Tsukuba International University

Elevated phosphate concentration in proximal tubular fluid promotes calcium phosphate microcrystallopathy, thereby accelerating the progression of chronic kidney disease (CKD). However, the clinical significance of proximal tubular phosphate exposure in humans remains uncertain. We aimed to determine whether estimated proximal tubular fluid phosphate concentration (ePTFp) is independently associated with age-related kidney function decline in adults with and without CKD. We conducted a 5-year prospective cohort study involving 308 adults with and without CKD. ePTFp-a novel, noninvasive index-and serum fibroblast growth factor 23 (FGF23) concentrations were derived from blood and urine measurements. Kidney function decline, expressed as estimated glomerular filtration rate (eGFR) slope, was modeled using linear mixed-effects analysis. Associations of ePTFp and serum FGF23 with eGFR slope were examined using multivariable regression analysis, adjusting for potential covariates at baseline, including age, sex, several comorbidities, current smoking status, eGFR, and urinary glomerular and tubular injury markers. Over 5 years, eGFR declined in participants with and without CKD, with a steeper decline in those with CKD. Higher baseline ePTFp and serum FGF23 were inversely correlated with eGFR slope. In multiple adjusted models, elevated ePTFp remained independently associated with faster eGFR decline, whereas the serum FGF23 association was attenuated after covariate adjustment. Elevated ePTFp was independently linked to accelerated kidney function decline, underscoring the clinical relevance of calcium phosphate microcrystallopathy. ePTFp may represent a practical biomarker with implications for prevention and treatment strategies targeting the aging kidney with proximal tubular phosphate exposure.

BackgroundChildren and adolescents with autism spectrum disorder (ASD) frequently experience sleep problems. Although various pharmacological, behavioral, and physical interventions have demonstrated efficacy in improving sleep among children with ASD, the relative effectiveness of these interventions remains unclear.MethodsWe will conduct a systematic literature search to identify randomized controlled trials that evaluate the efficacy of pharmacological (e.g., melatonin), psychological (e.g., cognitive behavioral therapy), and physical (e.g., bright light therapy) interventions for sleep problems in children with ASD. We will search PubMed, PsycINFO, Cochrane CENTRAL, major trial registries, and regulatory agency websites. We will assess the Cochrane Risk of Bias 2.0 (RoB 2.0) tool for primary outcome and the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool for the bias due to missing network evidence. A network meta-analysis (NMA) will be performed to compare the included interventions. The primary outcome will be sleep onset latency, while secondary outcomes will include other sleep variables, all-cause dropouts, and sleep disturbances assessed using standardized measures. We will assess confidence in NMA(CINeMA).DiscussionOur NMA aims to provide evidence-based insights into the effectiveness of sleep interventions for clinicians, children with ASD, and their caregivers. This information will help guide treatment decisions and improve the quality of life for children with ASD and their families.Systematic review registrationPROSPERO CRD42024592795.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13643-026-03143-8.

ABSTRACT This study aimed to identify the optimal transition velocities between streamlined glide (SL), underwater dolphin kick (DK), and front crawl (FC) during high-speed swimming. Ten elite female swimmers performed front crawl and dolphin kick trials in a long-course pool, and repeated the same motions under tethered conditions in a water flume to measure net force. Power-law fitting was applied to model net force as a function of flow velocity across the three movement conditions. The results revealed distinct patterns in the scaling coefficients A and exponents n , following the order: A SL > A DK > A FC and n SL < n DK < n FC . The fitted net force curves intersected at two velocities, U SL − DK and U DK − FC , and for most swimmers, these intersection velocities exceeded their respective constant velocities, V DK _ const and V FC _ const . These intersection points indicate the optimal timing for initiating propulsive actions to minimise deceleration during the post-start and post-turn phases. A conceptual model was proposed to explain the phase transition strategy based on velocity-dependent net force profiles. Although individual variation was observed, most swimmers exhibited similar trends, supporting the applicability of the model. These findings provide a fluid mechanical perspective for optimising underwater strategies and may contribute to enhanced start and turn performance in competitive swimming.

We investigated the role of position-dependent memorability and input dynamics in password recall tasks. Eight participants performed a 2 (length: 6-character vs. 8-character) × 4 (character set: numeric/alphabetic/alphanumeric/alphanumeric + symbols) task with physiological and behavioral measures (EEG, blink index, keystroke logs). Generalized estimating equations (GEE) confirmed a robust sequential position effect: accuracy declined toward later positions in the 6-character sequence, with this trend being even more pronounced in the 8-character sequence. The immediate interkey interval (IKI) negatively predicted character-level accuracy, suggesting that local reaction delay serves as a proximal marker for recall failure. In contrast, simple Spearman correlations between accuracy, self-reported fatigue, EEG band power, blink indicators, and reverse digit span were small and non-significant. These findings reaffirm the universality of sequential position mechanisms in mixed-character stimuli and identify IKI as a practical behavioral metric for interface design. We discuss creating passwords that balance usability and robustness.

