BN-embedded nonacene, tridecacene, and heptadecacene frameworks were constructed using one-shot quadruple, sextuple, and octuple borylation reactions, respectively. The key to success is the ...judicious choice of borylating reagents and long-chain alkyl-substituted carbazolyl groups as boron-trapping groups, which suppressed the decrease in HOMO energy and insolubilization associated with borylation. Based on the product yields, each electrophilic C–H borylation proceeded in >99% yield, which is the best efficiency reported so far for C–H borylation reactions. Owing to the multiple resonance effects of boron and nitrogen, the prepared acenes exhibited ultra-narrowband green thermally activated delayed fluorescence with full-width at half-maximum of 12–16 nm; moreover, their k RISC values were in the order of 105 s–1. We fabricated an organic light-emitting diode by employing the nonacene as an emitter, which exhibited high external quantum efficiency (EQE) of 28.7%. The device also showed a minimum efficiency roll-off with an EQE of 25.8% at 1000 cd m–2.
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IJS, KILJ, NUK, PNG, UL, UM
Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (1) and erythro-2-amino-1,2-diphenylethanol (2) has been demonstrated. The stereochemistry of the deposited ...salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from 1H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic 2, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of 1 and 2.
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IJS, KILJ, NUK, PNG, UL, UM
Hypophosphatasia (HPP) is a systemic skeletal disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). We recently reported that survival of HPP model mice ...can be prolonged using an adeno-associated virus (AAV) vector expressing bone-targeted TNALP with deca-aspartate at the C terminus (TNALP-D
10
); however, abnormal bone structure and hypomineralization remained in the treated mice. Here, to develop a more effective and clinically applicable approach, we assessed whether transfection with TNALP-D
10
expressing virus vector at a higher dose than previously used would ameliorate bone structure defects. We constructed a self-complementary AAV8 vector expressing TNALP driven by the chicken beta-actin (CBA) promoter (scAAV8-CB-TNALP-D
10
). The vector was injected into both quadriceps femoris muscles of newborn HPP mice at a dose of 4.5 × 10
12
vector genome (v.g.)/body, resulting in 20 U/mL of serum ALP activity. The 4.5 × 10
12
v.g./body-treated HPP mice grew normally and displayed improved bone structure at the knee joints in X-ray images. Micro-CT analysis showed normal trabecular bone structure and mineralization. The mechanical properties of the femur were also recovered. Histological analysis of the femurs demonstrated that ALP replacement levels were sufficient to promote normal, growth plate cartilage arrangement. These results suggest that AAV vector-mediated high-dose TNALP-D
10
therapy is a promising option for improving the quality of life (QOL) of patients with the infantile form of HPP.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The mechanical durability of our hydrocarbon polymer electrolyte membrane, poly(sulfophenylene quinquephenylene) (SPP-QP) or polyphenylene ionomer, was evaluated in wet/dry cycle tests in fuel cells ...according to the US-DOE protocol, where the effect of gas diffusion layers (hard or soft GDL) was investigated. The membrane exhibited mechanical failure with the hard GDL and H2 crossover (permeation through the membrane) jumping from 0.01% to ca. 2% after 4,000 cycles. Post-test analyses indicated that the edge of the membrane under the gasket was the most damaged, where the dimensional change upon humidification/dehumidification was restricted. Use of the soft GDL significantly improved the wet/dry cycle durability of the membrane with no practical changes in the H2 crossover, even after 30,000 cycles, due to the strong adhesion of the GDL to the catalyst layers. The mechanical durability of the SPP-QP membrane was better than that of our previous aromatic-based ionomer membrane containing ether and ketone groups in the main chain. The loss of molecular weight and the sulfonic acid groups was rather minor for the SPP-QP membrane, indicating chemical robustness of the membrane under the severe wet/dry cycle conditions.
•Sulfonated polyphenylene ionomer membranes are durable in wet/dry cycling in fuel cells.•Soft gas diffusion layer improves significantly mechanical durability of the ionomer membranes.•Strong adhesion of the gas diffusion layer to the catalyst layer prevents mechanical failure of the membrane.•Structural changes (loss of molecular weight and sulfonic acid groups) of the membrane are minor after 30,000 wet/dry cycles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Background and Objective
The relative effectiveness of initial non‐invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high‐flow nasal ...cannula (HFNC) is unclear.
Methods
We conducted a multicenter, open‐label, parallel‐group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days.
Results
Eighty‐five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio HR, 0.327; 95% CI, 0.148–0.724; p = 0.006). There were no significant between‐group differences in the intubation rates, in‐hospital and 28‐day mortality rates, ventilator‐free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events.
Conclusion
CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.
