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Olivia Sjöland,1,2 Thomas Svensson,1– 3 Kaushalya Madhawa,1 Hoang NT,1 Ung-Il Chung,1,3,4 Akiko Kishi Svensson1,2,5 1Precision Health, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan; 2Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; 3Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki-Ku, Kawasaki-Shi, Kanagawa, Japan; 4Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, Tokyo, Japan; 5Department of Diabetes and Metabolic Diseases, The University of Tokyo, Tokyo, JapanCorrespondence: Thomas Svensson, Precision Health, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan, Tel +81-3-5841-4737, Email thomas.svensson@med.lu.seBackground: Associations between subjective sleep quality and stage-specific heart rate (HR) may have important clinical relevance when aiming to optimize sleep and overall health. The majority of previously studies have been performed during short periods under laboratory-based conditions. The aim of this study was to investigate the associations of subjective sleep quality with heart rate during REM sleep (HR REMS) and non-REM sleep (HR NREMS) using a wearable device (Fitbit Versa).Methods: This is a secondary analysis of data from the intervention group of a randomized controlled trial (RCT) performed between December 3, 2018, and March 2, 2019, in Tokyo, Japan. The intervention group consisted of 179 Japanese office workers with metabolic syndrome (MetS), Pre-MetS or a high risk of developing MetS. HR was collected with a wearable device and sleep quality was assessed with a mobile application where participants answered The St. Mary’s Hospital Sleep Questionnaire. Both HR and sleep quality was collected daily for a period of 90 days. Associations of between-individual and within-individual sleep quality with HR REMS and HR NREMS were analyzed with multi-level model regression in 3 multivariate models.Results: The cohort consisted of 92.6% men (n=151) with a mean age (± standard deviation) of 44.1 (± 7.5) years. A non-significant inverse between-individual association was observed for sleep quality with HR REMS (HR REMS − 0.18; 95% CI − 0.61, 0.24) and HR NREMS (HR NREMS − 0.23; 95% CI − 0.66, 0.21), in the final multivariable adjusted models; a statistically significant inverse within-individual association was observed for sleep quality with HR REMS (HR REMS − 0.21 95% CI − 0.27, − 0.15) and HR NREMS (HR NREMS − 0.21 95% CI − 0.27, − 0.14) after final adjustments for covariates.Conclusion: The present study shows a statistically significant within-individual association of subjective sleep quality with HR REMS and HR NREMS. These findings emphasize the importance of considering sleep quality on the individual level. The results may contribute to early detection and prevention of diseases associated with sleep quality which may have important implications on public health given the high prevalence of sleep disturbances in the population.Keywords: sleep quality, heart rate, sleep stages, REMS, NREMS, wearable device

Stretchable electronic devices should be enabled by the smart design of materials and architectures because their commercialization is limited by the tradeoff between stretchability and electrical performance limits. In this study, thin‐film transistors are fabricated using strategies that combine the unit process of a novel hybrid gate insulator and low‐temperature indium gallium tin oxide (IGTO) channel layer and a stress‐relief substrate structure. Novel hybrid dielectric films are synthesized and their molecular structural configurations are analyzed. These films consist of a polymer [poly(4‐vinylphenol‐co‐methylmethacrylate)], cross‐linkers having different binding structures [1,6‐bis(trimethoxysilyl)hexane (BTMSH), dodecyltrimethoxysilane, and poly(melamine‐co‐formaldehyde)], and an inorganic zirconia component (ZrOx). The hybrid film with BTMSH cross‐linker and 0.2 M ZrOx exhibits excellent insulating properties as well as mechanical stretchability. IGTO transistors fabricated on polyimide‐coated glass substrates are transferred to the rubber substrate to offer stretchability of the transistor pixelated thin‐film transistors. IGTO transistors fabricated on stretchable substrates using these strategies show promising electrical performance and mechanical durability. After 200 stretchability test cycles under uniaxial elongation of approximately 300%, the IGTO transistor still retains a high carrier mobility of 21.7 cm2 V−1 s−1, a low sub‐threshold gate swing of 0.68 V decade−1 and a high ION/OFF ratio of 2.0 × 107. [ABSTRACT FROM AUTHOR]

