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During the development of the mouse dentate gyrus (DG), granule neuronal progenitors (GNPs) arise from glial fibrillary acidic protein (GFAP)-expressing neural stem cells in the dentate notch. However, the transcriptional regulators that control their stepwise differentiation remain poorly defined. Since neurogenesis involves epithelial-to-mesenchymal transition (EMT)-like processes, we investigated the spatio-temporal expression profiles of the EMT transcription factors Zeb1, Scratch2 (Scrt2) and Nkx6-2 in relation to known GNP markers. Our results show that Zeb1 and Scrt2 exhibit sequential, but partially overlapping expression across embryonic and postnatal stages of GNP differentiation. Zeb1 is highly enriched in gfap -GFP+/Sox2+ neural stem/progenitor pools and subsets of Tbr2+/Prox1+/NeuroD+ intermediate GNPs, whereas Scrt2 predominates in Tbr2+/Prox1+/NeuroD+ GNPs. Strikingly, the neuronal EMT regulator Nkx6-2 shows selective expression in postnatal Tbr2+/Prox1+ GNPs, but it is excluded from embryonic counterparts. This temporally coordinated yet distinct expression of Zeb1, Scrt2 and Nkx6-2 reveals discrete transcriptional programs orchestrating GNP differentiation and neurogenic progression at embryonic versus postnatal stages of DG neurogenesis.

Astrocytes are key components of the neurovascular unit. While we have recently identified Olig2+ astrocyte progenitors (ASPs) in the developing mouse dentate gyrus (DG), their molecular signature remains incompletely characterized. Here we demonstrate that Olig2+ ASPs predominantly express brain lipid-binding protein (BLBP), while only a small population of them expresses gfap -GFP. These Olig2+/BLBP+ ASPs co-express the transcription factors Sox3, Sox9 and the proteoglycan NG2 but not Sox10, a marker for oligodendrocyte progenitors (OLPs). Olig2+ ASPs appear from embryonic day 18 (E18) onwards and decline at postnatal day 14 (P14). Consistent with the proliferation of both Olig2+ and NG2+ glial cells after brain injury, intrauterine intermittent hypoxia (IH) led to an increase in Olig2+/NG2+/BLBP+ ASPs in the postnatal DG. IH also promoted both angiogenesis and vascular coupling of Olig2+/NG2+ ASPs. Our data suggest that IH-induced expression of HIF1a increases Olig2+/NG2+/BLBP+ ASPs in a cell non-autonomous manner. Our data also revealed increased vascular coupling of GFAP+ astrocytes following IH, while the number of GFAP+ astrocytes remains unchanged. Given that BLBP, Olig2 and NG2 are expressed in reactive astrocytes, our findings suggest that Olig2+/NG2+/BLBP+ ASPs represent a subtype of reactive astrocyte progenitors. Furthermore, the enhanced vascular coupling of Olig2+/NG2+/BLBP+ ASPs appears to be an adaptive response to hypoxic brain injury. This study provides new insights into the molecular characteristics of Olig2+/NG2+/BLBP+ ASPs and their potential role in the brain’s response to hypoxic injury, contributing to our understanding of neurovascular unit dynamics in both development and pathological conditions.

We employed a multivalent peptide-library screening technique to identify a peptide motif that binds to phosphatidic acid (PA), but not to other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). A tetravalent peptide with the sequence motif of MARWHRHHH, designated as PAB-TP (phosphatidic acid-binding tetravalent peptide), was shown to bind as low as 1 mol% of PA in the bilayer membrane composed of PC and cholesterol. Kinetic analysis of the interaction between PAB-TP and the membranes containing 10 mol% of PA showed that PAB-TP associated with PA with a low dissociation constant of KD = 38 ± 5 nM. Coexistence of cholesterol or PE with PA in the membrane enhanced the PAB-TP binding to PA by increasing the ionization of the phosphomonoester head group as well as by changing the microenvironment of PA molecules in the membrane. Amino acid replacement analysis demonstrated that the tryptophan residue at position 4 of PAB-TP was involved in the interaction with PA. Furthermore, a series of amino acid substitutions at positions 5 to 9 of PAB-TP revealed the involvement of consecutive histidine and arginine residues in recognition of the phosphomonoester head group of PA. Our results demonstrate that the recognition of PA by PAB-TP is achieved by a combination of hydrophobic, electrostatic and hydrogen-bond interactions, and that the tetravalent structure of PAB-TP contributes to the high affinity binding to PA in the membrane. The novel PA-binding tetravalent peptide PAB-TP will provide insight into the molecular mechanism underlying the recognition of PA by PA-binding proteins that are involved in various cellular events.

