[Sixth wave of COVID-19 pandemic: Epidemiological survey in children].

Objectives　At the beginning of the COVID-19 pandemic, the number of infected children was lower than that of adults. Most cases were transmitted in the family, asymptomatic, and severe cases were rare. In the sixth wave in Japan the number of infected children increased sharply after the Omicron variant had been replaced in December 2021, which had a substantial influence in maintaining social and medical functions. Furthermore, few reports on child death in the country have raised concerns among parents. However, no literature has elucidated the epidemiological characteristics of the Omicron variant in children. In this study, we aimed to clarify them during the sixth wave in Japan.Methods　We analyzed the data of 28,086 COVID-19-infected patients those were registered in the Yamashirokita Public Health Center between January 15, 2022 and May 31, 2022. The cumulative incidence and hospitalization rate were compared between the age groups <15 and those >15 years based on the databases compiled by our public health center and the Kyoto prefecture government. In addition, we analyzed the background, length of hospitalization, and clinical symptoms of 24 patients based on active epidemiological investigation, health observations, and discharge reports submitted from medical facilities.Results　Of the 52,897 residents <15 years (pediatric population is 12.3%), 15.1% (7,980 cases) were infected, and children accounted for 28.4% of all-age infected patients. Among them, 24 were hospitalized (0.3% of children with COVID-19, 0.04% of the child population). Conversely, of the 377,093 residents aged ≥15 years, 5.3% (20,106 patients) were infected. Among them, 1,088 were hospitalized (5.4% of COVID-19 patients, 0.28% of the adult population). For 24 hospitalized children, 22 (91.6%) had mild cases and 2 (8.3%) had moderate cases, and no severe case was noted based on the criteria of severity in Japan's COVID-19 medical care guidelines. Two patients (8.3%) were hospitalized for treatment of other diseases. The median of hospital stay was 3.5 days, and 20 patients (83.3%) were discharged home during the recuperation period.Conclusions　The cumulative incidence of children with COVID-19 in the sixth wave was 15.1%, approximately three times higher than that of the older patients; however, no severe case was observed in children.

Source of Rate Acceleration for Carbocation Cyclization in Biomimetic Supramolecular Cages.

The results of quantum chemical and molecular dynamics calculations reveal that polyanionic gallium-based cages accelerate cyclization reactions of pentadienyl alcohols as a result of substrate cage interactions, preferential binding of reactive conformations of substrate/H3O+ pairs, and increased substrate basicity. However, the increase in basicity dominates. Experimental structure-activity relationship studies in which the metal vertices and overall charge of the cage are varied confirm the model derived via calculations.

Chemoselective and Site-Selective Reductions Catalyzed by a Supramolecular Host and a Pyridine-Borane Cofactor.

Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramolecular host-promoted synthesis of small molecules, applications of this reactivity to chemoselective and site-selective modification of complex biomolecules remain virtually unexplored. We report here a supramolecular system where coencapsulation of pyridine-borane with a variety of molecules including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same molecule is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, we then applied this supramolecular reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.

OTC drug advertising in Japan: the role of need for cognition and celebrity endorser credibility.

This research explores how the level of consumers' need for cognition (NFC) is associated with celebrity endorser credibility and examines its effects on advertising-related attitudes. A 3 (endorser types: actor/actress, athlete, TV personality/talent) × 2 (endorser's gender) factorial experiment with 435 Japanese consumers was conducted. Concerning Japanese OTC drug advertising, lower NFC individuals perceived celebrity endorsers as more credible in comparison to higher NFC individuals. The main effects of NFC and endorser type on endorser credibility existed; however, no interaction between the two variables was found. The endorser type had an influence on attitudes toward ads and the advertised brand.

Supramolecular Host-Selective Activation of Iodoarenes by Encapsulated Organometallics.

