This study assessed the feasibility of unconstrained deep-learning-based sleep stage classification using cardiorespiratory and body movement activities derived from piezoelectric sensors installed under a bed mattress. Heart and respiratory rates and their respective variabilities, cardiorespiratory coupling index, and body movement were simultaneously acquired through polysomnography (PSG) for 106 untreated participants with suspected sleep apnea. We used a bidirectional long short-term memory network to predict the five sleep stages using five different input feature combinations. The best performance was achieved with a model comprising six parameters, including cardiorespiratory variability features, with a balanced accuracy of 0.70 ± 0.05, Cohen's κ of 0.40 ± 0.11, and an F1 score of 0.63 ± 0.08. Deming regression and Bland-Altman analyses of the six major sleep parameters estimated by the model and those determined by PSG showed significant correlations (r = 0.426-0.781) with a low bias. These results demonstrate the effectiveness of the proposed approach and its potential to expand opportunities for in-home sleep monitoring.

Adherent eukaryotic cells typically exhibit amoeboid locomotion through actin polymerization and bleb-driven mechanisms. However, testate amoebae, which enclose their bodies within a shell, exhibit variation in these locomotion types. This study focused on Arcella, a representative testate amoeba that pulls its shell using multiple pseudopods extending from a single aperture on the ventral side. Arcella may be found in peatlands and freshwater, where it adapts its movement to various substrates. We characterized its movement on glass as well as hard, and soft gel substrates through detailed observation. The results indicated a higher randomness in motion on the soft gel, which was influenced by the pseudopodial elongation direction. Additionally, we evaluated the relationship between movement direction and traction stress. The dipole moment of the traction stress field determined the axis of motion, whereas quadrupole moments were correlated with forward and lateral movements. Although some relationships between multipole moments and velocity were shared with other cells, Arcella exhibited unique characteristics in its movement mechanism, which likely occurred due to its use of multiple pseudopods alongside its shell.

M-COPA (1), which contains diene and 3-picolylamine moieties in its side chain and seven stereogenic centers in a multisubstituted octalin skeleton, strongly inhibits the growth of several cancer cell lines. Expecting the improvement of conformational flexibility of basic and coordinating 3-pyridylmethylamino group on M-COPA and its physical properties, we efficiently synthesized its amine analogs by replacing its amide group with an amino group through the Weinreb amide-type Horner-Wadsworth-Emmons reaction. The cytotoxic properties of 1 and its analogs were evaluated against NCI-H226, a lung cancer cell line, HeLa, a cervical cancer cell line, and GIST-T1, a gastrointestinal stromal tumor cell line. The evaluation results indicated that the structural alteration from amide moiety to amine moiety lowered the pharmacological activity but remained strong cytotoxicity.

Tetrodotoxin (TTX), the pufferfish toxin, has the potential to cause fatal food poisoning because of its potent voltage-gated sodium channel (Na) blocking activity. 4-epiTTX, 11-norTTX-6(S)-ol, and 11-oxoTTX are the major TTX analogues found in marine animals; thus, their chemical properties and biological activities should be determined. In this study, these three TTX analogues were purified to a high level (purity >97%) from pufferfish and newts. The ratios of the hemilactal to the 10,7-lactone forms were determined using H NMR, and C NMR data were also obtained. 4-epiTTX underwent considerable transformation to TTX in physiological conditions. The Na blocking activity of these analogues was evaluated by whole-cell patch-clamp recording using a human Na1.2, colorimetric cell-based assay and mouse bioassay. The toxicity equivalency factors (TEFs setting TTX 1) of the three analogues were estimated; 4-epiTTX (0.06), 11-norTTX-6(S)-ol (0.02), and 11-oxoTTX (1.2) using patch-clamp recording, and 11-norTTX-6(S)-ol (0.50) and 11-oxoTTX (0.42) using the mouse bioassay. These data confirmed the low Na blocking activity of 4-epiTTX and high activity of 11-oxoTTX.

