher in schizophrenia group and female mood disorders group than the standard. Female mood disorders group had significantly decreased eGFR with increased ratio of eGFR < 60 ml/min than the standard. CONCLUSIONS: Participants of both groups had increased ratio of SBI and cerebral infarction, accompanied with glucose and lipid disorders. Compared with schizophrenia group, mood disorders group showed significantly low eGFR and prevalence of smoking.

Comparison of the hepatic metabolism of triazolam in wild-type andCyp3a-knockout mice for understanding CYP3A-mediated metabolism inCYP3A-humanised mice in vivo.

1. To investigate cytochrome P450 3A (CYP3A)-mediated metabolism in vivo, plasma concentrations of triazolam (TRZ) are often monitored as a CYP3A marker in CYP3A-humanised mice. However, it has not been determined whether plasma concentrations of TRZ after intravenous administration can reflect hepatic CYP3A activity in CYP3A-humanised mice. 2. Firstly, we investigated the pharmacokinetics of TRZ in wild-type and Cyp3a-knockout (Cyp3a-KO) mice. Plasma concentration profiles of TRZ and α-hydroxy (OH) TRZ were very similar in wild-type and Cyp3a-KO mice. On the other hand, AUC of 4-OH TRZ in Cyp3a-KO mice was significantly lower than that in wild-type mice. Pregnenolone 16α-carbonitrile (PCN) decreased the areas under the plasma concentration-time curves (AUCs) of TRZ and α-OH TRZ in both groups. There was no significant effect of PCN on AUC of 4-OH TRZ in Cyp3a-KO mice. 3. Next, we verified that AUC of 4-OH TRZ in CYP3A-humanised mice was higher than that in Cyp3a-KO mice, although the difference was not significant. 4. In conclusion, plasma concentrations of 4-OH TRZ, but not those of TRZ and α-OH TRZ, might reflect hepatic CYP3A activity in mice in vivo. These results provide important insights for in vivo studies using a CYP3A-humanised model.

[A Case of Synchronous and Solitary Gallbladder Metastasis from Gastric Cancer].

A 60s woman was found to have wall thickening of the gastric body and gallbladder in the follow-up CT scan after surgery for cervical carcinoma. An endoscopic examination revealed a type 3 tumor, located in the lesser curvature of the middle stomach. Abdominal CT showed lymphadenopathy at the lesser curvature. An enhanced thickened wall was also noted in the fundus of the gallbladder. FDG-PET/CT showed negative uptake in the gallbladder lesion. Distal gastrectomy and cholecystectomy were performed under the preoperative diagnosis of gastric cancer and adenomyomatosis. Histopathologically, the gastric lesion was a poorly differentiated adenocarcinoma, SE, ly1c, v1b. Moreover, the gallbladder lesion was a poorly differentiated adenocarcinoma proliferating mainly in the muscularis propria and subserosa, which had similar histological features as those in the adenocarcinoma part of gastric cancer. From these findings, the patient was diagnosed with gallbladder metastasis from gastric cancer. Gastric cancer rarely metastasizes to the gallbladder, and only 16 cases have been reported in Japan. We present the clinicopathological features with a review of the literature.

Characterization of P-Glycoprotein Humanized Mice Generated by Chromosome Engineering Technology: Its Utility for Prediction of Drug Distribution to the Brain in Humans.

P-glycoprotein (P-gp), encoded by the MDR1 gene in humans and by the Mdr1a/1b genes in rodents, is expressed in numerous tissues and performs as an efflux pump to limit the distribution and absorption of many drugs. Owing to species differences of P-gp between humans and rodents, it is difficult to predict the impact of P-gp on pharmacokinetics and the tissue distribution of P-gp substrates in humans from the results of animal experiments. Therefore, we generated a novel P-gp humanized mouse model by using a mouse artificial chromosome (MAC) vector [designated human MDR1-MAC (hMDR1-MAC) mice]. The results showed that hMDR1 mRNA was expressed in various tissues of hMDR1-MAC mice. Furthermore, the expression of human P-gp was detected in the brain capillary fraction and plasma membrane fraction of intestinal epithelial cells isolated from hMDR1-MAC mice, although the expression levels of intestinal P-gp were extremely low. Thus, we evaluated the function of human P-gp at the blood-brain barrier of hMDR1-MAC mice. The brain-to-plasma ratios of P-gp substrates in hMDR1-MAC mice were much lower than those in Mdr1a/1b-knockout mice, and the brain-to-plasma ratio of paclitaxel was significantly increased by pretreatment with a P-gp inhibitor in hMDR1-MAC mice. These results indicated that the hMDR1-MAC mice are the first P-gp humanized mice expressing functional human P-gp at the blood-brain barrier. This mouse is a promising model with which to evaluate species differences of P-gp between humans and mice in vivo and to estimate the brain distribution of drugs in humans while taking into account species differences of P-gp.

