Chronic ingestion of soy peptide supplementation reduces aggressive behavior and abnormal fear memory caused by juvenile social isolation.

Juvenile loneliness is a risk factor for psychopathology in later life. Deprivation of early social experience due to peer rejection has a detrimental impact on emotional and cognitive brain function in adulthood. Accumulating evidence indicates that soy peptides have many positive effects on higher brain function in rodents and humans. However, the effects of soy peptide use on juvenile social isolation are unknown. Here, we demonstrated that soy peptides reduced the deterioration of behavioral and cellular functions resulting from juvenile socially-isolated rearing. We found that prolonged social isolation post-weaning in male C57BL/6J mice resulted in higher aggression and impulsivity and fear memory deficits at 7 weeks of age, and that these behavioral abnormalities, except impulsivity, were mitigated by ingestion of soy peptides. Furthermore, we found that daily intake of soy peptides caused upregulation of postsynaptic density 95 in the medial prefrontal cortex and phosphorylation of the cyclic adenosine monophosphate response element binding protein in the hippocampus of socially isolated mice, increased phosphorylation of the adenosine monophosphate-activated protein kinase in the hippocampus, and altered the microbiota composition. These results suggest that soy peptides have protective effects against juvenile social isolation-induced behavioral deficits via synaptic maturation and cellular functionalization.

Nonmagnetic framboid and associated iron nanoparticles with a space-weathered feature from asteroid Ryugu.

Extraterrestrial minerals on the surface of airless Solar System bodies undergo gradual alteration processes known as space weathering over long periods of time. The signatures of space weathering help us understand the phenomena occurring in the Solar System. However, meteorites rarely retain the signatures, making it impossible to study the space weathering processes precisely. Here, we examine samples retrieved from the asteroid Ryugu by the Hayabusa2 spacecraft and discover the presence of nonmagnetic framboids through electron holography measurements that can visualize magnetic flux. Magnetite particles, which normally provide a record of the nebular magnetic field, have lost their magnetic properties by reduction via a high-velocity (>5 km s-1) impact of a micrometeoroid with a diameter ranging from 2 to 20 µm after destruction of the parent body of Ryugu. Around these particles, thousands of metallic-iron nanoparticles with a vortex magnetic domain structure, which could have recorded a magnetic field in the impact event, are found. Through measuring the remanent magnetization of the iron nanoparticles, future studies are expected to elucidate the nature of the nebular/interplanetary magnetic fields after the termination of aqueous alteration in an asteroid.

Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019.

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.

Microstructural and chemical features of impact melts on Ryugu particle surfaces: Records of interplanetary dust hit on asteroid Ryugu.

The Hayabusa2 spacecraft delivered samples of the carbonaceous asteroid Ryugu to Earth. Some of the sample particles show evidence of micrometeoroid impacts, which occurred on the asteroid surface. Among those, particles A0067 and A0094 have flat surfaces on which a large number of microcraters and impact melt splashes are observed. Two impact melt splashes and one microcrater were analyzed to unveil the nature of the objects that impacted the asteroid surface. The melt splashes consist mainly of Mg-Fe-rich glassy silicates and Fe-Ni sulfides. The microcrater trapped an impact melt consisting mainly of Mg-Fe-rich glassy silicate, Fe-Ni sulfides, and minor silica-rich glass. These impact melts show a single compositional trend indicating mixing of Ryugu surface materials and impactors having chondritic chemical compositions. The relict impactor in one of the melt splashes shows mineralogical similarity with anhydrous chondritic interplanetary dust particles having a probable cometary origin. The chondritic micrometeoroids probably impacted the Ryugu surface during its residence in a near-Earth orbit.

Reassigning CI chondrite parent bodies based on reflectance spectroscopy of samples from carbonaceous asteroid Ryugu and meteorites.

The carbonaceous asteroid Ryugu has been explored by the Hayabusa2 spacecraft to elucidate the actual nature of hydrous asteroids. Laboratory analyses revealed that the samples from Ryugu are comparable to unheated CI carbonaceous chondrites; however, reflectance spectra of Ryugu samples and CIs do not coincide. Here, we demonstrate that Ryugu sample spectra are reproduced by heating Orgueil CI chondrite at 300°C under reducing conditions, which caused dehydration of terrestrial weathering products and reduction of iron in phyllosilicates. Terrestrial weathering of CIs accounts for the spectral differences between Ryugu sample and CIs, which is more severe than space weathering that likely explains those between asteroid Ryugu and the collected samples. Previous assignments of CI chondrite parent bodies, i.e., chemically most primitive objects in the solar system, are based on the spectra of CI chondrites. This study indicates that actual spectra of CI parent bodies are much darker and flatter at ultraviolet to visible wavelengths than the spectra of CI chondrites.

Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium.