Renal counterbalance, involving compensatory hypertrophy of the healthy kidney and atrophy of the injured one, remains incompletely understood, particularly at the glomerular level. In this study, we employed NEP25 mice, which selectively express human CD25 in podocytes, enabling precise induction of unilateral podocyte injury through the administration of LMB2, a CD25-targeted immunotoxin. Using a two-kidney, one-nephropathy (2K1N) model, we demonstrated that asymmetric changes in renal blood flow and proteinuria, with histological and transcriptomic analyses uncovering distinct pathological and molecular features between the injured and contralateral healthy kidneys. Notably, an imbalance in intrarenal angiotensin (Ang) II levels was observed, and angiotensin-converting enzyme inhibition ameliorated the glomerular damage and restored perfusion. These findings indicate that local Ang II dysregulation is a key factor in renal counterbalance. Our study provides the first glomerulopathy-based experimental platform to dissect asymmetric renal adaptation, offering fundamental insight into the homeostatic mechanisms of renal function in health and disease.

The organization and dynamics of chromatin are critical for genome functions such as transcription and DNA replication/repair. Historically, chromatin was assumed to fold into the 30-nm fiber and progressively arrange into larger helical structures, as described in the textbook model. However, over the past 15 years, extensive evidence including our studies has dramatically transformed the view of chromatin from a static, regular structure to one that is more variable and dynamic. In higher eukaryotic cells, chromatin forms condensed yet liquid-like domains, which appear to be the basic unit of chromatin structure, replacing the 30-nm fiber. These domains maintain proper accessibility, ensuring the regulation of DNA reaction processes. During mitosis, these domains assemble to form more gel-like mitotic chromosomes, which are further constrained by condensins and other factors. Based on the available evidence, I discuss the physical properties of chromatin in live cells, emphasizing its viscoelastic nature-balancing local fluidity with global stability to support genome functions.

Aegilops tauschii Coss., a progenitor of bread wheat, is an important wild genetic resource for breeding. The species comprises three genetically defined lineages (TauL1, TauL2, and TauL3), each displaying valuable phenotypes in agronomic traits, including spike shape. In the present work, we studied the relationship between population structure and spike shape variation patterns using a collection of 249 accessions. f-statistics-based ancestry profiling confirmed the previously identified lineages and revealed a genetic component derived from TauL3 in the genomes of some southern Caspian and Transcaucasus TauL1 and TauL2 accessions. Spike shape variation patterns were analyzed using a convolutional neural network-based approach, trained on green and dry spike image datasets. This analysis showed that spike shape diversity is structured according to lineages and demonstrated the potential to distinguish the lineages based on spike shape. The implications of these findings for the origins of common wheat and the intraspecific taxonomy of Ae. tauschii are discussed.

Why and how do we age? This physiological phenomenon that we all experience remains a great mystery, largely unexplained even in this age of scientific and technological progress. Aging is a significant risk factor for numerous diseases, including cancer. However, underlying mechanisms responsible for this association remain to be elucidated. Recent findings have elucidated the significance of the accumulation of senescent cells and other inflammatory cells in organs and tissues with age, and their deleterious effects, such as the induction of inflammation in the microenvironment, as underlying factors contributing to organ dysfunction and disease development. Cellular senescence is a cellular phenomenon characterized by a permanent cessation of cell proliferation and secretion of several proinflammatory cytokines (senescence associated secretory phenotypes). Notably, the elimination of senescent cells from aging individuals has been demonstrated to alleviate age-related organ and tissue dysfunction, as well as various geriatric diseases. This review summarizes the molecular mechanisms by which senescent cells are induced and contribute to age-related diseases, as well as the technologies that ameliorate them.

This article is an explanatory review on a study of licorice stored in Shosoin Repository reported in this journal by Dr. Shoji Shibata in 2003 (Proc. Jpn. Acad. Ser. B 79, 176-180). The study using new technologies at that time for identification of plant species was a follow-up research of his own study performed half a century before. The study revised previous results and elucidated that the licorice stored in Shosoin Repository was derived from Glycyeehiza uralensis.

Photoredox catalysis, which facilitates organic transformations under visible-light irradiation, including sunlight, has garnered considerable attention as a cornerstone of green chemistry. Since the early days of this field around 2010, the author's group has made substantial contributions to its advancement. This review article provides a concise overview of the history and fundamental principles of photoredox catalysis, along with highlights of the achievements by the author's group. Although colorless organic compounds cannot be directly activated by visible light, photo-excited colored catalysts, with their two half-occupied frontier orbitals, play dual roles via electron transfer processes with organic substrates. The hole in the lower-energy orbital functions as a single-electron oxidant, whereas the electron in the higher-energy orbital acts as a single-electron reductant, enabling the formation of reactive radical intermediates from diverse organic compounds, including colorless ones. The discussion will focus on the key transformations developed by the author's group, including bimetallic photocatalysis, fluoroalkylation, and catalysis in aqueous media.

