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Abstract Kidney organoids are connected to the host circulation and mature after transplantation. However, they are still immature compared to the adult kidneys, and their precise maturation stages remain unclear. By transplanting the mouse embryonic kidney as a model system for organoid transplantation, we report here the maturation defects of the graft, especially in the medulla. Single cell profiling of the developing kidneys in vivo identified gene sets associated with the maturation of the collecting duct epithelium and medullary stroma. These data revealed an upregulation of genes associated with channel/transporter functions and immune defense, as well as a downregulation of neuronal genes. Using these marker genes, we found that the maturation of the collecting duct and medullary stroma in the grafts barely corresponds to the perinatal stage, which was confirmed histologically by using representative genes. Thus, the gene sets obtained serve as maturation coordinates for the renal medulla and will be helpful in analyzing its maturation defects after transplantation. They will also provide a useful basis for further maturation of transplanted kidney organoids.

Abstract There is an urgent need for novel methods that can accurately predict intestinal absorption of orally administered drugs in humans. This study aimed to evaluate the potential of a novel gut microphysiological system (MPS), gut MPS/Fluid3D-X, to assess the intestinal absorption of drugs in humans. The gut MPS/Fluid3D-X model was constructed using a newly developed flow-controllable and dimethylpolysiloxane-free MPS device (Fluid3D-X®). Human induced pluripotent stem cells-derived small intestinal epithelial cells were employed in this model, which exhibited key characteristics of the human absorptive epithelial cells of the small intestine, including the expression of key gene transcripts responsible for drug transport and metabolism, and the presence of dome-like protrusions in the primary intestinal epithelium under air-liquid interface culture conditions. Functional studies of transporters in the constructed model demonstrated basal-to-apical directional transport of sulfasalazine and quinidine, substrates of the active efflux transporters breast cancer resistance protein and P-glycoprotein, respectively, which were diminished by inhibitors. Furthermore, a cytochrome P450 (CYP) 3A inhibitor increased the apical-to-basal transport of midazolam, a typical CYP3A4 substrate, and reduced metabolite formation. These results suggest that gut MPS/Fluid3D-X has the potential to assess the intestinal absorption of small-molecule drugs.

Abstract This study employs Conversation Analysis to create a recursive model that improves the quality of human-robot interaction. Our research goal is to create a dialogue robot that offers pleasant experiences for users, so they are willing to engage in repeated interactions in daily lives. While there has been dramatic progress in the performance of dialogue robots, there has been less attention to the importance of users’ interactional experience compared to the “specs” of the dialogue system. Employing Goffmanian insights and using research in Conversation Analysis (CA), the present study develops a dialogue closing system to exit the interaction. We then experimentally verified that the robot with the dialogue closing system performs better in the user’s perception of the robot (i.e. likeability, politeness, and dialogue satisfaction) than the control group. Further, by analyzing the dialogue between the human and the robot through CA, we propose to build a recursive, reflective model to improve the dialogue model design. A constructive approach urges us to reproduce complicated social phenomena in human-robot interaction so that we can investigate the underlying cognitive mechanisms of humans and create robots that can convey human-like cognition functions and coexist with humans. Taking such a constructive approach, we posit that our recursive model for dialogue systems that uses CA insights and then qualitatively analyzes conversational data can enhance the quality of dialogue systems because the model elucidates which properties of a conversation humans need to experience a conversational robot as human-like. Our study suggests that interactional morality - particularly conversational closings - is one property of human interactions that humans likely require social robots to adhere to.

Abstract Sea ice is regarded as a temporal sink and carrier of microplastics (MPs). Nevertheless, knowledge and understanding of MPs in sea ice remain sparse. This study investigated the abundance, composition, size (> 30 μm), and shape of MPs in four sea-ice cores retrieved at the southern end of the Sea of Okhotsk. Nine microplastic (MP) types, mostly with fragmentary shapes, were detected among ice-core sections. Most fragmentary MPs were smaller than 120 μm, but all fiber MPs were in the largest size class (> 210 μm). MP concentrations were 0–60 particles/L, with an average of 21 particles/L. Higher occurrences of MPs observed in the lower ice layers are attributable to heavier MP contamination in the southern part of the sea and/or relocation of MPs in the ice matrix. No significant correlation was found between the distributions of MP and inorganic particle (sediment) abundances, implying difference in their kinetics of suspension freezing. Taken together, these findings suggest important implications for elucidating the nature and distribution of MPs in sea ice.

Abstract We explored effective therapeutic targets for systemic sclerosis (SSc) patients with high risk for pulmonary arterial hypertension (PAH) by plasma proteomics analysis. A total of fifty-seven patients with SSc were enrolled in the study and the prevalence of PAH was 19.3%. On the other hand, 75.4% of SSc patients showed the ratio of forced vital capacity percentage/diffusing capacity of the lungs for carbon monoxide percentage> 1.6 and met criteria for high risk of PAH. Identification of elevated plasma proteins in SSc patients with high risk of PAH, followed by upstream regulator analysis, predicted interleukin (IL)-17A as a major upstream molecule. Furthermore, we performed in vitro neutralization study using MT-6194, a bispecific antibody targeting both IL-17A and IL-6 receptor. We found that MT-6194 broadly suppressed the increased expression of downstream molecules of IL-17A including IL-17A-related cytokines/chemokines, IL-17A-driven NF $$\kappa$$ B pathway and IL-6-driven JAK/STAT pathway which were shown to be increased in SSc patients with high risk of PAH by the proteomics. Consequently, it is revealed that IL-17A is a promising target for early intervention in SSc patients with high risk for PAH.