Amorphous sputter-deposited NiTi thin films were subjected to pulsed, melt-mediated laser crystallization techniques to engineer their microstructure. The effects of laser processing of preheated films are examined. Laser processing of films at an elevated substrate temperature has a significant effect on the rate with which solidification occurs. It is observed that the preheating temperature at which processing is carried out has significant implications for the resulting phase and microstructure, and therefore mechanical properties. Furthermore, the microstructural effects of varying incident laser energy density are examined via atomic force microscopy, scanning electron microscopy, and x-ray diffraction, and mechanical/shape memory properties are characterized via nanoindentation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To establish a cell culture system for noninvasive and real-time monitoring of chondrogenic differentiation in order to screen for chondrogenic factors. METHODS: The optimum reporter construct transfected into chondrogenic ATDC5 cells was selected by a luciferase reporter assay and fluorescence analysis during cultures with insulin. The established cell line was validated according to its fluorescence following stimulation with SOX proteins, bone morphogenetic protein 2 (BMP-2), or transforming growth factor beta (TGFbeta) and was compared with the level of messenger RNA for COL2A1 as well as with the degree of Alcian blue staining. Screening of chondrogenic factors was performed by expression cloning using a retroviral expression library prepared from human tracheal cartilage. The expression pattern of the identified molecule was examined by in situ hybridization and immunohistochemistry. Functional analysis was performed by transfection of the identified gene, the small interfering RNA, and the mutated gene. RESULTS: We established an ATDC5 cell line with 4 repeats of a highly conserved enhancer ligated to a COL2A1 basal promoter and the DsRed2 reporter (ATDC5-C2ER). Fluorescence was induced under the stimulations with SOX proteins, BMP-2, or TGFbeta, showing good correspondence to the chondrogenic markers. Screening using the ATDC5-C2ER system identified several chondrogenic factors, including sorting nexin 19 (SNX19). SNX19 was expressed in the limb cartilage of mouse embryos and in the degraded cartilage of adult mouse knee joints during osteoarthritis progression. The gain-of-function and loss-of-function analyses revealed a potent chondrogenic activity of SNX19. CONCLUSION: We established the ATDC5-C2ER system for efficient monitoring of chondrogenic differentiation by fluorescence analysis, and we identified a novel chondrogenic factor (SNX19) using this system. This system will be useful for elucidating the molecular network of chondrogenic differentiation. [ABSTRACT FROM AUTHOR]

This study examined the effect of spark plasma sintering (SPS) on the densification behavior and resulting dielectric and piezoelectric properties of Pb(Mg1/3Nb2/3)O3–35 mol% PbTiO3 ceramics with a 5 mol% excess of PbO. Through normal sintering at 1200∘C, the density of the specimen reached only 92% of the theoretical density (TD). However, with the SPS treatment, the density of the PMN-PT ceramics increased to more than 99% of the TD at 900∘C, and maintained over 98% of the TD during subsequent heat-treatment at 1200∘C for 10 h. The increased density of the Pb(Mg1/3Nb2/3)O3–35 mol% PbTiO3 ceramics resulted in an improvement in the dielectric and piezoelectric properties. The SPS treatment was also successfully applied to the densification of a PMN-PT single crystal grown on a BaTiO3 seed crystal using a solid-state crystal growth (SSCG) process. [ABSTRACT FROM AUTHOR]

The shape of (Ba0.35Sr0.65)TiO3 (BST) grains and their coarsening behavior were investigated as a function of temperature. The BST grains exhibit a morphological change at approximately 1410 °C; the grains were angular at 1390 °C and corner-rounded at 1420 °C. At 1390 °C, a few very large grains appear in the microstructure. Such abnormal grain growth is explained in terms of a coarsening advantage due to the Σ3 coincident site lattice (CSL) boundaries. On the other hand, at 1420 °C, normal grain growth was observed to occur. The change in coarsening behavior with temperature is related to the structural transition of the interface. [Copyright &y& Elsevier]

