Spiro-meroterpenoids, Syzygioblanes D-H, Isolated from Indonesian Medicinal Plant .

Syzygioblanes A-C (-), isolated from the Indonesian traditional herbal medicine (), are meroterpenoids with a spiro ring formed through a [4 + 2] cycloaddition of the flavanone desmethoxymatteucinol with cyclic sesquiterpenoids. Our ongoing phytochemical investigation of resulted in the isolation of five additional spiro-meroterpenoids, syzygioblanes D-H (-), which are hybrids of the same flavanone with eudesmane/cadinane-type sesquiterpenoids. A possible biosynthetic pathway involves enzymatic dearomative hydroxylation of desmethoxymatteucinol followed by [4 + 2] cyclization of the resulting diene with a cyclic sesquiterpene containing an exocyclic methylene to form the unique spiro ring in the syzygioblane molecule.

Feasibility assessment of Japan's fertilizer reduction target: A meta-analysis and its implications for nitrogen waste.

Reducing synthetic nitrogen fertilizer (SNF) use is critical for mitigating environmental nitrogen (N) pollution caused by excessive reactive nitrogen and lowering the cost of chemical N fertilizer inputs in agricultural management. In response, Japan has set a national target to reduce chemical fertilizer inputs, with a goal of 30% reduction in SNF use. To assess the feasibility of this target, we collected ca.

Inhibition sensitivity of in vitro firefly bioluminescence quantum yields to Zn and Cd concentrations in aqueous solutions.

To elucidate the inhibition effects of Zn and Cd on the luciferin-luciferase reaction, we performed quantitative measurements of quantum yields and spectral shapes for in vitro firefly bioluminescence in aqueous solutions containing ZnSO, ZnCl, CdSO, and CdCl at different concentrations. Particular care was taken toward the equilibrium between metal ions and enzyme proteins, anion difference, solubility, and uncertainty evaluation. The bioluminescence quantum yields decreased almost linearly to the concentration of Zn and Cd below 0.

Inventing Novel Protein Folds.

The vastness of unexplored protein fold universe remains a significant question. Through systematic de novo design of proteins with novel αβ-folds, we demonstrated that nature has only explored a tiny portion of the possible folds. Numerous possible protein folds are still untouched by nature.

Gold(I) Catalysis in Alkyne-Alkene Reactions: A Systematic Exploration through Molecular Electrostatic Potential Analysis.

Gold catalysis enables selective chemical transformations with catalytic activity tunable through ligand selection. This study uses the density functional theory (DFT) to explore the impact of phosphine ligands (PR) on gold(I)-catalyzed alkyne-alkene cyclobutene formation. We analyze the following key steps: (i) PR-Au complexation, (ii) alkyne binding, (iii) alkene binding, (iv) C-C coupling transition state, (v) cyclobutene formation transition state, and (vi) cyclobutene dissociation.

Quality of life and work productivity and activity impairment among online survey respondents with migraine across a range of headache frequency.

Objective: This study aimed to describe the migraine burden and healthcare utilization in the context of headache frequency using nationwide claims data linked to online survey data previously collected in Japan.

Background: It has been shown that increase in headache frequency can impose greater impact on individuals' daily and social functioning, but migraine burden in those with low-frequency headaches remains largely unknown in Japan.

Methods: This , observational study reported on 674 respondents who were working individuals and their family members aged 19-74 years, responded to an online questionnaire (response rate: 14.

Serum perampanel levels in patients with seizures are not affected by hemodialysis.

Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis.

Water vapor effect on the physico-geometrical reaction pathway and kinetics of the multistep thermal dehydration of calcium chloride dihydrate.

This study investigated how water vapor influences the reaction pathway and kinetics of the multistep thermal dehydration of inorganic hydrates, focusing on CaCl·2HO (CC-DH) transforming into its anhydride (CC-AH) an intermediate of its monohydrate (CC-MH). In the presence of atmospheric water vapor, the thermal dehydration of CC-DH stoichiometrically proceeded through two distinct steps, resulting in the formation of CC-AH CC-MH under isothermal conditions and linear nonisothermal conditions at a lower heating rate (). Irrespective of atmospheric water vapor pressure ((HO)), these reaction steps were kinetically characterized by a physico-geometrical consecutive process involving the surface reaction and phase boundary-controlled reaction, which was accompanied by three-dimensional shrinkage of the reaction interface.

Impact of comprehensive geriatric assessment on treatment strategies and complications in older adults with colorectal cancer considering surgery.