Abstract Human gut microbiota plays a crucial role in health and disease. Infancy is a critical period for gut microbiota maturation and immune system development and has the potential to affect long-term health. Understanding the development of gut microbiota in Japanese children is essential because of regional differences and the long-term health effects of the early gut microbiota. However, while several longitudinal studies in Japan have explored the development of the gut microbiota after birth, more extended follow-up periods are still needed. In this study, we aimed to analyze the gut microbiota of 106 Japanese mother–child pairs from the Chiba Study of Mother and Child Health, Japan, over 3.5 years. The results showed that the alpha diversity of the gut microbiota in children increased with age, and its composition began to resemble that of adults. We identified four distinct clusters of gut microbiota that reflected different maturation stages. The similarity between the maternal and child gut microbiota appeared to follow a bimodal-like distribution, suggesting that the presence of older siblings may enhance this similarity. This study highlights the dynamic nature of gut microbiota development in Japanese children and deepens our understanding of the similarities between maternal and child gut microbiota.

Abstract In present investigation, the effort is done to enhance the grain quality in brewer’s rice cultivar Yamadanishiki with the plasma treatment of caryopsis (rice fruit) on ripening process. Seedlings transplanted from a paddy field into pots were grown in a greenhouse, and each caryopsis was treated with plasma on 1, 5, 10 and 15 days after flowering (DAF). The ratio of white-core grains to total number of grains was decreased in the grains treated on DAF1, same level on DAF5, and increased on DAF10 and 15, respectively, compared with control grains. Moreover, same treatment test was conducted with seedlings transplanted from a paddy field into pots and grown in growth chambers equipped with a sensing system to monitor environmental and growth conditions, referred to the climatic conditions of paddy fields. The ratio of white-core grains to total number of grains was decreased in the grains treated on DAF1, and increased on DAF5, 10 and 15, respectively. We demonstrated that plasma treatment of caryopsis affected the formation of white core, and that environmental conditions in the growth chamber were simulated to a paddy field. We would advocate the next-generation agriculture using ICT and plasma, “Smart Agriculture System”, for producing high-quality crops.

Abstract The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing bacteriolytic activities against 81.3% (n = 26) and 78.1% (n = 25) of 32 XDR carbapenemase-producing colistin-resistant K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 and K2/wzi-2. Both phages showed short replication times, large burst sizes with rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both phages are genetically distinct phages from Myoviridae and Podoviridae family, with the lack of toxin, virulence, lysogeny and antibiotic resistance genes. These characteristics highlighted their promising potential for utilizing in phage therapy for combating XDR K. pneumoniae. Although phage cocktail combining vB_kpnM_05 and vB_kpnP_08 provided significant bacteriolysis for longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development of phage resistance under phages’ selection pressures. Future study will be undertaken to elucidate the precise mechanisms by which these XDR K. pneumoniae developed phage resistance and their associated fitness cost. Remarkably, combining phage cocktail with amikacin at their sub-inhibitory concentrations produced potent synergy by completely suppressing bacterial regrowth in vitro. Our study demonstrated the significant therapeutic and prophylactic effectiveness of a phage cocktail-amikacin combination as a promising alternative strategy for overcoming bacteremia associated with XDR K. pneumoniae having carbapenemase and colistin resistance in vivo.

Abstract Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.

Abstract Symbiotic nitrogen fixation is a highly coordinated process involving legume plants and nitrogen-fixing bacteria known as rhizobia. In this study, we investigated a novel Fix− mutant of the model legume Lotus japonicus that develops root nodules with endosymbiotic rhizobia but fails in nitrogen fixation. Map-based cloning identified the causal gene encoding the filamentation temperature-sensitive H (FtsH) protein, designated as LjFtsH4. The LjFtsH4 gene was expressed in all plant organs without increased levels during nodulation. Subcellular localization revealed that LjFtsH4, fused with a fluorescent protein, localized in mitochondria. The Ljftsh4 mutant nodules showed signs of premature senescence, including symbiosome membrane collapse and bacteroid disintegration. Additionally, nodule cells of Ljftsh4 mutant displayed mitochondria with indistinct crista structures. Grafting and complementation tests confirmed that the Fix− phenotype was determined by the root genotype, and that protease activity of LjFtsH4 was essential for nodule nitrogen fixation. Furthermore, the ATP content in Ljftsh4 mutant roots and nodules was lower than in the wild-type, suggesting reduced mitochondrial function. These findings underscore the critical role of LjFtsH4 in effective symbiotic nitrogen fixation in root nodules.

Abstract The tumor microenvironment plays a pivotal role in cancer development. We recently reported that in oral squamous cell carcinoma (OSCC), adipocyte enhancer-binding protein 1 (AEBP1) is abundantly expressed in cancer-associated fibroblasts (CAFs), leading to CAF activation and inhibition of CD8 + T cell infiltration. In the present study, we investigated whether AEBP1 contributes to the destruction and atrophy of muscle tissues in OSCC. By analyzing human skeletal muscle myoblasts (HSMMs), we found that AEBP1 is downregulated during muscle cell differentiation. Transcriptome analysis revealed that AEBP1 knockdown significantly upregulates myogenesis-related genes in HSMMs, and qRT-PCR and western blot analyses confirmed the induction of muscle-related genes, including MYOG, in HSMMs after AEBP1 knockdown. Conversely, ectopic expression of AEBP1 strongly suppressed myogenesis-related genes in HSMMs. Notably, indirect co-culture of HSMMs with OSCC cells led to AEBP1 upregulation and robust suppression of muscle-related genes in HSMMs. Treatment with TGF-β1 also upregulated AEBP1 and suppressed expression of muscle-related genes in HSMMs. Our findings suggest that AEBP1 is a negative regulator of skeletal muscle cell differentiation and that OSCC cells inhibit muscle cell differentiation, at least in part, by inducing AEBP1.