Effect of Pregnenolone 16α-Carbonitrile on the Expression of P-Glycoprotein in the Intestine, Brain and Liver of Mice.

P-Glycoprotein (P-gp), encoded by the MDR1 (ABCB1) gene in humans and by Mdr1a and Mdr1b genes in rodents, is a member of the superfamily of ATP-binding cassette transporters. Since P-gp is constitutively expressed in numerous tissues and exhibits a broad specificity in substrate recognition, it can play a crucial role in limiting the absorption and distribution of xenobiotics by decreasing their intracellular accumulation. The expression of P-gp is regulated by various nuclear receptors such as pregnane X receptor (PXR). Although the characterization of P-gp induction by PXR ligands is a crucial goal for predicting pharmacokinetics of drugs, findings regarding the induction of P-gp by PXR ligands in vivo are still controversial. In this study, we examined the effect of pregnenolone 16α-carbonitrile (PCN), a murine PXR ligand, on the expression of Mdr1a/1b mRNA and P-gp protein in the intestine, brain and liver of mice. The results showed that PCN increased the expression of both Mdr1a/1b mRNA and P-gp protein in the intestine and the brain. The present study provided the first evidence that P-gp is inducible by PCN in the large intestine. The results also showed that P-gp protein was induced by PCN in the cortex but not in the whole brain. On the other hand, PCN increased the expression of Mdr1a/1b mRNA in the liver, although no increase was observed in the expression of P-gp protein. These results suggested different effect of PCN on the expression of P-gp protein in the intestine, brain and liver of mice.

Indirect activation of pregnane X receptor in the induction of hepatic CYP3A11 by high-dose rifampicin in mice.

Rifampicin (RIF), a typical ligand of human pregnane X receptor (PXR), powerfully induces the expression of cytochrome P450 3A4 (CYP3A4) in humans. Although it is thought that RIF is not a ligand of rodent PXR, treatment with high-dose RIF (e.g. more than 20 mg/kg) increases the expression of CYP3A in the mouse liver. In this study, we investigated whether the induction of CYP3A by high-dose RIF in the mouse liver is mediated via indirect activation of mouse PXR (mPXR). The results showed that high-dose RIF increased the expression of CYP3A11 and other PXR-target genes in the liver of wild-type mice but not PXR-knockout mice. However, the results of reporter gene and ligand-dependent assembly assays showed that RIF does not activate mPXR in a ligand-dependent manner. In addition, high-dose RIF stimulated nuclear accumulation of mPXR in the mouse liver, and geldanamycin and okadaic acid attenuated the induction of Cyp3a11 and other PXR-target genes in primary hepatocytes, suggesting that high-dose RIF triggers nuclear translocation of mPXR. In conclusion, the present study suggests that high-dose RIF stimulates nuclear translocation of mPXR in the liver of mice by indirect activation, resulting in the transactivation of Cyp3a11 and other PXR-target genes.

[Laparoscopic Surgery for an Intussusception Caused by Rectosigmoid Colon Cancer after Pre-Operative Reduction by Transanal Insertion of a Circular Sizer - A Case Report].

An octogenarian man complaining of bloody stool was referred to our hospital. A digital examination, abdominal enhanced CT and endoscopy led to a diagnosis of intussusception due to rectosigmoid colon cancer, but he was not suffering from bowel obstruction. An elective laparoscopic Hartmann's operation was performed after reduction by transanal insertion of a circular sizer. It may be difficult to reduce an intussusception induced by rectal cancer. We report this case with a review of the relevant literature.

MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment. In addition, we reasoned that the marijuana constituent cannabidiol (CBD) may provide benefit or could be proposed as an adjunct treatment in combination with antipsychotics. Hooded Lister rats were tested in the three-chamber version for social interaction, with an initial novelty phase, followed after 3 min by a short-term recognition memory phase. No drug treatment affected sociability. However, distinct effects on social recognition were revealed. MK-801 reduced social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1 mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced deficits. When CBD was combined with protective doses of aripiprazole (CBD-aripiprazole at 12 : or 5 : 2 mg/kg) the benefit of the antipsychotic was lost. At the same time, activity-related changes in behaviour were excluded as underlying reasons for these pharmacological effects. Collectively, the combined activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to provide a significant advantage over risperidone and olanzapine with respect to the rescue of cognitive deficits reminiscent of schizophrenia. The differential pharmacological properties of CBD, which are seemingly beneficial in human patients, did not back-translate and rescue the MK-801-induced social memory deficit.

Development of a processing factor prediction model for pesticides in processed tomato foods using elastic net regularization.

A novel regularized elastic net regression model was developed to predict processing factor (PF) for pesticide residues, which represents a change in the residue levels during food processing. The PF values for tomato juice, wet pomace and dry pomace in the evaluations and reports published by the Joint FAO/WHO Meeting on Pesticide Residues significantly correlated with the physicochemical properties of pesticides, and subsequently the correlation was observed in the present tomato processing study. The elastic net regression model predicted the PF values using the physicochemical properties as predictor variables for both training and test data within a 2-fold range for 80-100% of the pesticides tested in the tomato processing study while overcoming multicollinearity. These results suggest that the PF values are predictable at a certain degree of accuracy from the unique sets of physicochemical properties of pesticides using the developed model based on a processing study with representative pesticides.

Highly efficient multi-resonance thermally activated delayed fluorescence material toward a BT.2020 deep-blue emitter.

An ultrapure deep-blue multi-resonance-induced thermally activated delayed fluorescence material (DOB2-DABNA-A) is designed and synthesized. Benefiting from a fully resonating extended helical π-conjugated system, this compound has a small ΔEST value of 3.6 meV and sufficient spin-orbit coupling to exhibit a high-rate constant for reverse intersystem crossing (kRISC = 1.1 × 106 s-1). Furthermore, an organic light-emitting diode employing DOB2-DABNA-A as an emitter is fabricated; it exhibits ultrapure deep-blue emission at 452 nm with a small full width at half maximum of 24 nm, corresponding to Commission Internationale de l'Éclairage (CIE) coordinates of (0.145, 0.049). The high kRISC value reduces the efficiency roll-off, resulting in a high external quantum efficiency (EQE) of 21.6% at 1000 cd m-2.

An age-stratified cross-sectional study of antidiabetic and non-antidiabetic drugs prescribed to Japanese outpatients with diabetes.

Polypharmacy, common in patients with diabetes, may cause adverse drug reactions. The number of antidiabetic and non-antidiabetic drugs prescribed to patients in different age groups remains unclear. The aim of this study was to examine the number and class of antidiabetics and non-antidiabetics prescribed to Japanese patients with diabetes, stratified by age for reducing polypharmacy. This cross-sectional study examined all prescriptions of patients prescribed antidiabetics at 257 pharmacies of Matsumotokiyoshi Holdings in Japan from May 2018 to March 2019. Total prescription numbers including antidiabetic drugs were 263,915 in this study. Mean numbers of antidiabetic drugs per prescription were 1.71, 2.17, and 1.52 in the patient age groups of 10-19, 50-59, and 90-99 years, respectively. Count of antidiabetics was not related to age. However, the mean total number of drugs prescribed increased with age, which was 2.22 and 7.99 in the age groups of 10-19 and 90-99 years, respectively. The linear regression coefficient (b) according to age was 0.07 (p < 0.001) for 10-99 years. The mean non-antidiabetic number of agents prescribed increased with age among 10-99 years (b = 0.07, p < 0.001). Among outpatients treated for diabetes, dipeptidyl peptidase-4 inhibitors (29%) and antihypertensive, ß-blocking and renin-angiotensin system blocking drugs (32%) were the most prescribed antidiabetics and non-antidiabetics in all ages, respectively. The number of prescribed antidiabetic agents did not increase with age, whereas the total and non-antidiabetic numbers of medications prescribed increased linearly. For reduction of polypharmacy in older people with diabetes, we need to focus on non-antidiabetics.