Polycyclic aromatic hydrocarbons (PAHs) contain ≲20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures ≳1000 kelvin), by reactions within cold (~10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-13C substituted compositions (Δ2×13C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51‰ higher than values expected for a stochastic distribution of isotopes. The Δ2×13C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Δ2×13C values consistent with formation by higher-temperature reactions.

Soluble organic matter Molecular atlas of Ryugu reveals cold hydrothermalism on C-type asteroid parent body.

The sample from the near-Earth carbonaceous asteroid (162173) Ryugu is analyzed in the context of carbonaceous meteorites soluble organic matter. The analysis of soluble molecules of samples collected by the Hayabusa2 spacecraft shines light on an extremely high molecular diversity on the C-type asteroid. Sequential solvent extracts of increasing polarity of Ryugu samples are analyzed using mass spectrometry with complementary ionization methods and structural information confirmed by nuclear magnetic resonance spectroscopy. Here we show a continuum in the molecular size and polarity, and no organomagnesium molecules are detected, reflecting a low temperature and water-rich environment on the parent body approving earlier mineralogical and chemical data. High abundance of sulfidic and nitrogen rich compounds as well as high abundance of ammonium ions confirm the water processing. Polycyclic aromatic hydrocarbons are also detected in a structural continuum of carbon saturations and oxidations, implying multiple origins of the observed organic complexity, thus involving generic processes such as earlier carbonization and serpentinization with successive low temperature aqueous alteration.

A Case of Lamina Lucida-Type Linear IgA Disease Complicated by Colon Polyposis and Rectal Adenocarcinoma.

Linear IgA disease (LAD) is a rare autoimmune bullous disease characterized by IgA deposition in the basement membrane zone (BMZ). A 66-year-old male was treated for myelodysplastic syndrome at our hospital for 5 years, during which his condition remained stable. He visited our department because of erythema with itching, which appeared 1 year ago and gradually exacerbated with the development of blisters and erosions. During the first visit, multiple erythemas with erosions and crusts on their periphery were observed on the trunk and lower limbs. Histopathological examination revealed subepidermal blisters with inflammatory cell infiltration, mainly constituting of neutrophils, eosinophils, and lymphocytes. Direct and indirect immunofluorescence showed linear IgA deposits in the BMZ and IgA anti-BMZ antibodies, respectively, while immunoblotting using a concentrated culture supernatant of HaCaT cells detected IgA antibodies reactive to 120-kDa LAD-1. Accordingly, the patient was diagnosed with lamina lucida-type LAD. Subsequent colonoscopy revealed multiple colorectal polyps and rectal adenocarcinoma (Tis, N0, and M0). Multigene panel test showed an ATM variant of unknown significance but did not detect any pathogenic variants associated with intestinal polyposis syndrome. The skin lesions quickly resolved with oral diaphenylsulfone 50 mg/day and resection of the colorectal polyps and adenocarcinoma. To our knowledge, this is the first reported case of LAD associated with multiple colorectal polyps and rectal adenocarcinoma. Additionally, we also analyzed reported cases of LAD associated with malignancy from the literature.

Chemical evolution of primordial salts and organic sulfur molecules in the asteroid 162173 Ryugu.

Samples from the carbonaceous asteroid (162173) Ryugu provide information on the chemical evolution of organic molecules in the early solar system. Here we show the element partitioning of the major component ions by sequential extractions of salts, carbonates, and phyllosilicate-bearing fractions to reveal primordial brine composition of the primitive asteroid. Sodium is the dominant electrolyte of the salt fraction extract. Anions and NH4+ are more abundant in the salt fraction than in the carbonate and phyllosilicate fractions, with molar concentrations in the order SO42- > Cl- > S2O32- > NO3- > NH4+. The salt fraction extracts contain anionic soluble sulfur-bearing species such as Sn-polythionic acids (n < 6), Cn-alkylsulfonates, alkylthiosulfonates, hydroxyalkylsulfonates, and hydroxyalkylthiosulfonates (n < 7). The sulfur-bearing soluble compounds may have driven the molecular evolution of prebiotic organic material transforming simple organic molecules into hydrophilic, amphiphilic, and refractory S allotropes.

Visualization of nanoscale magnetic domain states in the asteroid Ryugu.

In the samples collected from the asteroid Ryugu, magnetite displays natural remanent magnetization due to nebular magnetic field, whereas contemporaneously grown iron sulfide does not display stable remanent magnetization. To clarify this counterintuitive feature, we observed their nanoscale magnetic domain structures using electron holography and found that framboidal magnetites have an external magnetic field of 300 A m-1, similar to the bulk value, and its magnetic stability was enhanced by interactions with neighboring magnetites, permitting a disk magnetic field to be recorded. Micrometer-sized pyrrhotite showed a multidomain magnetic structure that was unable to retain natural remanent magnetization over a long time due to short relaxation time of magnetic-domain-wall movement, whereas submicron-sized sulfides formed a nonmagnetic phase. These results show that both magnetite and sulfide could have formed simultaneously during the aqueous alteration in the parent body of the asteroid Ryugu.

