PI5P4K inhibitors: promising opportunities and challenges.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4K), also known as type II PIPKs or PIPKIIs, convert the lipid second messenger PI5P to PI(4,5)P. The PI5P4K family consists of three isozymes in mammals-PI5P4Kα, β, and γ-which notably utilize both GTP and ATP as phosphodonors. Unlike the other two isozymes, which can utilize both ATP and GTP, PI5P4Kβ exhibits a marked preference for GTP over ATP, acting as an intracellular GTP sensor that alters its kinase activity in response to physiological changes in GTP concentration.

An At-labeled alpha-melanocyte stimulating hormone peptide analog for targeted alpha therapy of metastatic melanoma.

Purpose: Patients who develop metastatic melanoma have a very poor prognosis, and new treatments are needed to improve the response rates. Melanocortin-1 receptor (MC1R) is a promising target for radionuclide therapy of metastatic melanoma, and alpha-melanocyte stimulating hormone (α-MSH) peptide analogs show high affinities to MC1Rs. Because targeted alpha therapy (TAT) can be a desirable treatment for metastatic melanoma, this study aimed to develop an At-labeled α-MSH peptide analog for TAT of metastatic melanoma.

Metagenomic and metatranscriptomic analyses reveal uncharted microbial constituents responsible for polyhydroxybutyrate biodegradation in coastal waters.

Polyhydroxybutyrate (PHB) has attracted attention as a representative polymer for biodegradable plastics produced by microorganisms. Since information regarding the fate of PHB released into the environment is limited, it is necessary to identify them based on metagenomic information. We estimated the PHB biodegradability in coastal water samples collected from 15 near shore sites around Japan using oxygen consumption as an indicator in laboratory-scale incubation experiments and conducted 16S rRNA gene-based microbial community profiling.

Synthesis of new functionalized bioactive S-substituted indolyl-triazoles as cytotoxic and apoptotic agents through multi-targeted kinase inhibition.

The search for new anticancer compounds is a major focus for researchers in chemistry, biology, and medicine. Cancer affects people of all ages and regions, with rising incidence rates. It does not discriminate by age or gender, making it a significant threat to humanity.

Physiological role of the FDH1 gene in methylotrophic yeast Komagataella phaffii and carbon recovery as formate during methylotrophic growth of the fdh1-deletion strain.

During methylotrophic growth of Komagataella phaffii, a large amount of carbon is lost as CO. In this study, we aimed to construct a recovery system for carbon atoms, which emit as CO along the methanol dissimilation pathway in the form of formate when using strain fdh1Δ, the deletion mutant of formate dehydrogenase gene (FDH1). Strain fdh1Δ showed a severe growth defect when using methanol as the sole carbon source.

MBGD: Microbial genome database for comparative analysis featuring enhanced functionality to characterize gene and genome functions through large-scale orthology analysis.

Microbial Genome Database for Comparative Analysis (MBGD) is a comprehensive ortholog database encompassing published complete microbial genomes. The ortholog tables in MBGD are constructed in a hierarchical manner. The top-level ortholog table is now constructed from 1,812 genus-level pan-genomes, 6,268 species-level pan-genomes, and 34,079 genomes in total.

Association of clinical knowledge with patient care ownership among resident physicians: a nationwide cross-sectional study in Japan.

Purpose: Both clinical knowledge and patient care ownership (PCO) are crucial to the provision of quality patient care and should be acquired during training. However, the association between these two concepts is under-examined. Here, we conducted a nationwide cross-sectional study to investigate the association between clinical knowledge and PCO among resident physicians in Japan.

Propagation of neuronal micronuclei regulates microglial characteristics.

Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period.

Automated xeno-free chondrogenic differentiation from human embryonic stem cells: Enhancing efficiency and ensuring high-quality mass production.

Introduction: Repairing damaged cartilage poses significant challenges, particularly in cases of congenital cartilage defects such as microtia or congenital tracheal stenosis, or as a consequence of traumatic injury, as the regenerative potential of cartilage is inherently limited. Stem cell therapy and tissue engineering offer promising approaches to overcome these limitations in cartilage healing. However, the challenge lies in the size of cartilage-containing organs, which necessitates a large quantity of cells to fill the damaged areas.

Modeling tritium release to the atmosphere during the Fukushima Daiichi Nuclear Power Plant accident and application to estimating post-accident water system transit times.

During the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on March 11, 2011, radionuclides such as tritium were released into the environment across Japan, obscuring the natural background signal of tritium in precipitation. This anthropogenic component was rapidly washed out by precipitation according to measurements in Japan. However, the impact of the accident on the natural tritium-based estimation of water system transit times in Fukushima and other prefectures in Japan remains uncertain.

Radical-cation salts of BEDT-TTF with tris-coordinated racemic dysprosium(III) and terbium(III) anions.

This paper reports the synthesis, crystal structures and conducting properties of the first BEDT-TTF radical-cation salts with symmetry tris-coordinated racemic lanthanide(III) anions. It is also the first crystallographic determination of the nine-coordinate tris(chelidonato)terbate and tris(chelidonato)dysprosate anions (chelidonic acid = clo = 4-oxo-4-pyran-2,6-dicarboxylic acid). Salt α-(BEDT-TTF)M(chelidonato)·EtOH·2HO is semimetallic for M = Tb, and semiconducting for M = Dy.