In patients with acute hypoxemic respiratory failure, compared with high‐flow nasal cannula oxygen therapy, continuous positive airway pressure reduced the risk of meeting the criteria for intubation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We examined whether inferior thyroid artery peak systolic velocity (ITA-PSV) predicts an increase in levothyroxine (LT4) dosage in pregnant women with Hashimoto's thyroiditis.
Twenty-two women with ...Hashimoto's thyroiditis who were planning and later achieved pregnancy or confirmed as pregnant were enrolled in this retrospective longitudinal observational study. ITA-PSV and thyroid volume were measured using ultrasonography. Serum concentrations of free thyroxine (F-T4), free triiodothyronine (F-T3), and thyroid stimulating hormone (TSH) were simultaneously determined. We adjusted LT4 dosage to maintain serum TSH at < 2.5 μIU/mL (1st trimester) and later at < 3 μIU/mL (2nd, 3rd trimester).
Eighteen patients (81.8%) required an increase in LT4 dosage during pregnancy, of whom 7 (31.8%) required an increase ≥50 μg. Multivariable regression analysis showed that TSH (β = 0.507, p = 0.008) and ITA-PSV (β = - 0.362, p = 0.047), but not thyroid volume, F-T4, or F-T3, were independently associated with increased LT4 dosage. Receiver-operating characteristic analysis for predicting an increase in LT4 ≥ 50 μg/day showed that the area under the curve (0.905) for ITA-PSV with TSH was not significantly increased (p = 0.123) as compared to that (0.743) for TSH alone, whereas integrated discrimination improvement was significantly increased (27.9%, p = 0.009).
In pregnant patients with Hashimoto's thyroiditis, ITA-PSV was a significant predictor of increase in LT4 dosage independent of TSH level, while ITA-PSV plus TSH showed significantly improved predictability as compared to TSH alone. These results suggest that ITA-PSV reflects residual thyroid function and is useful for evaluating the need for increased thyroid hormone production in pregnant patients with Hashimoto's thyroiditis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Recently, the daily environment for children in Japan has been changing because of the significantly declining birthrate. The purpose of this study was to investigate the actual conditions of new ...child patients visiting the pediatric dentistry department of two different college hospitals as well as regional differences. The subjects were children under 16 years old who visited the Pediatric Dentistry Department of Tokyo Dental College Suidobashi Hospital (hereafter "Suidobashi") or the Chiba Dental Center (hereafter "Chiba") from 2016 to 2018. The number of new patients, age at first consultation, chief complaint and status of dental caries were determined, with the following results.1.The number of new patients under 16 years old was 2,538 at Suidobashi, and 2,850 at Chiba. The number has been increasing annually at Suidobashi, while it has been decreasing at Chiba.2.At both hospitals, dental caries was the most common chief complaint of new patients (Suidobashi: 40.0%, Chiba: 39.6%), followed by malocclusion (Suidobashi: 19.3%, Chiba: 18.3%). When divided by age, the maximum number of patients primarily affected by dental caries was found in the 2-year-old group at Suidobashi and in the 4-year-old group at Chiba.3.The highest caries prevalence rate in deciduous dentition was shown in 4-year-old patients (70.2%) at Suidobashi, and 3-year-old patients (56.6%) at Chiba.4.As for df index, the highest values at both hospitals were seen in patients aged 4 years (Suidobashi: 40.7%, Chiba: 43.5%).5.Among younger children, there were more patients with severe dental caries at Suidobashi than at Chiba.
sp. P1 shows an acidophilic phenotype which could allow mass-scale monoculture of this green microalga without severe contamination by environmental microorganisms. In this study, we report a ...chromosome-scale genome assembly for
sp. P1.
IκB kinase β (IKK-β) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-κB) in response to various inflammatory stimuli. ...We have identified a small molecule inhibitor of IKK-β. Optimization of the lead compound resulted in improvements in both in vitro and in vivo potency, and provided IKK-β inhibitors exhibiting potent activity in an acute cytokine release model (LPS-induced TNFα).
Graphic
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
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A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as I
κB kinase β (IKK-β) inhibitors. Modification of a novel IKK-β inhibitor
1 (IKK-β ...IC
50
=
1500
nM, Cell IC
50
=
8000
nM) at the 4-phenyl ring and 6-phenol group on the pyridine core ring resulted in a marked increased in biological activities. An optimized compound, 2-amino-6-2-(cyclopropylmethoxy)-6-hydroxyphenyl-4-piperidin-4-yl nicotinonitrile, exhibited excellent in vitro profiles (IKK-β IC
50
=
8.5
nM, Cell IC
50
=
60
nM) and a strong oral efficacy in in vivo anti-inflammatory assays (significant effects at 1
mg/kg, po in arachidonic acid-induced ear edema model in mice).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
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