Abstract The Ogasawara Islands, one of the UNESCO World Natural Heritage Site located about 1000 km south of Japan’s main island, harbor numerous endemic species, many of which are as endangered. One of the endemic plant species, Lobelia boninensis, found in the Mukojima, Chichijima, and Hahajima archipelagoes, is endangered due to predation. As part of conservation efforts, translocation is now underway, especially on Chichijima. However, we lack essential information, such as the genetic population structure, to develop appropriate translocation strategies for both wild and planted individuals. Here, we aimed to identify the conservation units and the origin of planted individuals by estimating the genetic population structure and phylogenetic relationships across all habitats of this species. We identified two distinct genetic clusters, indicating genetic differentiation between the northern and southern populations. The genetic population components detected at an isolated site on Chichijima showed a mixture of these distinct clusters, probably due to hybridization. The transplanted individuals in Chichijima were found to have originated from a population in Hahajima. These results suggest the presence of two distinct conservation units. Furthermore, the current translocation strategy poses a risk of genetic contamination between these units, highlighting the need for revised conservation management practices.

Abstract Energy dispersion of electrons is the most fundamental property of the solid state physics. In models of electrons on a lattice with strong geometric frustration, the band dispersion of electrons can disappear due to the quantum destructive interference of the wavefunction. This is called a flat band, and it is known to be the stage for the emergence of various fascinating physical properties. It is a challenging task to realize this flat band in a real material. In this study, we performed first-principles calculations on two compounds, Pb $$_2$$ 2 As $$_2$$ 2 O $$_7$$ 7 and Pb $$_2$$ 2 Sn $$_2$$ 2 O $$_7$$ 7 , which are candidates to have flat bands near the Fermi level. Both compounds have electronic states close to flat bands, but the band width is significantly larger than that of Pb $$_2$$ 2 Sb $$_2$$ 2 O $$_7$$ 7 shown in previous research. Nevertheless, the density of states at the Fermi level of Pb $$_2$$ 2 As $$_2$$ 2 O $$_7$$ 7 is large enough to cause the system to undergo a ferromagnetic transition. In the case of Pb $$_2$$ 2 Sn $$_2$$ 2 O $$_7$$ 7 , pseudo-gap behavior near the Fermi level was observed. These findings underscore the importance of investigating the influence of flat bands on electronic energy dispersion, providing a crucial step toward understanding the emergence and characteristics of flat bands in novel materials.

Abstract Functional maturation of the visual cortex is induced by visual experiences during critical periods. Blind animals and humans exhibit improved auditory abilities after losing their vision. Here we investigated the response of the visual cortex to white noise stimuli during the progression of photoreceptor degeneration in a rat model of blindness (Royal College of Surgeons [RCS] (rdy/rdy) rats). Optical coherence tomography of RCS (+/+) rats with normal visual function revealed normal photoreceptor cells, whereas 3-month-old RCS (rdy/rdy) rats demonstrated photoreceptor cell degeneration. Visual cortex responses (VCRs) to a single flash stimulus were negligible in 3-month-old photoreceptor-degenerated rats. However, VCRs with white noise stimuli were significantly increased in blind versus RCS rats (+/+). Slight changes in the intrinsic optical signals of the control rats were observed on the ventral side of the visual cortex. In contrast, responses were markedly increased throughout the visual cortex of RCS (rdy/rdy) rats. These results indicate that the visual cortex rapidly acquires auditory system function over the first 3 months of life and that the entire visual cortex, rather than just the portion close to the auditory cortex, responds to white noise.

Abstract Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.

Abstract There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6–10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

Abstract Major earthquakes have occurred frequently in Japan throughout history, and the 2024 Noto earthquake is no exception. However, such natural disasters differ in some respects, and specific problems related to these events have also become clear. Kanazawa Medical University Hospital, which was the closest university hospital to the disaster area of the 2024 Noto earthquake, played a crucial role in serving the local community in the wake of the earthquake. The first method used to identify disaster-related patients is to tag them when they are examined by a physician. After confirming that a patient was eligible at the disaster-related patient-determination meeting, patients’ medical information was extracted from the tag name. A total of 421 disaster-related patients were transported and hospitalized by day 31. Fifty-two (14.4%) and 48 (13.3%) patients were admitted for orthopedic surgery and respiratory medicine, respectively. Forty (11.1%) and 38 (10.5%) patients were admitted to cardiology and nephrology departments, respectively. These four departments account for 49.3% of the total. The number of hospitalized patients in the nephrology and orthopedic surgery departments was high immediately after the 2024 Noto Earthquake. We also describe new hospital-specific initiatives and recommendations to improve Kanazawa Medical University Hospital’s system while sharing another hospital experience.

Abstract Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air–blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients.

Abstract Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein (“spike”) as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms.

Abstract GDF15 and FGF21, stress-responsive cytokines primarily secreted from the liver, are promising therapeutic targets for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the interaction between GDF15 and FGF21 remains unclear. We examined the effects of hepatocyte-specific GDF15 or FGF21 overexpression in high-fat diet (HFD)-fed mice for 8 weeks. Hydrodynamic injection of GDF15 or FGF21 sustained high circulating levels of GDF15 or FGF21, respectively, resulting in marked reductions in body weight, epididymal fat mass, insulin resistance, and hepatic steatosis. In addition, GDF15 treatment led to early reduction in body weight despite no change in food intake, indicating the role of GDF15 other than appetite loss. GDF15 treatment increased liver-derived serum FGF21 levels, whereas FGF21 treatment did not affect GDF15 expression. GDF15 promoted eIF2α phosphorylation and XBP1 splicing, leading to FGF21 induction. In murine AML12 hepatocytes treated with free fatty acids (FFAs), GDF15 overexpression upregulated Fgf21 mRNA levels and promoted eIF2α phosphorylation and XBP1 splicing. Overall, continuous exposure to excess FFAs resulted in a gradual increase of β-oxidation-derived reactive oxygen species and endoplasmic reticulum stress, suggesting that GDF15 enhanced this pathway and induced FGF21 expression. GDF15- and FGF21-related crosstalk is an important pathway for the treatment of MASLD.