One of the primary goals of Hayabusa2 is to land on the asteroid Ryugu to collect its surface materials. The key for a successful touchdown is to find a promising landing site that meets both scientific and engineering requirements. Due to the limited availability of pre-arrival information about Ryugu, the landing site selection (LSS) must be conducted based on proximity observations over a limited length of time. In addition, Ryugu was discovered to possess an unexpectedly high abundance of boulders with an absence of wide and flat areas, further complicating the LSS. To resolve these problems, we developed a systematic and stepwise LSS process with a focus on the surface topography of Ryugu and the associated touchdown safety. The proposed LSS scheme consists of two phases: Phase-I LSS, a comprehensive survey of potential landing areas at the 100-m scale based on the global mapping of Ryugu, and Phase-II LSS, a narrowing-down process of the candidate landing sites at the 10-m scale using high-resolution images and a local terrain model. To verify the feasibility of a precision landing at the target site, we also investigated the landing dispersion via a Monte Carlo simulation, which incorporates the effect of the irregular surface gravity field. One of the major characteristics of the Hayabusa2 LSS developed in this study is the iterative feedback between LSS analyses on the ground and actual spacecraft operations near the target asteroid. Using the newly developed method, we chose a landing site with a radius of 3 m, and Hayabusa2 successfully conducted its first touchdown on February 21, 2019. This paper reports the methodology and results of the stepwise iterative LSS for the first Hayabusa2 touchdown. The touchdown operation results reconstructed from flight data are also provided, demonstrating the validity of the adopted LSS strategy.

Purpose Preoperative opioid treatment increases postoperative adverse events. This study was aimed to analyze preoperative opioid prevalence in countries with low opioid consumption. Additionally, the effect of low opioid usage on postoperative outcomes was also investigated. Methods We conducted this single center retrospective cohort analysis in a Japanese university-affiliated hospital to investigate opioid usage and its impact on the duration of postoperative hospitalization and in-hospital mortality. Adult patients who underwent general anesthesia between 2015 and 2020 were included. We extracted the patients’ characteristics, surgical information and postoperative outcomes. Subgroup analysis to address opioid dose effect was performed in high and low dose opioid subgroups. Results Among 20,306 inpatients, 535 (2.63%) patients used opioids preoperatively. Tramadol was the most frequently used opioid. The median morphine equivalent (MME) dose was 15 mg/day. Median duration of hospitalization was 18 and 9 days in the opioid and non-opioid groups, and in-hospital mortality was 2.06% and 0.42%. Multivariable regression analysis demonstrated that preoperative opioid use was associated with a longer duration of hospitalization and in-hospital mortality. Subgroup analysis demonstrated longer durations of hospitalization in both high (> 30 mg/day MME) and low (≤ 30 mg/day MME) dose opioid groups, while higher in-hospital mortality was seen only in the high dose opioid group. Conclusions Preoperative opioid usage was one-tenth of the United States average. Despite its low prevalence and small dosage, preoperative opioid usage was associated with poor postoperative outcomes. Dedicated perioperative interventions to prevent opioid-associated adverse events should be developed even in countries with low opioid consumption.

The aim of this study was to evaluate the involvement of nanoparticles prepared from Allium cepa L. as anti-inflammatory agents. In the present study, we identified nanoparticles from Allium cepa L. using the ultracentrifugation exosome purification method. The nanoparticles were referred to as 17,000× g and 200,000× g precipitates, and they contained quercetins, proteins, lipids, and small-sized RNA. The nanoparticles inhibited nitric oxide production from lipopolysaccharide (LPS)-stimulated RAW264 cells without cytotoxic properties. Cellular incorporation was confirmed by laser microscopic observation after PKH26 staining. The inhibition of caveolae-dependent endocytosis and macropinocytosis significantly prevented the incorporation of the nanoparticles but had no effect on the inhibition of nitric oxide in RAW264 cells. Collectively, the identified nanoparticles were capable of inhibiting the LPS response via extracellular mechanisms. Taken together, the way of consuming Allium cepa L. without collapsing the nanoparticles is expected to provide an efficient anti-inflammatory effect.