Purpose of Review: This review paper provides step-by-step instructions on the fundamental process, from handling fastq datasets to illustrating plots and drawing trajectories., Recent Findings: The number of studies using single-cell RNA-seq (scRNA-seq) is increasing. scRNA-seq revealed the heterogeneity or diversity of the cellular populations. scRNA-seq also provides insight into the interactions between different cell types. User-friendly scRNA-seq packages for ligand-receptor interactions and trajectory analyses are available. In skeletal biology, osteoclast differentiation, fracture healing, ectopic ossification, human bone development, and the bone marrow niche have been examined using scRNA-seq. scRNA-seq data analysis tools are still being developed, even at the fundamental step of dataset integration. However, updating the latest information is difficult for many researchers. Investigators and reviewers must share their knowledge of in silico scRNA-seq for better biological interpretation. This review article aims to provide a useful guide for complex analytical processes in single-cell RNA-seq data analysis., (© 2024. The Author(s).)

This study aims to elucidate the origin of nonlinear stress relaxation behaviors in transient networks using a systematically controlled model system consisting of the tetra-armed polyethylene glycols (Tetra-PEG slime) in conjunction with two-dimensional rheo-optics observations. Transient networks, characterized by their temporary cross-links, are extensively utilized in self-healing and robust materials. However, the molecular mechanisms governing their viscoelastic responses to large deformations have remained elusive. This is primarily due to the heterogeneous structures inherent in conventional transient networks and a scarcity of detailed experimental evaluations. By employing Tetra-PEG slime, which is distinguished by its regular structure with uniform strand lengths and functionalities, and the polarization imaging method, we overcome these obstacles. Our results reveal that the damping phenomena observed under large step strains arise from spatially heterogeneous relaxation, predominantly driven by network strand pullout. These insights lay a solid foundation for understanding the intricate rheological properties of transient networks.