Abstract Recent studies indicate a potential link between oral health and cognitive function; however, long-term associations remain unclear. This study aimed to identify oral health factors that predict changes in cognitive function among older adults over time. The study included 583 independent older adults (201 male, 382 female) with a mean age of 72.7 years. Cognitive function was assessed using Mini-Mental State Examination (MMSE) at baseline and follow-up over two years, with relative change in MMSE (rMMSE) calculated. Baseline oral health variables included number of remaining teeth, masticatory performance, occlusal force, oral diadochokinesis and tongue pressure. Physical performance and confounding factors were also considered. The relationship between rMMSE and the variables was analyzed using Pearson’s correlation, Mann-Whitney U test, and multiple linear regression analysis. Cognitive function declined in 196 subjects, with rMMSE significantly correlated with oral diadochokinesis. Regression analysis revealed significant associations between cognitive changes and oral diadochokinesis (p = 0.020) and knee extension strength as a physical performance (p = 0.047). Our findings suggest that cognitive decline may be indicated by declines in both physical and oral motor performance. Incorporating oral diadochokinesis testing into health screenings could aid early detection of cognitive decline, improving outcomes and reducing healthcare burdens.

Abstract Calcium phosphate-based materials (CaP) are introduced as potential dental pulp capping materials for deciduous teeth. The present study investigated the influence of inorganic phosphate (Pi) on regulating stem cells isolated from human exfoliated deciduous teeth (SHED). SHEDs were treated with Pi. Cell cycle progression and apoptosis were examined using flow cytometry analysis. Osteo/odontogenic and adipogenic differentiation were analyzed using alizarin red S and oil red O staining, respectively. The mRNA expression profile was investigated using a high-throughput RNA sequencing technique. Pi increased the late apoptotic cell population while cell cycle progression was not altered. Pi upregulated osteo/odontoblastic gene expression and enhanced calcium deposition. Pi-induced mineralization was reversed by pretreatment of cells with Foscarnet, or p38 inhibitor. Pi treatment inhibited adipogenic differentiation as determined by decreased PPARγ expression and reduced intracellular lipid accumulation. Bioinformatic analysis of gene expression profiles demonstrated several involved pathways, including PI3K/AKT, MAPK, EGFR, and VEGF signaling. In conclusion, Pi enhanced osteo/odontogenic but inhibited adipogenic differentiation in SHED.

Abstract The platelet-derived growth factor (PDGF) family contributes to the progression of steatohepatitis; however, changes in and the characteristics of isoform-specific expression remain unclear. Since diabetes is a major driver of metabolic dysfunction-associated steatohepatitis (MASH), we characterized the mouse model of diabetic MASH (dMASH) by focusing on PDGF signaling. Pdgfa-d expression was markedly higher in hepatic stellate cells among flow-sorted cells in control mice and also increased in dMASH. In contrast, a reanalysis of human single-cell RNA-Seq data showed the distinct distribution of each PDGF isoform with disease progression. Furthermore, inflammation and fibrosis in the liver were less severe in diabetic MASH using tamoxifen-induced PDGF receptor β (PDGFRβ)-deficient mice (KO) than in control dMASH using floxed mice (FL) at 12 weeks old. Despite the absence of tumors, the expression of tumor-related genes was lower in KO than in FL. Tumorigenesis was significantly lower in 20-week-old KO. An Ingenuity Pathway Analysis of differentially expressed miRNA between FL and KO identified functional networks associated with hepatotoxicity and cancer. Therefore, PDGFRβ signals play important roles in the progression of steatohepatitis and tumorigenesis in MASH, with the modulation of miRNA expression posited as a potential underlying mechanism.

Abstract The effects of meteorological conditions on IOP using a large-scale health examination cohort were investigated. There were a total of 811,854 measurements from 126,630 eyes of 63,839 subjects in 9 years from a health checkup cohort followed up annually for age, sex, body height, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and IOP. The effects of these variables and the meteorological data of daily average temperature (TP), daily average local atmospheric pressure (AP), daily average volumetric humidity (VH), and daily amount of rainfall (RF) on the day of IOP measurement on IOP were investigated. Several variables were significantly associated with IOP, including sex, age, body height, BMI, SBP, DBP, average TP, average AP, average VH, RF, white blood cell count, red blood cell count, hemoglobin, aspartate aminotransferase, alanine aminotransferase, guanosine triphosphate, calcium, and HbA1c. This study indicated a correlation between meteorological factors and IOP. Higher AP and RF were associated with elevated IOP, whereas higher TP and VH were associated with decreased IOP.

Abstract Plant tendrils are specialized organs that can twine around other structures to facilitate climbing. They occur in a variety of plant families and have diverse ontogenic origins. In cucurbits, tendrils originate from lateral shoots. Fine mapping verified that the tendril-less ctl mutation of the melon Cucumis melo corresponds to a frameshift mutation in the CmTCP1 gene, which encodes a TCP transcription factor. A yeast two-hybrid screen for CmTCP1/CTL-interacting proteins identified a member of the plant-specific YABBY transcription factor family, which was named CmYAB1. Each of the N- and C-terminal regions of CmTCP1 interacted with CmYAB1. The ctl mutation impaired the interaction between CmTCP1 and CmYAB1. Both proteins interacted in vitro and were localized to the nucleus in plant cells. In situ expression analysis revealed the coexistence of the CmTCP1 and CmYAB1 mRNAs in the abaxial domains of developing tendrils. An RNA-seq analysis of the seven YABBY genes in the melon genome revealed relatively high expression ratios of CmYAB1 in tendrils compared with those in leaves. These results suggest a novel function of the YABBY protein through its interaction with a TCP protein in the development of cucurbit tendrils.