Background And Objectives: This study aimed to assess the effectiveness of Comprehensive Geriatric Assessment (CGA) in customizing care for elderly cancer patients, specifically focusing on colorectal cancer. The research compared treatment strategies and outcomes in older adults considered for surgery before and after the initiation of a Geriatric Oncology Service (GOS).

Methods: Conducting a comparative study, two cohorts of consecutive colorectal cancer patients aged 75 or older were examined: the control group (n = 156) and the GOS group (n = 158).

Atomistic Simulation of Hf-Pyridyl Amido-Catalyzed Chain Transfer Alkene Polymerization Reaction and Its Machine Learning for Extraction of Essential Descriptors: Effect of Microscopic Steric Hindrance on the Monomer Insertion Process.

The microscopic effects of each substituent of the Hf catalyst and the growing polymer on the monomer insertion process were investigated for Hf-pyridyl amido-catalyzed coordinative chain transfer polymerization using the Red Moon method. Since the Hf catalyst has two reaction sites, - and -sites, we separately applied the appropriate analysis methods to each one, revealing that the naphthalene ring influenced monomer insertion at the -one, while the -Pr group and the hexyl group of the adjacent 1-octene unit did the -one. It was interesting to find that the hexyl group of the 1-octene-inserted catalyst (oHfCat) pushes the naphthalene ring toward the -site and narrows the space at the -site, thus indirectly creating a steric hindrance to -insertions.

Levels and spatial profile of per- and polyfluoroalkyl substances in edible shrimp products from Japan and neighboring countries; a potential source of dietary exposure to humans.

Exposure to per- and polyfluoroalkyl substances (PFAS) is of great concern for human health because of their persistence and potentially adverse effects. Dietary intake, particularly through aquatic products, is a significant route of human exposure to PFAS. We analyzed perfluoroalkyl sulfonic acid (PFSA with carbon numbers from 6 to 8 and 10 (C-C, C)) and perfluorooctanesulfonamide (FOSA), and perfluoroalkyl carboxylic acid (PFCA with carbon numbers from 6 to 15 (C-C)) in 30 retail packs of edible shrimps, which included seven species from eight coastal areas of Japan and neighboring countries.

A study to investigate the prevalence of headache disorders and migraine conducted using medical claims data and linked results from online surveys: post-hoc analysis of other headache disorders.

Background: Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine.

Methods: Anonymized surveys coupled with medical claims data from individuals 19-74 years old were obtained from DeSC Healthcare Inc.

Cyclic Sesquiterpene-Flavanone [4+2] Hybrids, Syzygioblanes A-C, Found in an Indonesian Traditional Medicine, "Jampu Salo" ().

A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally as "Jampu Salo" was collected on Sulawesi Island, Indonesia. It was identified as (C. B.

Characteristics of patients who seek medical attention for headache and those who do not: cross-sectional survey and linked medical claims data analysis in Japan.

Objective: To describe the characteristics of patients who sought medical attention for headache and those who did not.

Design: This observational study used a cross-sectional online survey and linked medical claims data.

Setting: Data from an online self-administered questionnaire survey conducted in November 2020 as well as linked medical claims data spanning December 2017 and November 2020 were provided by DeSC Healthcare Inc.

The physico-geometrical reaction pathway and kinetics of multistep thermal dehydration of calcium chloride dihydrate in a dry nitrogen stream.

Several inorganic hydrates exhibit reversible reactions of thermal dehydration and rehydration, which is potentially applicable to thermochemical energy storage. Detailed kinetic information on both forward and reverse reactions is essential for refining energy storage systems. In this study, factors determining the reaction pathway and kinetics of the multistep thermal dehydration of inorganic hydrates to form anhydride intermediate hydrates were investigated as exemplified by the thermal dehydration of CaCl·2HO (CC-DH) in a stream of dry N.

Experimental and Theoretical Study for Core Excitation of Firefly Luciferin in Carbon K-Edge Spectra.

Carbon (C) K-edge X-ray absorption spectra for firefly luciferin were measured and assigned using time-dependent density functional theoretical calculations for luciferin anion and dianion to elucidate the effect of hydroxy-group deprotonation. It was found that the C K-edge spectra for luciferin had four characteristic peaks. The effect of deprotonation of the hydroxy group appears in the energy difference of the first and second peaks of these spectra.

Design of complicated all-α protein structures.