The biological activity of hyaluronan (HA), a major component of the extracellular matrix in vertebrate tissues, depends on its molecular weight, and thus its degradation is a critical process for HA biological functions. Here, we review the characteristics of newly discovered proteins essential for HA degradation, hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID), also known as cell migration inducing hyaluronidase 1 (CEMIP) and KIAA1199, and transmembrane protein-2 (TMEM2; alias CEMIP2). Human and mouse forms of HYBID exert their HA-degrading activity in special microenvironments including recycling endosomes. Mouse TMEM2 functions as a cell-surface hyaluronidase for HA turnover in local tissues, lymph nodes, and the liver. In contrast, the role of human TMEM2 in HA degradation is the subject of much debate. HYBID expression is upregulated by proinflammatory factors such as histamine and interleukin-6 and downregulated by transforming growth factor-β. HYBID is involved in physiological HA turnover in human skin and joint tissues and plays an important role in their pathological destruction by accelerating HA degradation.

A characteristic feature of plants is their ability to produce a vast array of metabolites, a trait shaped by their evolution into sessile organisms. Over the past three decades, I have contributed to the development of phytochemical genomics, a field that emerged during the genomic era. Our research group established advanced analytical platforms for plant metabolomics by integrating state-of-the-art instruments with informatics tools. By combining genomics, transcriptomics, and metabolomics, we uncovered novel gene functions and identified new metabolites and gene-metabolite networks. Our study encompassed a broad spectrum of metabolites ranging from primary products, such as amino acids, sulfur-containing compounds, and lipids, to specialized (secondary) compounds, including flavonoids, alkaloids, and terpenoids. Initially, our focus was on the model plant Arabidopsis thaliana; however, we later included crops such as rice and tomato, as well as medicinal plants. This review highlights the key aspects of my research journey.

Sunlight-driven overall water splitting using particulate photocatalysts is of growing interest as a means of producing green hydrogen from water, because systems based on particulate photocatalysts can be spread over large areas using potentially inexpensive processes. Since the first reports on photocatalytic water splitting in 1980, a variety of materials have been developed. Alongside material development, systems designed for the practical implementation of solar hydrogen production technologies using particulate photocatalysts have recently emerged. This review highlights developments in photocatalyst research and examines the current progress in system design for the large-scale production of solar hydrogen (green hydrogen) based on these materials. Such technology represents a crucial solution in the pursuit of a carbon-neutral society-one of the most urgent global challenges.

This review examines the molecular mechanisms controlling the development and homeostasis of the musculoskeletal system through gene expression regulation. It introduces key discoveries from basic transcriptional control to advanced mechanotransduction pathways, focusing on our contributions including the EMBRYS database for transcription factor expression analysis and the identification of RP58 in muscle development and Mohawk (Mkx) in tendon formation. We also elucidated the role of miR-140 as a critical regulator in cartilage development and homeostasis. This microRNA is specifically expressed in cartilage, promotes chondrogenesis, and is involved in protective mechanisms against cartilage degenerative diseases such as osteoarthritis. Our discovery of the PIEZO1-Mkx pathway provides a molecular mechanism linking mechanical stimuli to gene expression in tendons, explaining tissue adaptation and differences in motor abilities. Understanding these pathways offers new therapeutic strategies for tendon and ligament injuries, age-related decline, and cartilage diseases. Currently, we are proposing the concept of "tenopenia" to complement sarcopenia, addressing the mechanisms of age-related tendon deterioration. This integrated approach to the musculoskeletal system as an environment-responsive entity advances both fundamental science and clinical applications aimed at maintaining mobility throughout life.

The term "clone" is commonly used in the medical and life sciences to denote a genetically identical population, at both the individual and cellular levels. The concept of clonal expansion is of fundamental importance in cancer research. The advent of advanced sequencing technologies has elucidated the clonal nature of intermediates between normal cells and cancer cells. This review underscores seminal discoveries in the blood and stratified squamous epithelial systems, emphasizing the pivotal role of mutations in DNA modifier genes and Notch pathway genes, respectively, as drivers of clonal expansion. Despite the distinct nature of these systems and their genetic backgrounds, a common biological principle emerges.