Abstract The reflexive excitation of the sympathetic nervous system in response to psychological stress leads to elevated blood pressure, a condition that persists even after the stress has been alleviated. This sustained increase in blood pressure, which may contribute to the pathophysiology of hypertension, could be linked to neural plasticity in sympathetic nervous activity. Given the critical role of astrocytes in various forms of neural plasticity, we investigated their involvement in maintaining elevated blood pressure during the post-stress phase. Specifically, we examined the effects of arundic acid, an astrocytic inhibitor, on blood pressure and heart rate responses to air-jet stress. First, we confirmed that the inhibitory effect of arundic acid is specific to astrocytes. Using c-Fos immunohistology, we then observed that psychological stress activates neurons in cardiovascular brain regions, and that this stress-induced neuronal activation was suppressed by arundic acid pre-treatment in rats. By evaluating astrocytic process thickness, we also confirmed that astrocytes in the cardiovascular brain regions were activated by stress, and this activation was blocked by arundic acid pre-treatment. Next, we conducted blood pressure measurements on unanesthetized, unrestrained rats. Air-jet stress elevated blood pressure, which remained high for a significant period during the post-stress phase. However, pre-treatment with arundic acid, which inhibited astrocytic activation, suppressed stress-induced blood pressure elevation both during and after stress. In contrast, arundic acid had no significant impact on heart rate. These findings suggest that both neurons and astrocytes play integral roles in stress-induced blood pressure elevation and its persistence after stress, offering new insights into the pathophysiological mechanisms underlying hypertension.

Abstract The antigen-mediated B cell isolation method, based on the detection of surface IgG (sIgG), has increased the efficiency of therapeutic antibody (Ab) discovery. However, the reduction in sIgG expression on B cells during plasma cell differentiation presents challenges as it enables Ab production from only a small subset of B cells (e.g., memory B cells). The present study aimed to addressed this problem by developing a workflow to isolate human-IgG-secreting hybridoma cells produced by cell fusion, the majority of which express sIgG. We showed that our sIgG-based antigen-coated bead separation method efficiently enriched hybridoma cells expressing antigen-specific Abs with a yield of 83.5% (from the cell fusion pool) and a positive rate of 73.2%. Furthermore, because the separation could be performed after only a short (1–2-day) culture period following cell fusion, diverse hybridoma clones could be obtained, minimizing clonal selection and the incidence of duplicates. Given that the expression of membrane-bound IgG and sIgG are regulated by different splicing mechanisms, we speculate that the cell fusion step potentially attenuated the suppression of human sIgG expression. Overall, our proposed method is expected to markedly improve the efficiency of therapeutic Ab candidate production, which will have important clinical implications.

Abstract Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P

Abstract Assessing intraoperative hemodynamics with Surgical Apgar Score (SAS) and preoperative nutritional status with the Controlling Nutritional Status (CONUT) score are said to be useful to predict postoperative complications in many surgical services, but little is reported in the field of spinal surgery. The purpose of this study was to assess the utility of SAS and the CONUT score for predicting the risk of major postoperative complications after spinal surgery. We included 659 people who undergone spinal surgery in our institute in eight consecutive years. The occurrence of postoperative major complications was investigated. Background clinical information, surgical information including the SAS and the CONUT score, and the length of postoperative hospital stay were collected. The risk factors of postoperative complications were assessed statistically. Complications occurred in 117 cases (17.8%). The multivariate analysis showed that history of diabetes mellitus (odds ratio [OR] 1.81: P = 0.035), coronary disease (OR 3.33; P = 0.009), American Society of Anesthesiologists Physical Status (OR 1.71; P = 0.025), use of instruments (OR 2.07; P = 0.026), operation time (OR 1.30; P

Abstract G9a is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9 (H3K9), which is involved in the regulation of gene expression. We had previously reported that G9a is expressed in developing tendons in vivo and in vitro and that G9a-deficient tenocytes show impaired proliferation and differentiation in vitro. In this study, we investigated the functions of G9a in tendon development in vivo by using G9a conditional knockout (G9a cKO) mice. We crossed Sox9 Cre/+ mice with G9a fl/fl mice to generate G9a fl/fl ; Sox9 Cre/+ mice. The G9a cKO mice showed hypoplastic tendon formation at 3 weeks of age. Bromodeoxyuridine labeling on embryonic day 16.5 (E16.5) revealed decreased cell proliferation in the tenocytes of G9a cKO mice. Immunohistochemical analysis revealed decreased expression levels of G9a and its substrate, H3K9me2, in the vertebral tendons of G9a cKO mice. The tendon tissue of the vertebrae and limbs of G9a cKO mice showed reduced expression of a tendon marker, tenomodulin (Tnmd), and col1a1 genes, suggesting that tenocyte differentiation was suppressed. Overexpression of G9a resulted in enhancement of Tnmd and col1a1 expression in tenocytes in vitro. These results suggest that G9a regulates the proliferation and differentiation of tendon progenitor cells during tendon development. Thus, our results suggest that G9a plays an essential role in tendon development.

Abstract This study aims to investigate the influence of lumbar spine disorders on the development of asymmetric hallux valgus (HV). Data from the fifth survey of the Osteoarthritis/Osteoporosis Against Disability (ROAD) study, a nationwide prospective study in Japan, were analyzed. HV severity was categorized into 4 grades based on the radiographic HV angle, and asymmetric HV was defined as having at least one HV on either side, with a difference of two or more severity grades between the left and right. Controls were matched from both the Normal group (without HV on both sides) and the Symmetric group (HV on at least one side with a difference of one or less severity grades). Univariate analysis assessed lumbar conditions, and multinomial logistic regression analysis explored the association between lumbar spine disorders and asymmetric HV. Among 1997 participants, 27 had asymmetric HV. Univariate analysis revealed a higher incidence of L5 spondylolisthesis and scoliosis in the Asymmetric group. Multinomial logistic regression analysis revealed that scoliosis independently increased the likelihood of asymmetrical HV (Odds ratio [OR] = 3.586, 95%Confidence interval [CI] 1.111–11.582), but showed no significant impact on symmetrical HV (OR 0.910, 95% CI 0.355–2.334). Asymmetric HV is rare but may be associated with lumbar spine disorders, particularly scoliosis.