Insights into the formation and evolution of extraterrestrial amino acids from the asteroid Ryugu.

All life on Earth contains amino acids and carbonaceous chondrite meteorites have been suggested as their source at the origin of life on Earth. While many meteoritic amino acids are considered indigenous, deciphering the extent of terrestrial contamination remains an issue. The Ryugu asteroid fragments (JAXA Hayabusa2 mission), represent the most uncontaminated primitive extraterrestrial material available. Here, the concentrations of amino acids from two particles from different touchdown sites (TD1 and TD2) are reported. The concentrations show that N,N-dimethylglycine (DMG) is the most abundant amino acid in the TD1 particle, but below detection limit in the other. The TD1 particle mineral components indicate it experienced more aqueous alteration. Furthermore, the relationships between the amino acids and the geochemistry suggest that DMG formed on the Ryugu progenitor body during aqueous alteration. The findings highlight the importance of aqueous chemistry for defining the ultimate concentrations of amino acids in primitive extraterrestrial samples.

Uracil in the carbonaceous asteroid (162173) Ryugu.

The pristine sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by the Hayabusa2 spacecraft enabled us to analyze the pristine extraterrestrial material without uncontrolled exposure to the Earth's atmosphere and biosphere. The initial analysis team for the soluble organic matter reported the detection of wide variety of organic molecules including racemic amino acids in the Ryugu samples. Here we report the detection of uracil, one of the four nucleobases in ribonucleic acid, in aqueous extracts from Ryugu samples. In addition, nicotinic acid (niacin, a B3 vitamer), its derivatives, and imidazoles were detected in search for nitrogen heterocyclic molecules. The observed difference in the concentration of uracil between A0106 and C0107 may be related to the possible differences in the degree of alteration induced by energetic particles such as ultraviolet photons and cosmic rays. The present study strongly suggests that such molecules of prebiotic interest commonly formed in carbonaceous asteroids including Ryugu and were delivered to the early Earth.

Chondrule-like objects and Ca-Al-rich inclusions in Ryugu may potentially be the oldest Solar System materials.

Chondrule-like objects and Ca-Al-rich inclusions (CAIs) are discovered in the retuned samples from asteroid Ryugu. Here we report results of oxygen isotope, mineralogical, and compositional analysis of the chondrule-like objects and CAIs. Three chondrule-like objects dominated by Mg-rich olivine are 16O-rich and -poor with Δ17O (=δ17O - 0.52 × Î´18O) values of ~ -23‰ and ~ -3‰, resembling what has been proposed as early generations of chondrules. The 16O-rich objects are likely to be melted amoeboid olivine aggregates that escaped from incorporation into 16O-poor chondrule precursor dust. Two CAIs composed of refractory minerals are 16O-rich with Δ17O of ~ -23‰ and possibly as old as the oldest CAIs. The discovered objects (<30 µm) are as small as those from comets, suggesting radial transport favoring smaller objects from the inner solar nebula to the formation location of the Ryugu original parent body, which is farther from the Sun and scarce in chondrules. The transported objects may have been mostly destroyed during aqueous alteration in the Ryugu parent body.

Basal cell carcinoma of the umbilicus associated with sweat gland structures: Two case reports.

RATIONALE: Basal cell carcinoma (BCC) arising in the umbilicus is relatively rare, and in particular, there have been few reports mentioning peritumoral sweat gland structures histopathologically. We herein, report 2 cases of umbilical BCC with sweat gland structures within and around the tumor. PATIENT CONCERNS: A 61-year-old woman had a 2-year history of black exudative plaque in her umbilicus, and an 80-year-old woman had a 6-month history of dark brownish plaque in the umbilicus, with exudation 2 months prior to her first visit. DIAGNOSES: Based on the histopathological finding, both cases were confirmed as BCC. The results of immunohistochemical staining showed that the tumor cells were Ber-EP4 positive. In addition, EMA-positive glandular structures were seen within and around the tumor. INTERVENTIONS: Curative resection at the level of the linea alba on the bottom side was performed. OUTCOMES: No relapse has been observed since resection in either patient. LESSONS: We herein report 2 cases of umbilical BCC with sweat glands and ducts. Although whether peri- and/or intra-tumor sweat gland structures are the source of the tumor or arise by transdifferentiation from tumor cells remains unclear, these findings may provide clues to help understand the morphopathogenesis of umbilical BCC in the future.

Soluble organic molecules in samples of the carbonaceous asteroid (162173) Ryugu.