Objectives: This study aimed to investigate the regulatory mechanisms governing dental mesenchymal cell commitment during tooth development, focusing on odontoblast differentiation and the role of epigenetic regulation in this process., Methods: We performed single-cell RNA sequencing (scRNA-seq) of dental cells from embryonic day 14.5 (E14.5) mice to understand the heterogeneity of developing tooth germ cells. Computational analyses including gene regulatory network (GRN) assessment were conducted. We validated our findings using immunohistochemistry (IHC) and in vitro loss-of-function analyses using the DNA methyltransferase 1 (DNMT1) inhibitor Gsk-3484862 in primary dental mesenchymal cells (DMCs) isolated from E14.5 mouse tooth germs. Bulk RNA-seq of Gsk-3484862-treated DMCs was performed to identify potential downstream targets of DNMT1., Results: scRNA-seq analysis revealed diverse cell populations within the tooth germs, including epithelial, mesenchymal, immune, and muscle cells. Using single-cell regulatory network inference and clustering (SCENIC), we identified Dnmt1 as a key regulator of early odontoblast development. IHC analysis showed the ubiquitous expression of DNMT1 in the dental papilla and epithelium. Bulk RNA-seq of cultured DMCs showed that Gsk-3484862 treatment upregulated odontoblast-related genes, whereas genes associated with cell division and the cell cycle were downregulated. Integrated analysis of bulk RNA-seq data with scRNA-seq SCENIC profiles was used to identify the potential Dnmt1 target genes., Conclusions: Dnmt1 may negatively affect odontoblast commitment and differentiation during tooth development. These findings contribute to a better understanding of the molecular mechanisms underlying tooth development and future development of hard-tissue regenerative therapies., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are natural carriers for intercellular communication within the human body. Mimicking and utilizing EVs by combining them with artificial nanocarriers such as liposomes for drug delivery has garnered considerable attention. However, current technologies for manipulating EVs to facilitate their fusion with liposomes are limited; the existing technique of polyethylene glycol (PEG)-induced fusion is highly inefficient for fusion. In our previous study, we demonstrated that membrane fusion could be induced by Tat peptide (YGRKKRRQRRR)-conjugated poly(ethylene glycol)-phospholipids (Tat-PEG-lipids), in which the Tat peptide and lipid domain facilitate membrane attachment and subsequent fusion between cells and liposomes. This approach is promising for forming EV and liposomal hybrids. In this study, we aim to fuse EVs and liposomes using Tat-PEG-lipids. We isolated and characterized EVs derived from HEK293T cell culture medium and treated a mixture of EVs and liposomes composed of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine and cholesterol (1:1, molar ratio), with Tat-PEG-lipids with different lipid chain lengths. Here, we used nonanoyl (C9), dodecanoyl (C12), and myristoyl (C14) groups as lipid anchors with 5 kDa PEG chains. Dynamic light scattering analysis revealed a large increase in the apparent size of mixture of EVs and liposomes by adding Tat-PEG-lipids (especially C14, C12, followed by C9). Fluorescence resonance energy transfer, confocal laser scanning microscopy, and transmission electron microscopy, used to analyze the reaction process, revealed that the membrane fusion occurred between EVs and liposomes but not their aggregates. The short lipid domain of Tat-PEG-lipids effectively induced membrane fusion and the formation of hybrid EVs and liposomes. Thus, Tat-PEG-lipids (C9 and C12) could be promising candidates for inducing membrane fusion to fabricate EV-liposome hybrids., Competing Interests: The authors (Yuya Sato, Weixu Zhang, Teruhiko Baba, Ung-il Chung, and Yuji Teramura) declare no conflict of interest for this manuscript., (© 2024 The Author(s).)

Purpose: To evaluate the validity and the reliability of the Oura Ring Generation 3 (Gen3) with Oura Sleep Staging Algorithm 2.0 (OSSA 2.0) through multi-night polysomnography (PSG)., Participants and Methods: Participants were 96 generally healthy Japanese men and women aged between 20 and 70 years contributing with 421,045 30-s epochs. Sleep scoring was performed according to American Academy of Sleep Medicine criteria. Each participant could contribute with a maximum of three polysomnography (PSG) nights. Within-participant means were created for each sleep measure and paired t-tests were used to compare equivalent measures obtained from the PSG and Oura Rings (non-dominant and dominant hand). Agreement between sleep measures were assessed using Bland-Altman plots. Interrater reliability for epoch accuracy was determined by prevalence-adjusted and bias-adjusted kappa (PABAK)., Results: The Oura Ring did not significantly differ from PSG for the measures time in bed, total sleep time, sleep onset latency, sleep period time, wake after sleep onset, time spent in light sleep, and time spent in deep sleep. Oura Rings worn on the non-dominant- and dominant-hand underestimated sleep efficiency by 1.1 %-1.5 % and time spent in REM sleep by 4.1-5.6 min. The Oura Ring had a sensitivity of 94.4 %-94.5 %, specificity of 73.0 %-74.6 %, a predictive value for sleep of 95.9 %-96.1 %, a predictive value for wake of 66.6 %-67.0 %, and accuracy of 91.7 %-91.8 %. PABAK was 0.83-0.84 and reliability was 94.8 %. Sleep staging accuracy ranged between 75.5 % (light sleep) and 90.6 % (REM sleep)., Conclusions: The Oura Ring Gen3 with OSSA 2.0 shows good agreement with PSG for global sleep measures and time spent in light and deep sleep., Competing Interests: Declaration of competing interest Thomas Svensson reports financial support was provided by Oura Health Oy. Ung-il Chung reports financial support was provided by Oura Health Oy. Akiko Kishi Svensson reports financial support was provided by Oura Health Oy. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Dementia is highly prevalent in Japan, a super-aged society where almost a third of the population is above 65 years old. Japan has been implementing ageing and dementia policies since 2000 and now has a wealth of experience to share with other nations who are anticipating a similar future regarding dementia. This article focuses on the 2019 National Framework for Promotion of Dementia Policies that, based on its philosophy of Inclusion and Risk Reduction, lays out five complementary strategies. Together, these five strategies encourage a whole of society approach in dementia care. We first elaborate on the activities being undertaken under each of these strategies and then discuss the future challenges that Japan needs to address. These policy and social innovations spearheaded by Japan can be useful information for other countries that are anticipating similar future as Japan., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Hydrogels, which have polymer networks through supramolecular and reversible interactions, exhibit various mechanical responsibilities to its surroundings. The influence of the reversible bonds on a hydrogel's macroscopic properties, such as viscoelasticity and dynamics, is not fully understood, preventing further innovative material development. To understand the relationships between the mechanical properties and molecular structures, it is required to clarify the molecular understanding of the networks solely crosslinked by reversible interactions, termed "transient networks". This review introduces our recent progress on the studies on the molecular mechanism of viscoelasticity in transient networks using multiple methods and model materials. Based on the combination of the viscoelasticity and diffusion measurements, the viscoelastic relaxation of transient networks does not undergo the diffusion of polymers, which is not explained by the framework of conventional molecular models for the viscoelasticity of polymers. Then, we show the results of the comparison between the viscoelastic relaxation and binding dynamics of reversible bonds. Viscoelastic relaxation is primarily affected by "dissociation dynamics of the bonds" and "network structures". These results are explained in the framework that the backbone, which is composed of essential chains supporting the stress, is broken by multiple dissociation events. This understanding of molecular dynamics in viscoelasticity will provide the foundation for designing transient networks.