Abstract Osteoporosis, vertebral fractures, and spinal degenerative diseases are common conditions that often coexist in older adults. This study aimed to determine the factors influencing low back pain and its impact on activities of daily living (ADL) and physical performance in older individuals with multiple comorbidities. This cross-sectional study was part of a large-scale population-based cohort study in Japan, involving 1009 participants who underwent spinal magnetic resonance imaging (MRI) to assess cervical cord compression, radiographic lumbar spinal stenosis, and lumbar disc degeneration. Vertebral fractures in the thoracolumbar spine were evaluated using sagittal MRI with a semi-quantitative method. Bone mineral density was measured using dual-energy X-ray absorptiometry. Low back pain, Oswestry Disability Index (ODI), and physical performance tests, such as one-leg standing time, five times chair-stand time, maximum walking speed, and maximum step length, were assessed. Using clinical conditions as objective variables and image evaluation parameters as explanatory variables, multiple regression analysis showed that vertebral fractures were significantly associated with low back pain and ODI. Vertebral fractures and osteoporosis significantly impacted physical performance, whereas osteoporosis alone did not affect low back pain or ODI. Our findings contribute to new insights into low back pain and its impact on ADL and physical performance.

Abstract Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted in seven individuals with early-stage ALS. Participants were given 3 months of home-based resistance exercise focusing on the quadriceps muscles. The strength of exercised muscle was evaluated using bilateral quadriceps strength with manual muscle testing, handheld dynamometers, five times sit-to-stand, and Timed-Up-and-Go before and after the exercise program. In addition, changes in the Sickness Impact Profile ALS-19 (SIP/ALS-19) as the functional outcome measure and the transcriptome of exercised muscles were compared before and after the exercise. The primary outcome of muscle strength did not change significantly by the exercise program. The exercise program maintained the SIP/ALS-19 and the ALS Functional Rating Scale-Revised (ALSFRS-R). Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including parvalbumin. Three months of moderately intense strength and conditioning exercise maintained muscle strength of the exercised muscle and ALSFRS-R scores and had a positive effect on patients’ muscle transcriptome.

Abstract Automation and quality control (QC) are critical in manufacturing safe and effective cell and gene therapy products. However, current QC methods, reliant on molecular staining, pose difficulty in in-line testing and can increase manufacturing costs. Here we demonstrate the potential of using label-free ghost cytometry (LF-GC), a machine learning-driven, multidimensional, high-content, and high-throughput flow cytometry approach, in various stages of the cell therapy manufacturing processes. LF-GC accurately quantified cell count and viability of human peripheral blood mononuclear cells (PBMCs) and identified non-apoptotic live cells and early apoptotic/dead cells in PBMCs (ROC-AUC: area under receiver operating characteristic curve = 0.975), T cells and non-T cells in white blood cells (ROC-AUC = 0.969), activated T cells and quiescent T cells in PBMCs (ROC-AUC = 0.990), and particulate impurities in PBMCs (ROC-AUC ≧ 0.998). The results support that LF-GC is a non-destructive label-free cell analytical method that can be used to monitor cell numbers, assess viability, identify specific cell subsets or phenotypic states, and remove impurities during cell therapy manufacturing. Thus, LF-GC holds the potential to enable full automation in the manufacturing of cell therapy products with reduced cost and increased efficiency.

Abstract Age-related macular degeneration (AMD) is associated with the dysfunction and degeneration of retinal pigment epithelium (RPE) cells. Here, we examined how the formation and expansions of cell clusters are regulated by the differentiation of the RPE cells. In this study, ARPE-19 cells were cultivated in standard or differentiation media, i.e., without or with nicotinamide, to evaluate the spreading of cell clusters specified with differentiated cell phenotypes. Mitochondria membrane potential (MMP) and the distribution of the RPE cell clusters was also monitored with or without rotenone, a mitochondrial electron transport chain (ETC) complex I inhibitor. Cultured ARPE-19 cells generated scattered cell clusters composed mostly of smaller size cells expressing the differentiation markers mouse anti-cellular retinaldehyde–binding protein (CRALBP) and Bestrophin only in differentiation medium. After the increase of the number of clusters, the clusters appeared to paracellularly merge, resulting in expansion of the area occupied by the clusters. Of note, the cells within the clusters selectively had high MMP and were in accordance with the expression of RPE differentiation markers. Rotenone repressed the formation of the clusters and decreased intracellular MMP. The above results suggest that clustering of RPE cells with functional mitochondria plays a pivotal role in RPE cell differentiation process and the ETC complex I inhibition greatly influences the composition of RPE cells that are degenerated or differentiation disposed.

