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Abstract We propose a hybrid inflationary scenario based on eight-flavor hidden QCD with the hidden colored fermions being in part gauged under U(1) B−L . This hidden QCD is almost scale-invariant, so-called walking, and predicts the light scalar meson (the walking dilaton) associated with the spontaneous scale breaking, which develops the Coleman-Weinberg (CW) type potential as the consequence of the nonperturbative scale anomaly, hence plays the role of an inflaton of the small-field inflation. The U(1) B−L Higgs is coupled to the walking dilaton inflaton, which is dynamically induced from the so-called bosonic seesaw mechanism. We explore the hybrid inflation system involving the walking dilaton inflaton and the U(1) B−L Higgs as a waterfall field. We find that observed inflation parameters tightly constrain the U(1) B−L breaking scale as well as the walking dynamical scale to be ~ 109 GeV and ~ 1014 GeV, respectively, so as to make the waterfall mechanism worked. The lightest walking pion mass is then predicted to be around 500 GeV. Phenomenological perspectives including embedding of the dynamical electroweak scalegenesis and possible impacts on the thermal leptogenesis are also addressed.

Glioblastoma (GBM) is the central nervous system tumor with the most aggressive behavior, and no definitive therapy has yet been found. The tumor microenvironment of GBM is immunosuppressive and is considered a ‘cold tumor’ with low lymphocytic infiltration, but is characterized by a high proportion of glioma-associated macrophages/microglia (GAMs). GAMs promote tumor growth and also affect treatment resistance in GBM. In this review, we describe the origin and classification of GAMs in humans and describe the mechanisms of their activation and the cell-cell interactions between tumor cells and GAMs. We also describe the history of GAM detection methods, especially immunohistochemistry, and discusses the merits and limitations of these techniques. In addition, we summarized chemotactic factors for GAMs and the therapies targeting these factors. Recent single-cell RNA analysis and spatial analysis add new insights to our previous knowledge of GAMs. Based on these studies, GBM therapies targeting GAMs are expected to be further developed.

Background/purpose: Sphingosine-1-phosphate (S1P) exhibits receptor-mediated physiological effects by facilitating the differentiation of mesenchymal stem cells toward the osteoblast lineage. This study aimed to determine the effect of S1P on odontogenic differentiation of mouse immortalized stem cells of dental apical papilla (iSCAP) and assess the distribution of the S1P receptor 1 (S1PR1) in the apical papilla and the root canal wall of immature rat molars. Materials and methods: Immunostaining for S1PR1 was conducted at the apex of the rat mandibular first molar and within the root canal wall. The iSCAP was treated with S1P and bone morphogenetic protein (BMP)-9 (for comparison), and the expression levels of the odontogenic differentiation marker were evaluated via real-time reverse-transcriptase quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Mineralization and lipid droplet formation were evaluated via Alizarin red and Oil red O staining. Results: S1PR1-positive cells were expressed in areas of both apical papilla and dentin-pulp interface of root canal wall. During the odontogenic differentiation of iSCAP, S1P and BMP-9 increased the expression of the differentiation marker mRNA and secreted proteins including dentin sialophosphoprotein, dentin matrix phosphoprotein 1, and matrix extracellular phosphoglycoprotein. The S1PR1 signaling pathway is involved in the action of S1P, but not that of BMP-9. S1PR1 signaling also facilitated mineralization in iSCAP and suppressed the differentiation of these cells into adipocytes. Conclusion: S1P induced odontogenic differentiation of iSCAP through S1PR1. Furthermore, S1PR1-positive cells were expressed in the apical papilla of immature rat molars and in the dentin-pulp interface where odontoblast-like cells exist.

Abstract The electroweak (EW) phase transition in the early Universe might be supercooled due to the presence of the classical scale invariance involving Beyond the Standard Model (BSM) sectors and the supercooling could persist down till a later epoch around which the QCD chiral phase transition is supposed to take place. Since this supercooling period keeps masslessness for all the six SM quarks, it has simply been argued that the QCD phase transition is the first order, and so is the EW one. However, not only the QCD coupling but also the top Yukawa and the Higgs quartic couplings get strong at around the QCD scale due to the renormalization group running, hence this scenario is potentially subject to a rigorous nonperturbative analysis. In this work, we employ the ladder Schwinger-Dyson (LSD) analysis based on the Cornwall-Jackiw-Tomboulis formalism at the two-loop level in such a gauge-Higgs-Yukawa system. We show that the chiral broken QCD vacuum emerges with the nonperturbative top condensate and the lightness of all six quarks is guaranteed due to the accidental U(1) axial symmetry presented in the top-Higgs sector. We employ a quark-meson model-like description in the mean field approximation to address the impact on the EW phase transition arising due to the top quark condensation at the QCD phase transition epoch. In the model, the LSD results are encoded to constrain the model parameter space. We then observe the cosmological phase transition of the first-order type and discuss the induced gravitational wave (GW) productions. We find that in addition to the conventional GW signals sourced from an expected BSM at around or over the TeV scale, the dynamical topponium-Higgs system can yield another power spectrum sensitive to the BBO, LISA, and DECIGO, etc.