Dielectric properties depend on the crystal structure of perovskite-type RbTaO synthesized at high pressure.

We successfully synthesized perovskite-type RbTaO at 1173 K under 4 GPa. RbTaO crystalized as a cubic system (3̄ space group (SG), = 4.04108(3) Å) at 300 K in contrast to the orthorhombic perovskite-type RbNbO prepared under the same conditions.

FRET analysis of the unwrapping of nucleosomal DNA containing a sequence characteristic of the + 1 nucleosome.

Sequence-dependent mechanical properties of DNA could play essential roles in nuclear processes by affecting histone-DNA interactions. Previously, we found that the DNA entry site of the first nucleosomes from the transcription start site (+ 1 nucleosome) in budding yeast enriches AA/TT steps, but not the exit site, and the biased presence of AA/TT in the entry site was associated with the transcription levels of yeast genes. Because AA/TT is a rigid dinucleotide step, we considered that AA/TT causes DNA unwrapping.

Structure and function of a β-1,2-galactosidase from Bacteroides xylanisolvens, an intestinal bacterium.

Galactosides are major carbohydrates that are found in plant cell walls and various prebiotic oligosaccharides. Studying the detailed biochemical functions of β-galactosidases in degrading these carbohydrates is important. In particular, identifying β-galactosidases with new substrate specificities could help in the production of potentially beneficial oligosaccharides.

Discovery of bicyclic borane molecule BH.

The discovery of fullerene following the synthesis of graphene marked a paradigm shift in chemistry. Here, we report the discovery of biycycloborane, arising from the synthesis of borophane (hydrogen boride). Uniquely, this synthesis method involves a decomposition mechanism rather than traditional atom-by-atom assembly, marking an unique approach to constructing complex borane structures.

Effects of forearm rotation on wrist flexor and extensor muscle activities.

The forearm muscles coordinately control wrist motion, and their activity is affected by forearm rotation. Although forearm rotation has been implicated in the development of lateral and medial epicondylitis, its biomechanical background remains unknown. Therefore, the present study investigated the activity of wrist muscles in various forearm positions.

The preference for surprise in reinforcement learning underlies the differences in developmental changes in risk preference between autistic and neurotypical youth.

Background: Risk preference changes nonlinearly across development. Although extensive developmental research on the neurotypical (NTP) population has shown that risk preference is highest during adolescence, developmental changes in risk preference in autistic (AUT) people, who tend to prefer predictable behaviors, have not been investigated. Here, we aimed to investigate these changes and underlying computational mechanisms.

Discrepancies between subjective and objective sleep assessments revealed by in-home electroencephalography during real-world sleep.

Sleep insufficiency and sleep disorders pose serious health challenges. This study aimed to determine the potential discrepancy between subjective and objective sleep assessments, including the latter made by physicians, by analyzing a 421-participant dataset in Japan comprising multiple nights of in-home sleep electroencephalogram (EEG) data and questionnaire responses on sleep habits or subjective experiences. We employed logistic regression models to examine which subjective and objective sleep parameters physicians are paying attention to when assessing sleep insufficiency, insomnia, sleep quality, and sleep apnea.

Osmoregulation affects elimination of microplastics in fish in freshwater and marine environments.

In recent decades, microplastics (MPs) have emerged as one of the biggest environmental challenges in aquatic environments. Ingestion and toxicity of MPs in seawater (SW) and freshwater (FW) fish have been studied extensively both in field and laboratory settings. However, the basic mechanism of how fish deal with MPs in SW and FW remains unclear, although physiological conditions of fish differ significantly in the two environments.

Inverse dose protraction effects of high-LET radiation: Evidence and significance.

Biological effects of ionizing radiation vary with radiation quality, which is often expressed as the amount of energy deposited per unit length, i.e., linear energy transfer (LET).

Comparison of oncological outcomes between extended and no pelvic lymph node dissection in patients with high- or very high-risk prostate cancer: a multi-institutional study.

Background: Despite providing valuable staging and prognostic information, the therapeutic benefit of pelvic lymph node dissection (PLND) remains uncertain. We sought to assess the effect of extended PLND (ePLND) on the biochemical recurrence (BCR) of patients with National Comprehensive Cancer Net (NCCN) high- or very high-risk prostate cancer treated via robot-assisted radical prostatectomy (RARP).

Methods: We used a multi-institutional database (six centers) to assess 989 patients who underwent RARP from 2014 to 2022 with or without ePLND, among which 699 patients underwent BCR analysis.

First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).

Behavior changes to promote preconception health: a systematic review.

Background: Preconception care is expected to prevent diseases, promote health, and improve pregnancy outcomes. Although a consensus exists on the efficacy of folic acid supplementation and preconception vaccination, evidence regarding comprehensive approaches to preconception care targeting the general population remains lacking. We aimed to identify and examine preconception care programs delivered to reproductive-aged women and men to promote behavioral change.