The association between sarcopenia and functional outcomes in patients undergoing convalescent rehabilitation.

Sarcopenia is widely believed to be linked to poorer outcomes in inpatient rehabilitation. This study aimed to assess the impact of sarcopenia on functional outcomes and dietary intake during hospitalization in adults undergoing convalescent rehabilitation. We conducted a retrospective cohort analysis at a single rehabilitation institution. The Asian Working Group Consensus Criteria for Sarcopenia was used to diagnose. The Functional Independence Measure (FIM) score was used at hospital discharge to measure the primary functional outcome. Energy and protein intakes during hospitalization were calculated as part of the nutritional assessment. There were 126 patients in the research (median age, 73 yr;54% women). Stroke (n = 73;53.4% sarcopenia) and musculoskeletal disorders (n = 53;56.6% sarcopenia) were among the admission diagnoses. Multiple linear regression analysis revealed that the FIM total score at discharge was modestly associated with sarcopenia only in stroke patients (? = 0.1872, P = 0.09), as well as significantly and independently associated with protein intake during admission only in stroke patients (? = 0.3217, P < 0.05). In hospitalized stroke patients undergoing convalescent therapy, sarcopenia is related to lower functional results. Early identification of sarcopenia and treatment with rehabilitation nutrition should be implemented in this population. J. Med. Invest. 70 : 457-463, August, 2023.

Relationship between Phage Lytic Spectra and Sequence Types in Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolated in Japan.

The lytic spectrum of phages is usually limited to only a few strains of the same bacterial species that can lyse. In clinical molecular epidemiology, bacterial strains are commonly classified into sequence types (STs) using the multilocus sequence typing (MLST) approach. The aim of this study was to determine the association between the phage lytic spectrum and STs. MLST analysis of 11 extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli clinical isolates revealed that most belonged to ST73 or ST131, with four isolates each. Phages were isolated from sewage samples using various E. coli strains as hosts. The relationship between phage lytic spectra of ESBL-producing E. coli isolates ST73 and ST131 and STs was evaluated using Fisher's exact test. The lytic spectra of phages were significantly dependent on the ST classification of ST73 or ST131, suggesting that a phage lysing an isolate belonging to a particular ST could lyse other isolates of the same ST. We successfully isolated wide-host-range phages lysing all clinical isolates belonging to two clinically important ST types (ST73 and ST131).

Ultra-Narrowband Blue Multi-Resonance Thermally Activated Delayed Fluorescence Materials.

Ultra-narrowband blue multi-resonance-induced thermally activated delayed fluorescence (MR-TADF) materials (V-DABNA and V-DABNA-F), consisting of three DABNA subunits possessing phenyl or 2,6-difluorophenyl substituents on the peripheral nitrogen atoms are synthesized by one-shot triple borylation. Benefiting from the inductive effect of fluorine atoms, the emission maximum of V-DABNA-F (464 nm) is blueshifted from that of the parent V-DABNA (481 nm), while maintaining a small full width at half maximum (FWHM, 16 nm) and a high rate constant for reverse intersystem crossing (6.5 × 105 s-1 ). The organic light-emitting diodes (OLEDs) using V-DABNA and V-DABNA-F as emitters are fabricated by vapor deposition and exhibit blue emission at 483 and 468 nm with small FWHMs of 17 and 15 nm, corresponding to Commission Internationale d'Éclairage coordinates of (0.09, 0.27) and (0.12, 0.10), respectively. Both devices achieve high external quantum efficiencies of 26.2% and 26.6% at the maximum with minimum efficiency roll-offs of 0.9% and 3.2%, respectively, even at 1000 cd m-2 , which are record-setting values for blue MR-TADF OLEDs.