Abstract Background Although involvement of toddlers in swimming activities has increased recently, information regarding the impact of swimming during toddlerhood on subsequent child motor competence development is scarce. This study aimed to determine how swimming experience, particularly the timing of initiation and the continuity of swimming activities up to the age of 3 years, affects motor competence development. Methods This prospective cohort study included data on children aged 1.5 and 3 years (100,286 mother–child pairs) from the Japan Environment and Children’s Study. The outcomes measured were gross and fine motor function, using the Japanese version of the Ages and Stages Questionnaire (Third edition). We assessed how these functions correlated with the continuous pattern of swimming pool use frequency from age 1 up to 3 years. Results The group that used a swimming pool once a month or more from age 1–1.5 years but stopped from age 2–3 years showed consistently significant negative associations with gross motor development delay (minimum adjusted odds ratio [aOR]: 0.66, 95% confidence interval [CI]: 0.60–0.73) and fine motor development delay (minimum aOR: 0.66, 95% CI: 0.58–0.76). The group that continued swimming once a month or more from age 1–3 years showed consistently significant negative associations with gross motor development delay (minimum aOR: 0.64, 95% CI: 0.54–0.75) and fine motor development delay (minimum aOR: 0.42, 95% CI: 0.31–0.55). Conclusions These results suggest that swimming experience starting around age 1 year is positively associated with gross and fine motor function development. The beneficial impact on gross motor function persisted from age 1–3 years. In contrast, the effects on fine motor function were not evident until age ≥ 2.5 years after starting swimming at approximately age 1 year. These findings underscore the potential benefits of early swimming experiences in enhancing overall motor skills development during early childhood.

Abstract The transplantation of human mesenchymal stromal/stem cells (hMSCs) has potential as a curative and permanent therapy for congenital skeletal diseases. However, the self-renewal and differentiation capacities of hMSCs markedly vary. Therefore, cell proliferation and trilineage differentiation capacities were tested in vitro to characterize hMSCs before their clinical use. However, it remains unclear whether the ability of hMSCs in vitro accurately predicts that in living animals. The xenograft model is an alternative method for validating clinical MSCs. Nevertheless, the protocol still needs refinement, and it has yet to be established whether hMSCs, which are expanded in culture for clinical use, retain the ability to engraft and differentiate into adipogenic, osteogenic, and chondrogenic lineage cells in transplantation settings. In the present study, to establish a robust xenograft model of MSCs, we examined the delivery routes of hMSCs and the immunological state of recipients. The intra-arterial injection of hMSCs into X-ray-irradiated (IR) NOG, a severely immunodeficient mouse, achieved the highest engraftment but failed to sustain long-term engraftment. We demonstrated that graft cells localized to a collagenase-released fraction (CR), in which endogenous colony-forming cells reside. We also showed that Pdgfrα+Sca1+ MSCs (PαS), which reside in the CR fraction, resisted IR. These results show that our protocol enables hMSCs to fulfill a high level of engraftment in mouse bone marrow in the short term. In contrast, long-term reconstitution was restricted, at least partially, because of IR-resistant endogenous MSCs.

Abstract Genetically encoded fluorescent sensors continue to be developed and improved. If they could be expressed across multiple cortical areas in non-human primates, it would be possible to measure a variety of spatiotemporal dynamics of primate-specific cortical activity. Here, we develop an Automated Robotic Virus injection System (ARViS) for broad expression of a biosensor. ARViS consists of two technologies: image recognition of vasculature structures on the cortical surface to determine multiple injection sites without hitting them, and robotic control of micropipette insertion perpendicular to the cortical surface with 50 μm precision. In mouse cortex, ARViS sequentially injected virus solution into 100 sites over a duration of 100 min with a bleeding probability of only 0.1% per site. Furthermore, ARViS successfully achieved 266-site injections over the frontoparietal cortex of a female common marmoset. We demonstrate one-photon and two-photon calcium imaging in the marmoset frontoparietal cortex, illustrating the effective expression of biosensors delivered by ARViS.

Abstract Formation of a single crystalline oxide semiconductor on an insulating film as a channel material capable of three-dimensional (3D) stacking would enable 3D very-large-scale integration circuits. This study presents a technique for forming single-crystalline In2O3 having no grain boundaries in a channel formation region on an insulating film using the (001) plane of c-axis-aligned crystalline indium gallium zinc oxide as a seed. Vertical field-effect transistors using the single-crystalline In2O3 had an off-state current of 10−21 A μm−1 and electrical characteristics were improved compared with those using non-single-crystalline In2O3: the subthreshold slope was improved from 95.7 to 86.7 mV dec.−1, the threshold voltage showing normally-off characteristics (0.10 V) was obtained, the threshold voltage standard deviation was improved from 0.11 to 0.05 V, the on-state current was improved from 22.5 to 28.8 μA, and a 17-digit on/off ratio was obtained at 27 °C.

Abstract The most common age constraint for the diatomaceous sediments is biostratigraphy of siliceous microfossils. Although biostratigraphy is a powerful tool to establish stratigraphy and correlate with sedimentary sequences in other sites, biostratigraphy generally includes uncertainties difficult to evaluate. In this study, we measured zircon U–Pb ages of eight tuff beds intercalated with diatomaceous mudstone of the Nakayama Formation on Sado Island in Central Japan and integrated the U–Pb ages with diatom and radiolarian biostratigraphy, whose ages and errors were re-evaluated by this study, to establish an age model precisely representing the sedimentary age. Two tuff beds in the upper and middle part of the formation offered zircon U–Pb ages of 6.7 ± 0.2 Ma and 10.87 ± 0.07 Ma, which are consistent with biostratigraphy, and provided a good example of effective integration of zircon U–Pb ages with the biostratigraphy. On the other hand, zircon U–Pb ages of the other six tuff beds in the lower part are around 12 Ma and not distinguishable from each other. In addition, older zircon grains in the 6 tuff beds are assembled in the interval from 30 to 20 Ma, which is consistent with the age of the volcanic basement rocks forming most part of Sado Island. Similarities in chemical compositions of glass shards and age distributions of zircon grains indicate that the volcaniclastic components in the tuff beds should originate from single or associated magmatic activities.