ABSTRACTAlterations in the immune system, stemming from sleep/wakefulness disorders, increase the risk of inflammatory pathologies. Orexin, a hypothalamic neuropeptide, regulates sleep and wakefulness. However, the role of orexin in inflammatory responses—whether it is protective or pathological—is still unclear. In this study, our aim was to elucidate the role of orexin in sleep and inflammatory states through the examination of a lipopolysaccharide (LPS)‐induced systemic inflammatory model and the effects of daridorexant, a dual orexin receptor antagonist. Intraperitoneal LPS administration significantly decreased rapid eye‐movement (REM) sleep and wakefulness while increasing non‐REM sleep. Pretreatment with daridorexant enhanced REM sleep recovery in LPS‐induced systemic inflammation, evidenced by extended duration and increased episode frequency. Transcriptomic profiling demonstrated a rise in the expression of pro‐inflammatory cytokines (Cxcl1, Ccl2, Ccl7, and Tnf) within the hypothalamus of LPS‐challenged mice, which was mitigated by daridorexant administration. In addition, daridorexant mitigated LPS‐induced acute lung inflammation. These findings suggest that by reducing pro‐inflammatory cytokine expression, the inhibition of orexin activity mitigates the lethargy associated with systemic inflammation, while also improving sleep quality. This study explores the potential of orexin receptor antagonists as strategic options for inflammatory pathologies and their associated sleep disorders.

The circadian clock drives daily rhythms of gene expression and physiology. Advances in next-generation DNA sequencing have provided extensive insights into RNA expression, but more functional information at the protein level with sufficient depth has been limited by technical challenges. In this study, we generated a comprehensive mouse circadian proteome atlas (https://chronoproteinology.org/circadian_atlas) by analyzing 32 tissues, including the suprachiasmatic nucleus (SCN), using the next-generation mass spectrometer Orbitrap Astral. Data-independent acquisition of 584 samples, including developmental samples, revealed the spatiotemporal profiles of about 19,000 proteins. Proteome and phospho-proteome analyses of whole-cell and nuclear proteins in the liver revealed circadian changes in protein quantity and quality, as well as global changes in hPER2-S662G mutant mice, a genetic model of human familial advanced sleep phase (FASP). This multi-tissue circadian proteome atlas provides a fundamental resource for understanding when, where, and which proteins are expressed and function.

Daytime napping improves performance, which is maximized with a post-N2 9-min nap. We evaluated whether a system that enables optimal-time automatic awakening using blood flow parameters could improve performance, sleepiness, and fatigue compared to no-nap. Additionally, we investigated whether its performance was comparable to manual awakening based on polysomnography. Eighty-one healthy adults (33.6 ± 12.8 years) were randomly assigned to automatic- or manual-awakening or rest groups. A task bout comprising a digit-symbol substitution test (DSST), visual detection test, and sleepiness and fatigue questionnaires was performed three times per session before napping and for six sessions after napping. In all post-nap sessions, sleepiness and fatigue in the automatic awakening group decreased, compared to the rest group, and were comparable to those in the manual awakening group. The DSST improved in the sixth post-nap session for the manual awakening group compared to the rest group; no improvement was observed in the automatic awakening group. The system model was refined by adding training data and tested on 50 healthy adults (40.6 ± 13.1 years). The test results revealed that the N2 detection accuracy of the system improved. The optimal automatic awakening system improves subjective sleepiness and fatigue, and further improvements in its accuracy may enhance post-nap performance.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21008-3.

Fetal development in endothermic mammals relies on a tightly regulated maternal body temperature. In animal models, deviations from normothermia during gestation cause fetal developmental abnormalities. However, the direct and physiological manipulation of the maternal core temperature has been technologically challenging, as traditional methods involve the imposition of external thermal stress. Recent advances in the identification of thermoregulatory neurons in the mouse preoptic area have allowed precise control of maternal body temperature without altering environmental conditions. Here we show that the activation of excitatory neurons in the medial preoptic area (MPO) induces a torpor-like hypothermic state in pregnant mice. When induced during early gestation, this state resulted in pregnancy loss, likely due to implantation failure. Hypothermia in mid- and late-gestation reduced fetal liver and kidney size and caused severe growth retardation. Similar outcomes were observed following pyroglutamylated RFamide peptide (Qrfp)-expressing neuron activation in the MPO, whereas inhibitory neuron activation had minimal effect. Furthermore, activating MPO excitatory neurons projecting to the dorsomedial hypothalamic nucleus reproduced both the torpor-like state and fetal growth retardation. These results underscore the importance of a stable maternal body temperature in fetal development and establish a new model for studying the effects of altered maternal temperature on embryogenesis.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21115-1.

Traumatic brain injury (TBI) triggers a cascade of secondary pathologies—such as neuroinflammation and glial activation—contributing to progressive neuronal loss and hindering functional recovery. While therapeutic hypothermia has shown neuroprotective potential, its clinical application is limited by systemic complications. Recent discoveries have identified hypothalamic Q neurons, whose activation induces a reversible, hibernation-like hypothermic state, termed Q neuron-induced hypothermic/hypometabolic states (QIH), without the need for external cooling. However, whether QIH can mitigate brain injury remains unknown. In this study, we examined the therapeutic effects of QIH following acute brain injury in male mice. Using a dorsal striatal stab injury model, we found that QIH-treated mice displayed significantly improved motor performance and grip strength compared with controls. Histological analyses revealed enhanced neuronal survival in the perilesional striatum, accompanied by markedly reduced astrocytic gliosis and microglial accumulation at the injury site. To investigate the mechanisms underlying these improvements, we employed a medial prefrontal cortex injury model and observed that QIH robustly suppressed astrocytic and microglial activation, as indicated by reduced GFAP and Iba1 expression. Additionally, QIH decreased the number of CD16/32- and CD68-positive microglia and downregulated iNOS expression, suggesting that QIH dampens both oxidative and phagocytic inflammatory responses. Morphometric analysis further revealed a shift toward ramified and rod-shaped microglia, phenotypes associated with neuroprotection. Our findings demonstrate that QIH ameliorates early neuroinflammation, preserves neuronal integrity, and promotes functional recovery following brain injury. These results highlight QIH as a novel and physiologically grounded neuroprotective strategy that may overcome the limitations of conventional hypothermia-based interventions.