Cosmic large-scale structures, animal flocks and living tissues can be considered non-equilibrium organized systems created by dissipative processes. Replicating such properties in artificial systems is still difficult. Herein we report a dissipative network formation process in a dilute polymer-water mixture that leads to percolation-induced gel-gel phase separation. The dilute system, which forms a monophase structure at the percolation threshold, spontaneously separates into two co-continuous gel phases with a submillimetre scale (a dilute-percolated gel) during the deswelling process after the completion of the gelation reaction. The dilute-percolated gel, which contains 99% water, exhibits unexpected hydrophobicity and induces the development of adipose-like tissues in subcutaneous tissues. These findings support the development of dissipative structures with advanced functionalities for distinct applications, ranging from physical chemistry to tissue engineering., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

With the rising prevalence of bone-related injuries, it is crucial to improve treatments for fractures and defects. Tissue engineering offers a promising solution in the form of injectable hydrogel scaffolds that can sustain the release of growth factors like bone morphogenetic protein-2 (BMP-2) for bone repair. Recently, we discovered that tetra-PEG hydrogels (Tetra gels) undergo gel-gel phase separation (GGPS) at low polymer content, resulting in hydrophobicity and tissue affinity. In this work, we examined the potential of a newer class of gel, the oligo-tetra-PEG gel (Oligo gel), as a growth factor-releasing scaffold. We investigated the extent of GGPS occurring in the two gels and assessed their ability to sustain BMP-2 release and osteogenic potential in a mouse calvarial defect model. The Oligo gel underwent a greater degree of GGPS than the Tetra gel, exhibiting higher turbidity, hydrophobicity, and pore formation. The Oligo gel demonstrated sustained protein or growth factor release over a 21-day period from protein release kinetics and osteogenic cell differentiation studies. Finally, BMP-2-loaded Oligo gels achieved complete regeneration of critical-sized calvarial defects within 28 days, significantly outperforming Tetra gels. The easy formulation, injectability, and capacity for sustained release makes the Oligo gel a promising candidate therapeutic biomaterial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)