Abstract Previous studies have shown that rapid on-site evaluation (ROSE) improves the diagnostic yield of bronchoscopy using endobronchial ultrasound with a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPL). While ROSE of imprint cytology from forceps biopsy has been widely discussed, there are few reports on ROSE of brush cytology. This study investigated the utility of ROSE of brush cytology during bronchoscopy. We retrospectively analyzed data from 214 patients who underwent bronchoscopy with EBUS-GS for PPL. The patients in the ROSE group had significantly higher diagnostic sensitivity through the entire bronchoscopy process than in the non-ROSE group (96.8% vs. 83.3%, P = 0.002). The use of ROSE significantly increased the sensitivity of brush cytology with Papanicolaou staining (92.9% vs. 75.0%, P

Abstract Cinema, a modern titan of entertainment, holds power to move people with the artful manipulation of auditory and visual stimuli. Despite this, the mechanisms behind how sensory stimuli elicit emotional responses are unknown. Thus, this study evaluated which brain regions were involved when sensory stimuli evoke auditory- or visual-driven emotions during film viewing. Using functional magnetic resonance imaging (fMRI) decoding techniques, we found that brain activities in the auditory area and insula represent the stimuli that evoke emotional response. The observation of brain activities in these regions could provide further insights to these mechanisms for the improvement of film-making, as well as the development of novel neural techniques in neuroscience. In near feature, such a “neuro-designed” products/ applications might gain in popularity.

Abstract Colonoscopies are widely available, but there are cases where insertion can be difficult, even for experienced endoscopists. EC-760XP/L, a new ultrasmall-diameter long scope, may be useful in such cases. This single-center retrospective study included 39 cases where colonoscope insertion was difficult even when previously conducted by an experienced endoscopist. The primary outcome was the cecal intubation time using EC-760XP/L compared to the time used in a previous examination with a standard scope. The secondary outcomes were the cecum intubation rate, intestinal cleanliness level, adenoma detection rate, polyp detection rate, sedative use rate, occurrence of adverse events, and pain experience. A comparison of cecal intubation times between EC-760XP/L and the standard scope showed that insertion times were significantly lower with EC-760XP/L (9.5 min) compared to the standard scope (19 min) (p

Abstract This retrospective cohort study aimed to investigate the association between alcohol consumption and the onset of type 2 diabetes in middle-aged Japanese individuals. Participants were aged 40 and above from Panasonic Corporation, Osaka, Japan’s medical health checkup program from 2008 to 2021. Alcohol consumption was calculated by converting the quantity consumed into daily ethanol consumption. We assessed the association between alcohol consumption and the onset of type 2 diabetes using Cox regression analysis. The total and median follow-up duration was 13 years and 7 (3–13) years (748,090 person-years). Among 102,802 participants, 7,510 participants (7.3%) developed type 2 diabetes during the study period. Alcohol consumption at the level of 0

Abstract Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.

Abstract Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS.

Abstract Epithelial ovarian cancer (EOC) is widely recognized as the most lethal gynecological malignancy; however, its early-stage detection remains a considerable clinical challenge. To address this, we have introduced a new method, named Comprehensive Serum Glycopeptide Spectral Analysis (CSGSA), which detects early-stage cancer by combining glycan alterations in serum glycoproteins with tumor markers. We detected 1712 glycopeptides using liquid chromatography–mass spectrometry from the sera obtained from 564 patients with EOC and 1149 controls across 13 institutions. Furthermore, we used a convolutional neural network to analyze the expression patterns of the glycopeptides and tumor markers. Using this approach, we successfully differentiated early-stage EOC (Stage I) from non-EOC, with an area under the curve (AUC) of 0.924 in receiver operating characteristic (ROC) analysis. This method markedly outperforms conventional tumor markers, including cancer antigen 125 (CA125, 0.842) and human epididymis protein 4 (HE4, 0.717). Notably, our method exhibited remarkable efficacy in differentiating early-stage ovarian clear cell carcinoma from endometrioma, achieving a ROC-AUC of 0.808, outperforming CA125 (0.538) and HE4 (0.557). Our study presents a promising breakthrough in the early detection of EOC through the innovative CSGSA method. The integration of glycan alterations with cancer-related tumor markers has demonstrated exceptional diagnostic potential.

Abstract The influence of pulmonary dysfunction on postoperative outcomes in older patients with gastric cancer was assessed. In this retrospective study, 352 older patients (age ≥ 75 years) with gastric cancer who underwent preoperative spirometry and curative gastrectomy were enrolled. Of these patients, 200 underwent laparoscopic gastrectomy. Restrictive and obstructive pulmonary dysfunction were defined as percentage of vital capacity (%VC)

Abstract Abnormal brain aging is suggested in epilepsy. Given the brain network dysfunction in epilepsy, the white matter tracts, which primarily interconnect brain regions, could be of special importance. We focused on white matter brain aging in diverse forms of epilepsy and comorbid psychosis. We obtained brain diffusion tensor imaging (DTI) data at 3 T-MRI in 257 patients with epilepsy and 429 healthy subjects. The tract-based fractional anisotropy values of the healthy subjects were used to build a brain-age prediction model, and we calculated the brain-predicted age difference (brain-PAD: predicted age—chronological age) of all subjects. As a result, almost all epilepsy categories showed significantly increased brain-PAD (p

Abstract Pulmonary fibrosis is a progressive disease caused by interstitial inflammation. Treatments are extremely scarce; therapeutic drugs and transplantation therapies are not widely available due to cost and a lack of donors, respectively. Recently, there has been a high interest in regenerative medicine and exponential advancements in stem cell-based therapies have occurred. However, a sensitive imaging technique for investigating the in vivo dynamics of transplanted stem cells has not yet been established and the mechanisms of stem cell-based therapy remain largely unexplored. In this study, we administered mouse adipose tissue-derived mesenchymal stem cells (mASCs) labeled with quantum dots (QDs; 8.0 nM) to a mouse model of bleomycin-induced pulmonary fibrosis in an effort to clarify the relationship between in vivo dynamics and therapeutic efficacy. These QD-labeled mASCs were injected into the trachea of C57BL/6 mice seven days after bleomycin administration to induce fibrosis in the lungs. The therapeutic effects and efficacy were evaluated via in vivo/ex vivo imaging, CT imaging, and H&E staining of lung sections. The QD-labeled mASCs remained in the lungs longer and suppressed fibrosis. The 3D imaging results showed that the transplanted cells accumulated in the peripheral and fibrotic regions of the lungs. These results indicate that mASCs may prevent fibrosis. Thus, QD labeling could be a suitable and sensitive imaging technique for evaluating in vivo kinetics in correlation with the efficacy of cell therapy.

