Pharmacokinetics, Pharmacodynamics, and Safety of Evocalcet (KHK7580), a Novel Calcimimetic Agent: An Open-Label, Single- and Multiple-Dose, Phase I Trial in Healthy Chinese Subjects.

Purpose: This study explored the pharmacokinetics (PK), pharmacodynamics (PD), and safety of evocalcet (KHK7580), a new calcimimetic agent, in healthy Chinese subjects following single and multiple doses.

Methods: This was a single-center, open-label phase I trial conducted in China. The study started from the single-dose cohorts (1, 3, 6, 12 mg evocalcet, step-by-step administration) and proceeded to the multiple-dose cohort (6 mg evocalcet once daily for eight days).

Comparison of the Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Patients on Hemodialysis with Secondary Hyperparathyroidism.

Introduction: Evocalcet is an oral calcimimetic agent with proven efficacy and safety in treating secondary hyperparathyroidism (SHPT) in Japanese patients on dialysis.

Methods: This randomized, double-blind, intrapatient dose-adjustment, parallel-group, international multicenter study compared the efficacy and safety of evocalcet versus cinacalcet for 52 weeks in East Asian hemodialysis patients with SHPT.

Results: In total, 203 and 200 patients were randomized to receive evocalcet or cinacalcet, respectively (overall, 70.

Deep learning driven de novo drug design based on gastric proton pump structures.

Existing drugs often suffer in their effectiveness due to detrimental side effects, low binding affinity or pharmacokinetic problems. This may be overcome by the development of distinct compounds. Here, we exploit the rich structural basis of drug-bound gastric proton pump to develop compounds with strong inhibitory potency, employing a combinatorial approach utilizing deep generative models for de novo drug design with organic synthesis and cryo-EM structural analysis.

First Report of the Physiological Race (XXIV) of (Coffee Leaf Rust) in Hawaii.

Hawaii's coffee industry, produced commercially on six islands by over 1,470 growers on ~10,000 acres, is conservatively valued at $100M per year (USDA NASS 2023). Until late October 2020, Hawaii was the only major coffee producing region of the world that was free of Coffee Leaf Rust (CLR). Growers are currently facing their most formidable production challenge with the arrival of Berk.

Diet quality and depressive symptoms among workers.

Background & Aim: It is not clear whether diet quality influences mental health. We prospectively investigated the association of adherence to the Japanese dietary guidelines with depressive symptoms in a Japanese working population.

Methods: Participants were 909 workers (aged 19-68 years) without depressive symptoms at baseline who completed both baseline and 3-year follow-up surveys.

[The Neural Mechanisms of Joint Attention].

Joint attention behaviors involve sharing attention with others to an object or event by means of eye-gazing or pointing, which form the common basis for communication. There are two types of these behaviors: responding to joint attention (RJA) and initiating joint attention (IJA). RJA is the ability to follow the gaze of others, suggesting reception of a social signal from others; IJA is the ability to voluntarily direct the attention of others, to share the experience of an object or event, suggesting transmission of a social signal to others.

Dysconnectivity of the Agency Network in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood.

Publisher Correction: Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.

In the version of this article originally published, the accession codes listed in the data availability section were incorrect and the section was incomplete. The text for this section should have read "The genome assembly and gene annotation have been deposited in the NCBI database under accession number QVOL00000000, BioProject number PRJNA483885 and BioSample number SAMN09753102. The data can also be downloaded from the following link: http://www.

Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.

Modern sugarcanes are polyploid interspecific hybrids, combining high sugar content from Saccharum officinarum with hardiness, disease resistance and ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85-441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous groups of 4 members each, bearing 35,525 genes with alleles defined.

Transcriptomic analysis of transgressive segregants revealed the central role of photosynthetic capacity and efficiency in biomass accumulation in sugarcane.

Sugarcane is among the most efficient crops in converting solar energy into chemical energy. However, due to its complex genome structure and inheritance, the genetic and molecular basis of biomass yield in sugarcane is still largely unknown. We created an F2 segregating population by crossing S.

Cell wall metabolism and hexose allocation contribute to biomass accumulation in high yielding extreme segregants of a Saccharum interspecific F2 population.

Background: Sugarcane is an emerging dual-purpose biofuel crop for energy and sugar production, owing to its rapid growth rate, high sucrose storage in the stems, and high lignocellulosic yield. It has the highest biomass production reaching 1.9 billion tonnes in 2014 worldwide.

Electrophysiological assessment of driving pleasure and difficulty using a task-irrelevant probe technique.

The amplitude of event-related brain potentials (ERPs) elicited by task-irrelevant auditory probes decreases when more attentional resources are allocated to a visual task. This task-irrelevant probe technique is considered to be useful in assessing the degree of interest in a visual task, as well as task difficulty. The present study examined the amplitude of the N1 and P2 components elicited by task-irrelevant auditory probes during a driving task in a simulated environment.

Identification of 3-methylbutanoyl glycosides in green Coffea arabica beans as causative determinants for the quality of coffee flavors.

The quality of coffee green beans is generally evaluated by the sensory cupping test, rather than by chemical compound-based criteria. In this study, we examined the relationship between metabolites and cupping scores for 36 varieties of beans, using a nontargeted LC-MS-based metabolic profiling technique. The cupping score was precisely predicted with the metabolic information measured using LC-MS.