Supramolecular hosts offer defined microenvironments that facilitate selective host-guest interactions, enabling reactivity that would otherwise be challenging in bulk solution. While impressive rate enhancements and selectivities have been reported, similar reactivity can often be accessed through modifications of reaction conditions even in the absence of the host. We report here an oxidative addition of aryl halides across the metal centers in Cu(I) and Pd(II) organometallics that is assisted by the presence of a supramolecular host, realized via electrostatic stabilization and increased local substrate concentrations. When reaction conditions were screened to assess background reactivity, alternative reactivity (typically decomposition) resulted, indicating that encapsulation led to host-selective reaction trajectories.

Deconvoluting the Role of Charge in a Supramolecular Catalyst.

We have demonstrated that the microenvironment of a highly anionic supramolecular catalyst can mimic the active sites of enzymes and impart rate accelerations of a million-fold or more. However, these microenvironments can be challenging to study, especially in the context of understanding which specific features of the catalyst are responsible for its high performance. We report here the development of an experimental mechanistic probe consisting of two isostructural catalysts. When examined in parallel transformations, the behavior of these catalysts provides insight relevant to the importance of anionic host charge on reactivity. These two catalysts exhibit similar host-substrate interactions, but feature a significant difference in overall anionic charge (12- and 8-). Within these systems, we compare the effect of constrictive binding in a net neutral aza-Cope rearrangement. We then demonstrate how the magnitude of anionic host charge has an exceptional influence on the reaction rates for a Nazarov cyclization, evidenced by an impressive 680-fold change in reaction rate as a consequence of a 33% reduction in catalyst charge.

Mechanism of Acylative Oxidation-Reduction-Condensation Reactions Using Benzoisothiazolones as Oxidant and Triethylphosphite as Stoichiometric Reductant.

We previously described a new organocatalytic oxidation-reduction-condensation for amide/peptide construction. The reaction system relies on triethylphosphite as the stoichiometric reductant and organocatalytic benzoisothiazolone/O2 in air as the oxidant. The reaction was assumed to generate catalytic quantities of S-acylthiosalicylamides as electrophiles, which are rapidly intercepted by amine reactants to generate amides/peptides and o-mercaptobenzamides. The latter are then gently reoxidized to the benzoisothiazolones under Cu-catalyzed aerobic conditions to complete the catalytic cycle. To gain a mechanistic understanding, we describe herein our studies of the stoichiometric generation of S-acylthiosalicylamides under oxidation-reduction-condensation conditions from a variety of benzoisothiazolones and carboxylic acids using triethylphosphite as the terminal reductant. These studies have revealed the presence of more than one reaction pathway when benzoisothiazolones react with triethylphosphite (including a rapid, direct deoxygenation of certain classes of benzoisothiazolones by triethylphosphite) and allow the identification of optimal reaction characteristics (benzoisothiazolone structure and solvent) for the generation of thioesters. These explorations will inform our efforts to develop highly effective and robust organocatalytic oxidation-reduction-condensation reactions that are based on the benzoisothiazolone and related motifs.

Tumor Immune Cell Targeting Chimeras (TICTACs) For Targeted Depletion of Macrophage-Associated Checkpoint Receptors.

Immune cells in the tumor microenvironment are not only powerful regulators of immunosuppression and tumorigenesis, but also represent a dominant cell type, with tumor-associated macrophages (TAMs) comprising up to 50% of total cell mass in solid tumors. Immunotherapies such as immune checkpoint inhibitors (ICIs) derive their efficacy from this cancer-immune cell interface, however, immune-related adverse events resulting from systemic blockade remain a significant challenge. To address this need for potent, yet highly tumor-specific immunotherapies, we developed Tumor-Immune Cell Targeting Chimeras (TICTACs), antibody conjugates that are capable of selectively depleting immune checkpoint receptors such as SIRPa from the surface of TAMs. These chimeric molecules consist of a synthetic glycan ligand that binds the C-type lectin CD206, a well-established TAM marker, conjugated to a non-blocking antibody that binds but does not inhibit the checkpoint receptor. By engaging CD206, which constitutively recycles between the plasma membrane and early endosomes, TICTACs facilitate robust removal of the checkpoint receptors from the surface of CD206high macrophages, while having no effect on CD206low macrophages. By decoupling antibody selectivity from its blocking function, we present a new paradigm for developing highly tumor-specific immunotherapies.