Abstract Peripheral nerve injury (PNI) often leads to retrograde cell death in the spinal cord and dorsal root ganglia (DRG), hindering nerve regeneration and functional recovery. Repetitive magnetic stimulation (rMS) promotes nerve regeneration following PNI. Therefore, this study aimed to investigate the effects of rMS on post-injury neuronal death and nerve regeneration. Seventy-two rats underwent autologous sciatic nerve grafting and were divided into two groups: the rMS group, which received rMS and the control (CON) group, which received no treatment. Motor neuron, DRG neuron, and caspase-3 positive DRG neuron counts, as well as DRG mRNA expression analyses, were conducted at 1-, 4-, and 8-weeks post-injury. Functional and axon regeneration analyses were performed at 8-weeks post-injury. The CON group demonstrated a decreased DRG neuron count starting from 1 week post-injury, whereas the rMS group exhibited significantly higher DRG neuron counts at 1- and 4-weeks post-injury. At 8-weeks post-injury, the rMS group demonstrated a significantly greater myelinated nerve fiber density in autografted nerves. Furthermore, functional analysis showed significant improvements in latency and toe angle in the rMS group. Overall, these results suggest that rMS can prevent DRG neuron death and enhance nerve regeneration and motor function recovery after PNI.

Abstract The global challenge of on-site detection of highly enriched uranium (HEU), a substance with considerable potential for unauthorized use in nuclear security, is a critical concern. Traditional passive nondestructive assay (NDA) techniques, such as gamma-ray spectroscopy with high-purity germanium detectors, face significant challenges in detecting HEU when it is shielded by heavy metals. Addressing this critical security need, we introduce an on-site detection method for lead-shielded HEU employing a transportable NDA system that utilizes the 252Cf rotation method with a water Cherenkov neutron detector. This cost-effective NDA system is capable of detecting 4.17 g of 235U within a 12 min measurement period using a 252Cf source of 3.7 MBq. Integrating this system into border control measures can enhance the prevention of HEU proliferation significantly and offer robust deterrence against nuclear terrorism.

Abstract Recent advances in AI and intelligent vehicle technology hold the promise of revolutionizing mobility and transportation through advanced driver assistance systems (ADAS). Certain cognitive factors, such as impulsivity and inhibitory control have been shown to relate to risky driving behavior and on-road risk-taking. However, existing systems fail to leverage such factors in assistive driving technologies adequately. Varying the levels of these cognitive factors could influence the effectiveness and acceptance of ADAS interfaces. We demonstrate an approach for personalizing driver interaction via driver safety interfaces that are are triggered based on the inference of the driver’s latent cognitive states from their driving behavior. To accomplish this, we adopt a data-driven approach and train a recurrent neural network to infer impulsivity and inhibitory control from recent driving behavior. The network is trained on a population of human drivers to infer impulsivity and inhibitory control from recent driving behavior. Using data collected from a high-fidelity vehicle motion simulator experiment, we demonstrate the ability to deduce these factors from driver behavior. We then use these inferred factors to determine instantly whether or not to engage a driver safety interface. This approach was evaluated using leave-one-out cross validation using actual human data. Our evaluations reveal that our personalized driver safety interface that captures the cognitive profile of the driver is more effective in influencing driver behavior in yellow light zones by reducing their inclination to run through them.

Abstract Color centers in wide band-gap semiconductors, which have superior quantum properties even at room temperature and atmospheric pressure, have been actively applied to quantum sensing devices. Characterizing the quantum properties of the color centers in the semiconductor materials and ensuring that these properties are uniform over a wide area are key issues for developing quantum sensing devices based on color centers. In this article, we have developed an optics design protocol optimized for evaluating the quantum properties of color centers and have used this design approach to develop a new microscopy system called columnar excitation fluorescence microscope (CEFM). The essence of this system is to maximize the amount of fluorescence detection of polarized color centers, which is achieved by large-volume and uniform laser excitation along the sample thickness with sufficient laser power density. This laser excitation technique prevents undesirable transitions to undesirable charge states and undesirable light, such as unpolarized color center fluorescence, while significantly increasing the color center fluorescence. This feature enables fast measurements with a high signal-to-noise ratio, making it possible to evaluate the spatial distribution of quantum properties across an entire mm-size sample without using a darkroom, which is difficult with typical confocal microscope systems.

Abstract The pharynx is one of the few areas in the body where blood vessels and immune tissues can readily be observed from outside the body non-invasively. Although prior studies have found that sex could be identified from retinal images using artificial intelligence, it remains unknown as to whether individuals’ sex could also be identified using pharyngeal images. Demographic information and pharyngeal images were collected from patients who visited 64 primary care clinics in Japan for influenza-like symptoms. We trained a deep learning-based classification model to predict reported sex, which incorporated a multiple instance convolutional neural network, on 20,319 images from 51 clinics. Validation was performed using 4869 images from the remaining 13 clinics not used for the training. The performance of the classification model was assessed using the area under the receiver operating characteristic curve. To interpret the model, we proposed a framework that combines a saliency map and organ segmentation map to quantitatively evaluate salient regions. The model achieved the area under the receiver operating characteristic curve of 0.883 (95% CI 0.866–0.900). In subgroup analyses, a substantial improvement in classification performance was observed for individuals aged 20 and older, indicating that sex-specific patterns between women and men may manifest as humans age (e.g., may manifest after puberty). The saliency map suggested the model primarily focused on the posterior pharyngeal wall and the uvula. Our study revealed the potential utility of pharyngeal images by accurately identifying individuals’ reported sex using deep learning algorithm.