Sensory synergy as environmental input integration.

The development of a method to feed proper environmental inputs back to the central nervous system (CNS) remains one of the challenges in achieving natural movement when part of the body is replaced with an artificial device. Muscle synergies are widely accepted as a biologically plausible interpretation of the neural dynamics between the CNS and the muscular system. Yet the sensorineural dynamics of environmental feedback to the CNS has not been investigated in detail.

Identification and characterization of receptors for ion transport peptide (ITP) and ITP-like (ITPL) in the silkworm Bombyx mori.

Ion transport peptide (ITP) and its alternatively spliced variant, ITP-like (ITPL), are insect peptides that belong to the crustacean hyperglycemic hormone family. These peptides modulate the homeostatic mechanisms for regulating energy metabolism, molting, and reproduction and are specifically conserved in ecdysozoans. Many of the details of the molecular mechanisms by which crustacean hyperglycemic hormone family peptides exert pleiotropy remain to be elucidated, including characterization of their receptors.

The coffee genome provides insight into the convergent evolution of caffeine biosynthesis.

Coffee is a valuable beverage crop due to its characteristic flavor, aroma, and the stimulating effects of caffeine. We generated a high-quality draft genome of the species Coffea canephora, which displays a conserved chromosomal gene order among asterid angiosperms. Although it shows no sign of the whole-genome triplication identified in Solanaceae species such as tomato, the genome includes several species-specific gene family expansions, among them N-methyltransferases (NMTs) involved in caffeine production, defense-related genes, and alkaloid and flavonoid enzymes involved in secondary compound synthesis.

Direct chemiluminescent enzyme immunoassay for atrial natriuretic peptide in mammalian plasma using a PEGylated antibody.

Atrial natriuretic peptide (ANP) is a peptide hormone that is synthesized and secreted by cardiac tissues and plays a pivotal role in maintaining cardiovascular homeostasis. Clinically, ANP is used as a marker of cardiovascular diseases, including heart failure. Although multiple ANP assays are currently available, a more sensitive assay is required for the direct measurement of plasma ANP where there is limited plasma availability, especially in mouse experiments.

Uptake of cesium and strontium ions by artificially altered phlogopite.

Potassium (K(+)) phlogopite was transformed to a vermiculite-like mineral through a topotactic reaction under acidic conditions (pH 2) followed by hydrothermal treatment with Na(+), Mg(2+), Ca(2+), and Al(3+) cations. The resulting Na(+)-, Mg(2+)-, Ca(2+)-, and Al(3+)-altered phlogopites (Phl) denoted as Na-Phl, Mg-Phl, Ca-Phl, and Al-Phl, respectively. Na-Phl, Mg-Phl, and Ca-Phl all exhibited the same high adsorption capacity as natural vermiculite and the absorption of Cs(+) and Sr(2+) ions on these materials followed the Langmuir model.

A new powered orthosis with hip and ankle linkage for paraplegics walking.

Several types of hip-knee-ankle-foot orthotic systems have been proposed for paraplegic walking during these decades. Hip and ankle linked orthosis (HALO) is compact one in those orthoses, which seeks to achieve a smoother-movement and user-easiness on its don/doff in paraplegic walking. The idea of HALO is to link two ankle joints with medial single joint via wires so that the orthosis keeps both feet always parallel to the floor while walking and assist the swinging of the leg.

High-throughput metabolic profiling of diverse green Coffea arabica beans identified tryptophan as a universal discrimination factor for immature beans.

The maturity of green coffee beans is the most influential determinant of the quality and flavor of the resultant coffee beverage. However, the chemical compounds that can be used to discriminate the maturity of the beans remain uncharacterized. We herein analyzed four distinct stages of maturity (immature, semi-mature, mature and overripe) of nine different varieties of green Coffea arabica beans hand-harvested from a single experimental field in Hawaii.

Urinary excretion levels of water-soluble vitamins in pregnant and lactating women in Japan.

Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk, n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo, n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey.

Hexarelin treatment in male ghrelin knockout mice after myocardial infarction.

Both ghrelin and the synthetic analog hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin-knockout mice and to compare the effects of hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial infarction.

Simulation of human walking with powered orthosis for designing practical assistive device.

To design a powered assistive orthosis for human walking, we have simulated walking motion with an orthosis. The model dynamics of the coupled human-orthosis is represented by a 10-rigid-link system. In this model there exist rotational joints at lumbar, both thighs and both legs for orthosis, and each joints are controlled by a couple of central pattern generators (CPG) which imitates neuronal system in the spinal cord of mammals.

Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario.

Changes occurring in phenolic compounds and purine alkaloids, during the growth of seeds of cacao (Theobroma cacao) cv. Trinitario, were investigated using HPLC-MS/MS. Extracts of seeds with a fresh weight of 125, 700, 1550, and 2050 mg (stages 1-4, respectively) were analyzed.

Effects of starvation on brain short neuropeptide F-1, -2, and -3 levels and short neuropeptide F receptor expression levels of the silkworm, Bombyx mori.

In our previous report, we demonstrated the possibility that various regulatory neuropeptides influence feeding behavior in the silkworm, Bombyx mori. Among these feeding-related neuropeptides, short neuropeptide F (sNPF) exhibited feeding-accelerating activity when injected into B. mori larvae.