Selective encapsulation of carboxylic acid dimers within a size-regulable resorcinarene-based hemicarcerand.

A cavity within a resorcinarene-based hemicarcerand was contracted and expanded through conformational changes induced by the complexation and decomplexation, allowing self-sorting of homo- and heterodimeric carboxylic acid pairs.

Kinetic Resolution of Secondary Alcohols Catalyzed at the Exterior of Chiral Coordinated Capsules.

Confined spaces inside molecular hosts can function as reaction vessels. However, this concept significantly limits the scope of reactants. When the exterior of molecular hosts is used instead, we can ease the restriction because reactants are not necessary to be trapped inside molecular hosts, although studies along this line have not been reported. As a proof-of-concept of enantioselective reactions at the exterior of chiral molecular hosts, we utilized host-guest complexes of enantiomerically enriched Cu-coordinated capsules and guests possessing a catalytic center to realize the kinetic resolution of secondary alcohols. Under suitable reaction conditions, a selectivity factor of 2.6 was realized, demonstrating that the reactions occur at the exterior of the capsules. A series of experiments indicated that the substituents on the 2,2'-bipyridyl arms and the alkyl chains on the lower rim contributed to the enantioselectivity of the reactions.

Molecular Recognition Process in Resorcinarene-based Coordination Capsules.

Cu and Ag capsules can take up various organic molecules. Their molecular recognition possibly involves partial dissociation and slippage. We investigated molecular recognition processes in the Cu and Ag capsules by CD and 1 H NMR spectroscopy and employed 4,4'-diacetoxy biphenyl carrying two benzothiadiazole groups as a probe. CD and 1 H NMR measurements reveal that the host-guest complexation proceeds under second-order reactions and that these capsules undergo the partial dissociation to take up the probe in [D1 ]chloroform and [D8 ]THF. The slippage also contributes to host-guest complexation for a Cu capsule that carries p-methoxyphenyl groups on the 2,2'-bipyridiyl arms. DFT calculations suggest that π/π stacking interactions between the electron-rich p-methoxyphenyl group and the electron-poor 2,2'-bipyridyl arm elongate the capsule, allowing the guest to access the cavity without the partial dissociation.

RAD-Seq analysis of wild Japanese garlic (Allium macrostemon Bunge) growing in Japan revealed that this neglected crop was previously actively utilized.

Allium macrostemon Bunge, commonly referred to as "no-biru" in Japan, is a widespread wild onion species found across the country. Despite being deeply entwined in ancient Japanese culture, it remains an underutilized crop in Japan. Determining the origins of its domestic populations and understanding their genetic composition is crucial to highlighting the plant's historical significance in Japan. This study aims to bridge this knowledge gap by examining the genetic diversity of 47 A. macrostemon samples from various regions in Japan using RAD-Seq. Our analyses distinguished unique population structures, dividing the samples into three distinct groups: A, B, and C. Notably, groups A and B showed clear evidence of bulb propagation, while group C did not. Group C formed four subgroups: C1, C2, C3, and C4. Hybridization between subgroup C1 and either group A, B, or both, resulted in the emergence of subgroups C2, C3, and C4. Thus, groups A, B, and C1 are posited as the ancestral populations. Additionally, our morphological observations indicated distinct differences among these three groups. Our findings also suggest that human migration may have influenced the plant's distribution, hinting at active usage in the past that later waned, causing its current underutilized status.

Pembrolizumab: first anti-PD-1/L1-based regimen for first-line treatment of advanced esophageal cancer in Japan.

INTRODUCTION: Esophageal cancer (EC) is the ninth most common cancer in Japanese men. Esophageal squamous cell carcinoma (ESCC) is the major histological type and accounts for 90% of EC cases in Japan. The prognosis of advanced ESCC remains poor. The standard treatment for advanced ESCC was palliative chemotherapy with 5-fluorouracil plus cisplatin as first-line chemotherapy. After failure of first-line chemotherapy, taxanes were used as second-line chemotherapy. Recently, pembrolizumab monotherapy has demonstrated benefits as a second-line treatment in patients with advanced ESCC and a combined positive score of ≥10. Survival was found to be improved in patients with advanced EC who received first-line treatment with pembrolizumab plus doublet chemotherapy than in those who received doublet chemotherapy alone. AREAS COVERED: This overview of immune checkpoint inhibitors focuses on pembrolizumab in combination with chemotherapy and shares key clinical data relevant to the treatment of patients with EC in Japan. EXPERT OPINION: Pembrolizumab plus doublet chemotherapy is now an established first-line treatment for advanced EC in Japan. Recently, nivolumab plus doublet chemotherapy and nivolumab plus ipilimumab have also become first-line treatment options for patients with advanced ESCC. Further investigations are needed to identify biomarkers that would be useful for selecting candidates for these treatments.