A wide range of de novo protein structure designs have been achieved, but the complexity of naturally occurring protein structures is still far beyond these designs. Here, to expand the diversity and complexity of de novo designed protein structures, we sought to develop a method for designing 'difficult-to-describe' α-helical protein structures composed of irregularly aligned α-helices like globins. Backbone structure libraries consisting of a myriad of α-helical structures with five or six helices were generated by combining 18 helix-loop-helix motifs and canonical α-helices, and five distinct topologies were selected for de novo design.

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.

Aims: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response.

Methods: This placebo-controlled, randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17-item total score ≥ 14; historical inadequate response to 1-3 ADTs) with inadequate response to 8-week single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo.

Efflorescence kinetics of sodium carbonate decahydrate: a universal description as a function of temperature, degree of reaction, and water vapor pressure.

The efflorescence of sodium carbonate decahydrate (SC-DH) required to form its monohydrate (SC-MH) was systematically studied under isothermal and linear nonisothermal conditions at different atmospheric water vapor pressures ((HO)) using a humidity-controlled thermogravimetry instrument equipped with a cooling circulator. The universal kinetic description at various temperatures () and (HO) values was evaluated using the extended kinetic equation with an accommodation function (AF) comprising (HO) and the equilibrium pressure of the reaction (()). By optimizing two exponents in the AF, all kinetic data were universally described in terms of the isoconversional kinetic relationship examined at individual degrees of reaction ().

Effects of Fremanezumab on Medication Overuse in Japanese Chronic Migraine Patients: Post Hoc Analysis of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Chronic migraine (CM) patients commonly take acute headache medications, often resulting in medication overuse (MO). This post hoc analysis evaluated the efficacy of fremanezumab in CM patients from Japan with and without MO, which is not yet established.

Methods: A multicenter, double-blind, parallel-group, phase 2b/3 trial randomized patients (1:1:1) to monthly fremanezumab via subcutaneous injection (initial dose: 675 mg, second/third doses: 225 mg), quarterly fremanezumab (initial dose: 675 mg, second/third doses: placebo), or placebo for 3 months.

Atomistic Chemical Elucidation of the Higher-Rate Reaction Mechanism in Hf-Pyridyl Amido-Catalyzed Copolymerization of Ethene and 1-Octene: Application of Red Moon Simulation with Polymer Propagation Diagrams.

The Hf-pyridyl amido complex ((pyridylamido)Hf(IV)) is a cationic catalyst activated by ion-pairing with auxiliary catalyst B(CF) to show high activity for α-olefin polymerization. Previously, it was experimentally observed that the consumption rate of 1-octene in the 1-octene/ethene copolymerization is 3-fold compared to the 1-octene homopolymerization in coordinative chain transfer polymerization using the catalyst HfCat-B(CF) ion pair (IP) and the chain transfer agent (CTA) ZnEt. In the present study, we have performed atomistic chemical simulations of the IP-catalyzed homopolymerization of 1-octene and copolymerization of 1-octene and ethene on the basis of the Red Moon (RM) methodology.

Improved quality of life with fremanezumab in Japanese and Korean patients with episodic and chronic migraine: Results of two multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trials.

Objective: To evaluate quality of life (QoL) endpoints from two 12-week trials investigating fremanezumab efficacy and safety in Japanese/Korean patients with chronic (CM) or episodic (EM) migraine.

Background: Migraine is a leading cause of disability and affects QoL considerably, interfering with work and daily activities, social and family life, and emotional wellbeing.

Methods: This planned exploratory analysis used data from two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which Migraine-Specific QoL (MSQoL; Role Function-Restrictive [RR], Role Function-Preventive [RP], and Emotional Function [EF] domains) scores and Patient Global Impression of Change (PGIC) scores were pre-specified QoL outcomes in individuals receiving monthly or quarterly fremanezumab or placebo.

Design of allosteric sites into rotary motor V-ATPase by restoring lost function of pseudo-active sites.

Allostery produces concerted functions of protein complexes by orchestrating the cooperative work between the constituent subunits. Here we describe an approach to create artificial allosteric sites in protein complexes. Certain protein complexes contain subunits with pseudo-active sites, which are believed to have lost functions during evolution.

Exploration of novel αβ-protein folds through de novo design.

A fundamental question in protein evolution is whether nature has exhaustively sampled nearly all possible protein folds throughout evolution, or whether a large fraction of the possible folds remains unexplored. To address this question, we defined a set of rules for β-sheet topology to predict novel αβ-folds and carried out a systematic de novo protein design exploration of the novel αβ-folds predicted by the rules. The designs for all eight of the predicted novel αβ-folds with a four-stranded β-sheet, including a knot-forming one, folded into structures close to the design models.