Transcription is an essential biological process that underlies all cellular and organismal activities. In eukaryotes, RNA polymerase II (RNAPII) transcribes every protein-coding gene and many non-coding genes, playing a central role in gene expression. Transcription generally occurs in three steps: RNAPII initiates transcription from a gene promoter, elongates RNA as it traverses the gene body, and terminates transcription at the end of the gene. Dynamic interactions with multiple accessory factors allow RNAPII to form functional transcription complexes and accomplish these processes in chromatin. Recent progress in structural biology has illuminated the structural and mechanistic details of RNAPII functions, particularly promoter-proximal pausing, nucleosome transcription, and transcription termination. This review provides a survey of these advances and discusses future directions.

Natural products that exhibit significant biological activity often possess complex molecular structures such as caged frameworks, strained motifs, inherent instability, and many stereogenic carbon centers, etc. Achievement of those total syntheses always requires the powerful methodologies and judicious strategies to fulfill the stereochemical requirements of the target compounds. Building on our successful stereo-controlled syntheses, we have established the concept of conformational constraint, which renders the approach of reactants under a controlled manner during the bond-forming process through the best orbital overlap. Important factors that affect the proper orientation of substrates are (i) acyclic allyl strain, (ii) stereoelectronic effect, (iii) chelation control, etc. Established methodologies include (i) heteroatom directed conjugate addition for diastereoselective C-C bond formation, (ii) 100% α-selective C-glycosidation by using alkynyl-silane, (iii) cobalt acetylene chemistry for medium-size ring formation, followed by its functional group transformation. The author has named such total concept as conformational constraint and has illustrated it with the finished examples of total syntheses. These examples are taken from maytansine, okadaic acid, tautomycin, tetrodotoxin, ciguatoxin, etc.

Tissue-resident macrophages perform indispensable functions in the development, maintenance, and repair of tissues. Microglia are the primary resident immune cells in the central nervous system (CNS), functioning as intracerebral macrophages distributed throughout the brain parenchyma. In addition to microglia, there is another, less well-characterized type of macrophage known as CNS border-associated macrophages (CAMs), and the existence of these cells has been recognized for several decades. With recent advances in research technologies, an increasing number of studies have focused on CAMs, and our understanding of them has begun to improve. In this article, we review the cellular characteristics and functions of CAMs that have been elucidated thus far, with a particular focus on the similarities and differences between CAMs and microglia.

In 2001, we launched the Hokkaido Study, the first prospective birth cohort study in Japan. We are currently tracking the effects of environmental chemicals, using a life course approach. The study examines life circumstances after birth, and the longest follow-up to date is 20 years of age. We have measured prenatal exposure to dioxins, organochlorine pesticides, per- and polyfluoroalkyl substances, plasticizers such as di(2-ethylhexyl) phthalate, and bisphenol A. Our findings have mostly revealed that increased exposure to these environmental chemicals is linked to increased risk of lower birth size, effects on thyroid and steroid hormones, adipokine levels, as well as disruption of neurodevelopment, including causing asthma and respiratory symptoms. However, it should be noted that our findings also include protective or null findings, which may be due to low chemical concentrations or differences in prenatal or postnatal exposure. We would like to emphasize the importance of long-term continuation of the cohort, effective utilization of the data, and application of the results to environmental and health policies.

Evapotranspiration is a critical factor that plays a pivotal role in irrigation and water resource planning. It is also a major influence with regard to global warming issues. Therefore, several studies have been performed on the estimation methods for evapotranspiration; however, the most prevalent method used over a long period to estimate evapotranspiration is the complementary relationship approach. Recently, this method was modified to improve its symmetry and accuracy. However, to achieve better performance, a different evapotranspiration estimation method using an inverse analysis of the Bowen ratio was proposed by us in an earlier study. In order to present a performance comparison of these different estimation methods, the reproducibility of three types of complementary relationship methods and inverse analysis methods was assessed in this study. Our study utilized data from FLUXNET2015 and evaluated the performance of the methods using regression analysis and root mean square error (RMSE) with data from 15 test sites, mainly located in the U.S.A., for a total period of 132 years. From the results, it was observed that the inverse analysis approach demonstrated a slightly better performance than the complementary relationship methods. This study provides a valuable direction for future research works on the estimation of evapotranspiration.