Chirality Induction on a Coordination Capsule for Circularly Polarized Luminescence.

By utilizing a confined space inside a coordination capsule consisting of achiral components, we achieve trimeric structures composed of acetic acid and 2,3-disubstituted tartaric acid derivatives. Steric and electronic interactions between the substituents on the tartaric acid and 2,2'-bipyridyl arms of the capsule permit the transfer of the chirality of the tartaric acid to the capsule, resulting in diastereoenrichment of the host-guest complexes of up to 92 % de. The chiral templates can be washed away with diethyl ether, leaving an enantiomerically enriched capsule. The resulting capsule biases the dynamic axial chirality of a 4,4'-diacetoxybiphenyl guest carrying benzothiadiazole units, demonstrating guest-to-capsule and capsule-to-guest chirality transfer. The induced chirality on the bound guest enables it to emit circularly polarized luminescence in the NIR region, demonstrating the application of induced chirality for confined spaces for the generation of chiroptical properties.

A Thermally Activated Delayed Fluorescence Green OLED with 4500 h Lifetime and 20% External Quantum Efficiency by Optimizing the Emission Zone using a Single-Emission Spectrum Technique.

Device optimization of light-emitting diodes (LEDs) targets the most efficient conversion of electrically injected charges into emitted light. The emission zone in an LED is where charges recombine and light is emitted from. It is believed that the emission zone is strongly linked to device efficiency and lifetime. However, the emission zone size is below the optical diffraction limit, so it is difficult to measure. An accessible method based on a single emission spectrum that enables emission zone measurements with sub-second time resolution is shown. A procedure is introduced to study and control the emission zone of an LED system and correlate it with device performance. A thermally activated delayed fluorescence organic LED emission zone is experimentally measured over all luminescing current densities, while varying the device structure and while ageing. The emission zone is shown to be finely controlled by emitter doping because electron transport via the emitter is the charge-transport bottleneck of the system. Suspected quenching/degradation mechanisms are linked with the emission zone changes, device structure variation, and ageing. Using these findings, a device with an ultralong 4500 h T95 lifetime at 1000 cd m-2 with 20% external quantum efficiency is shown.

Pembrolizumab for the treatment of advanced esophageal cancer.

The prognosis of patients with advanced esophageal cancer (EC) remains poor and there are limited effective therapeutic agents for EC. Pembrolizumab monotherapy exerts clinically meaningful benefits for advanced esophageal squamous cell carcinoma patients with a combined positive score of ≥10. Additionally, pembrolizumab plus doublet chemotherapy results in a significant survival benefit for patients with advanced EC as first-line treatment compared with chemotherapy alone. We provide an overview of immune checkpoint inhibitors and present important clinical data related to treatment for EC patients. In our opinion, pembrolizumab plus chemotherapy should be the standard first-line treatment for patients with advanced EC, regardless of histology and combined positive score. Biomarker studies to identify patient populations in which immune checkpoint inhibitors are expected to show efficacy are needed.

Conceptual design of the Hybrid Ring with superconducting linac.

The Hybrid Ring with a superconducting-linac injector as a highly flexible synchrotron radiation source to enable new experimental techniques and enhance many existing ones is proposed. It is designed to be operated with the coexistence of the storage (SR) bunches characterized by the performance of the storage ring, and the single-pass (SP) bunches characterized by the performance of the superconducting linac. Unique experiments can be performed by simultaneous use of the SR and SP beams, in addition to research with various experimental techniques utilizing the versatile SR beam and research in the field of ultrafast dynamics utilizing the ultrashort pulse of the SP beam. The extendability of the Hybrid Ring will allow it to be developed into a synchrotron radiation complex.

Folding and Unfolding of Acetoxy Group-Terminated Alkyl Chains Inside a Size-Regulable Hemicarcerand.

A resorcinarene-based hemicarcerand, which consists of two cavitands covalently linked to each other by four alkyl chains, allows structural expansion and contraction by demetalation and metalation of Cu(I) cations with a size change of approximately 12 Å. This metal-mediated switching of the two states regulates the conformations of acetoxy group-terminated alkyl chains. A guest binding study reveals the encapsulation of heptyl to undecyl chains in metal-free and Cu(I)-coordinated capsules. The chemical shifts of the acetoxy groups of the bound guests are the same in the metal-free capsule, while those in the Cu(I)-coordinated one differ from each other. This indicates that the metal-free capsule regulates its size to the bound guests, while the bound guests adopt their conformations to the cavity of the Cu(I)-coordinated capsules. 1H NMR measurements and molecular mechanics calculations suggest that the bound guests have extended conformations in the metal-free capsule, while the Cu(I)-coordinated capsule forces the bound guests to adopt folded conformations. The presence of folded conformations is supported by the conformational study with structurally similar capsules and a nonsymmetric guest, allowing us to observe nuclear Overhauser effects stemming from the folded conformations of the guest in the cavity.