Background Health literacy (HL) has gained increasing attention as a factor related to health behaviors and outcomes. This study aimed to investigate geographic differences in HL levels and effect modification by geographic area on their relationship with self-rated health in the Japanese population using a nationwide sample. Methods Data for this study were derived from a nationally representative cross-sectional survey on health information access for consumers in Japan using a mailed self-administered questionnaire in 2020 (INFORM Study 2020). Valid responses from 3,511 survey participants, selected using two-stage stratified random sampling, were analyzed in this study. HL was measured using the Communicative and Critical Health Literacy Scale (CCHL). Multiple regression and logistic regression analyses were conducted to examine the associations between geographic characteristics and HL and effect modification on the association between HL and self-rated health by geographic area, controlling for sociodemographic characteristics. Results The mean HL score was 3.45 (SD = 0.78), somewhat lower compared with previous studies on the Japanese general population. HL was higher in Kanto area than in Chubu area, after controlling for sociodemographic factors and municipality size. Furthermore, HL was positively associated with self-rated health after controlling for sociodemographic and geographic factors; however, this association was more evident in eastern areas than in western areas. Conclusion The findings indicate geographic differences in HL levels and effect modification by geographic area on the relationship between HL and self-rated health in the general Japanese population. HL was more strongly associated with self-rated health in eastern areas than in western areas. Further investigation is needed to explore the moderating effects of areal features, including the distribution of primary care physicians and social capital, when formulating strategies to improve HL in different contexts.

In-person models of genetic counseling (GC) have been the common method in Japan for pregnant women to receive GC. However, recent increases in the number of pregnant women considering undergoing prenatal testing have made it challenging to retain individualized in-person care. To explore pregnant women’s opinions toward pretest GC models and the ideal time duration, a self-administered questionnaire survey was conducted for women at their first prenatal visit. A total of 114 valid respondents (93.4%) were included in the analyses. Of these, 80.7% of women preferred in-person GC, followed by classroom (9.6%), group (3.5%), and telegenetic-based GC (2.6%). Women with experience in undergoing prenatal testing significantly did not prefer in-person GC ( p  = 0.05). Sixty-two women (54.4%) preferred a duration of 15–29 min for pretest GC sessions, followed by 30–59 min (28.9%) and <15 min (14.9%). Women’s preference of ≥30 min in length was significantly associated with anhedonia, singleton pregnancies, acquaintance with people with trisomy 21, and awareness of prenatal testing. Women who were unaware of the need for agreement with the partner for prenatal testing and who did not know the average life expectancy of a trisomy 21 patient significantly preferred <15 min in length over other durations. While the majority of women preferred in-person GC for <30 min, their preferences varied by their background characteristics, experiences, attitudes, and knowledge. These findings will help establish a prenatal GC system offering a choice of GC models in Japan; however, further large-scale studies are needed to confirm these findings.

Carbonaceous (C-type) asteroids 1 are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites 2 , 3 and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth’s atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR) 4 onboard the spacecraft Hayabusa2 5 , indicating that the asteroid’s boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m −2  s −0.5  K −1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites 6 and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect 7 , 8 . We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites 6 . These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity 9 of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies 10 . Thermal imaging data obtained from the spacecraft Hayabusa2 reveal that the carbonaceous asteroid 162173 Ryugu is an object of unusually high porosity.

In super-aged societies, dementia has become a critical issue, underscoring the urgent need for tools to assess cognitive status effectively in various sectors, including financial and business settings. Facial and speech features have been tried as cost-effective biomarkers of dementia including Alzheimer’s disease (AD). We aimed to establish an easy, automatic, and extensive screening tool for AD using a chatbot and artificial intelligence. Smile images and visual and auditory data of natural conversations with a chatbot from 99 healthy controls (HCs) and 93 individuals with AD or mild cognitive impairment due to AD (PwA) were analyzed using machine learning. A subset of 8 facial and 21 sound features successfully distinguished PwA from HCs, with a high area under the receiver operating characteristic curve of 0.94 ± 0.05. Another subset of 8 facial and 20 sound features predicted the cognitive test scores, with a mean absolute error as low as 5.78 ± 0.08. These results were superior to those obtained from face or auditory data alone or from conventional image depiction tasks. Thus, by combining spontaneous sound and facial data obtained through conversations with a chatbot, the proposed model can be put to practical use in real-life scenarios.