How Does Urban Farming Benefit Participants' Health? A Case Study of Allotments and Experience Farms in Tokyo.

In Japan, the world's most rapidly aging country, urban farming is attracting attention as an infrastructure for health activities. In Tokyo, urban residents generally participate in two types of farming programs: allotments and experience farms. The availability of regular interaction among participants distinguishes these two programs. We quantitatively examined the difference in changes in self-reported health status between participants in these two types of urban farming. We obtained retrospective cross-sectional data from questionnaire surveys of 783 urban farming participants and 1254 nonparticipants and analyzed the data using ordinal logistic regressions. As a result, compared with nonparticipants, participants in both types of urban farming reported significantly improved self-rated health (SRH) and mental health (MH). After controlling for changes in their physical activity (PA), although participants in allotments did not report significant improvement in SRH and MH, those in experience farms did, suggesting that their health improvement was not only caused by an increase in PA but also by social interaction among participants. From the perspective of health promotion, public support is needed not only for the municipality's allotments but also for the experience farms operated by the farmers themselves.

A Regulable Internal Cavity inside a Resorcinarene-Based Hemicarcerand.

Covalent organic capsules, such as carcerands and hemicarcerands, are an interesting class of molecular hosts. These container molecules have confined spaces capable of hosting small molecules, although the fact that the size of the inner cavities cannot be changed substantially limits the scope of their applications. The title covalently linked container was produced by metal-directed dimerization of a resorcinarene-based cavitand having four 2,2'-bipyridyl arms on the wide rim followed by olefin metathesis at the vertices of the resulting capsule with a second-generation Grubbs catalyst. The covalently linked bipyridyl arms permit expansion of the inner cavity by demetalation. This structural change influences the molecular recognition properties; the metal-coordinated capsule recognizes only 4,4'-diacetoxybiphenyl, whereas the metal-free counterpart can encapsulate not only 4,4'-diacetoxybiphenyl, but also 2,5-disubstituted-1,4-bis(4-acetoxyphenylethynyl)benzene, which is 9.4 Šlonger than the former guest. Molecular mechanics calculations predict that the capsule expands the internal cavity to encapsulate the long guest by unfolding the folded conformation of the alkyl chains, which demonstrates the flexible and regulable nature of the cavity. Guest competition experiments show that the preferred guest can be switched by metalation and demetalation. This external-stimuli-responsive guest exchange can be utilized for the development of functional supramolecular systems controlling the uptake, transport, and release of chemicals.

Substituent-controlled racemization of dissymmetric coordination capsules.

We report the effect of substituents (methyl, isopropyl, methoxy, and methoxyphenyl) at the 6'-position of the 2,2'-bipyridyl arms on the racemization of dissymmetric coordination capsules 1a-d. When the capsules included (R)-4,4'-diacetoxy-2,2'-benzyloxycarboxyl-biphenyl ((R)-3), the (M)-helical conformer was enriched with a diastereomeric excess (de%) of >98% for 1a, 31% for 1b, 81% for 1c and 75% for 1d. The entrapped guests in 1a, 1c and 1d can be removed by washing the solid containing the host-guest complexes with diethyl ether. The rate of racemization in THF follows the order of 1c > 1d ≫ 1a. X-ray crystal structural analysis and density functional theory calculation of model complex 4c indicate a distorted tetrahedral coordination of the Cu(i) center, and UV-vis absorption spectroscopy indicates similar coordination environments in 1c and 4c. A series of experiments demonstrates that the racemization rate depends on the dihedral angles of the bipyridyl arms, and the angles are regulated by the substituents. The methoxy and methoxyphenyl substituents in 1c and 1d enlarge the dihedral angles of the bipyridyl arms. This facilitates the access of solvent molecules to the Cu(i) centers and promotes racemization. The slower racemization of 1d can be ascribed to the steric protection of the Cu(i) centers from incoming solvent molecules by the p-methoxyphenyl group.

Correction: Substituent-controlled racemization of dissymmetric coordination capsules.

Correction for 'Substituent-controlled racemization of dissymmetric coordination capsules' by Kentaro Harada et al., Org. Biomol. Chem., 2019, DOI: 10.1039/c9ob00388f.