The Hayabusa2 spacecraft collected samples from the surface of the carbonaceous near-Earth asteroid (162173) Ryugu and brought them to Earth. The samples were expected to contain organic molecules, which record processes that occurred in the early Solar System. We analyzed organic molecules extracted from the Ryugu surface samples. We identified a variety of molecules containing the atoms CHNOS, formed by methylation, hydration, hydroxylation, and sulfurization reactions. Amino acids, aliphatic amines, carboxylic acids, polycyclic aromatic hydrocarbons, and nitrogen-heterocyclic compounds were detected, which had properties consistent with an abiotic origin. These compounds likely arose from an aqueous reaction on Ryugu's parent body and are similar to the organics in Ivuna-type meteorites. These molecules can survive on the surfaces of asteroids and be transported throughout the Solar System.

Comparable efficacy of denosumab and romosozumab in patients with rheumatoid arthritis receiving glucocorticoid administration.

OBJECTIVES: Romosozumab is a newly released and widely known molecular-targeted drug for severe osteoporosis treatment with comparable effectiveness to denosumab. However, there have been no reports discussing the efficacy of those treatments for rheumatoid arthritis (RA) patients, especially those receiving glucocorticoids. This retrospective observational registry study compared the efficacy of 12-month treatment of denosumab and romosozumab in RA patients under the influence of glucocorticoid intake. METHODS: Following propensity score matching, 36 patients each in the denosumab and romosozumab groups were analysed in this study. Drug effectiveness was evaluated by measuring bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck at baseline, 6 and 12 months as well as alterations in P1NP, TRACP-5b, and simplified disease activity index (SDAI). The occurrence of adverse events and new fractures was also assessed. RESULTS: At 12 months of treatment, BMD at the lumbar spine was increased by 7.5% in the denosumab group and 8.7% in the romosozumab group, which were both significantly and comparably elevated over baseline. At the total hip and femoral neck, romosozumab tended to exhibit favourable efficacy to increase BMD versus denosumab. Both P1NP and TRACP-5b were significantly lower in the denosumab group as compared with the baseline. Conversely in the romosozumab group, P1NP was increased over baseline, while TRACP-5b was decreased. Regarding SDAI alterations, both the romosozumab and denosumab groups exhibited comparable improvements in RA disease activity over time during treatment. Recorded adverse events and new fractures during treatment were few and minor in both groups. CONCLUSIONS: Romosozumab exhibited comparable efficacy to denosumab for increasing BMD even under the influence of glucocorticoids for treating RA. Both drugs may be therefore suitable for managing osteoporosis in patients with RA and glucocorticoid intake.

Rare earth element identification and quantification in millimetre-sized Ryugu rock fragments from the Hayabusa2 space mission.

Millimetre-sized primordial rock fragments originating from asteroid Ryugu were investigated using high energy X-ray fluorescence spectroscopy, providing 2D and 3D elemental distribution and quantitative composition information on the microscopic level. Samples were collected in two phases from two sites on asteroid Ryugu and safely returned to Earth by JAXA's asteroid explorer Hayabusa2, during which time the collected material was stored and maintained free from terrestrial influences, including exposure to Earth's atmosphere. Several grains of interest were identified and further characterised to obtain quantitative information on the rare earth element (REE) content within said grains, following a reference-based and computed-tomography-assisted fundamental parameters quantification approach. Several orders of magnitude REE enrichments compared to the mean CI chondrite composition were found within grains that could be identified as apatite phase. Small enrichment of LREE was found for dolomite grains and slight enrichment or depletion for the general matrices within the Ryugu rock fragments A0055 and C0076, respectively. Supplementary Information: The online version contains supplementary material available at 10.1186/s40623-022-01705-3.

Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy: The prospective VICTOR study.

Romosozumab is a potent drug for treating postmenopausal osteoporosis but has a limited dosing period of 12 months. Bone mineral density (BMD) decreases soon after romosozumab discontinuation, thus emphasizing the importance of appropriate sequential treatment. The present VICTOR randomized controlled study compared the efficacy of ibandronate and denosumab as sequential therapy options following 12-month romosozumab treatment. Subjects completing 12 months of romosozumab administration for severe postmenopausal osteoporosis were randomly assigned to receive either ibandronate or denosumab for an additional 12 months. The primary outcome of interest was the percentage changes in BMD at the lumbar spine, total hip, and femoral neck from 12 months (completion of romosozumab) to 18 and 24 months of total treatment (6 and 12 months, respectively, after the conversion to sequential therapy). Secondary outcomes included alterations in serum bone turnover markers and the incidence of adverse events. Sixty-two subjects each in the ibandronate and denosumab groups completed the sequential therapy. The respective percentage changes in BMD at the lumbar spine from 12 months to 24 months were 2.5 % in the ibandronate group and 5.4 % in the denosumab group. At 24 months, we observed significant differences versus 12 months for both groups as well as between the groups (all P < 0.01), showing a superior ability to increase BMD at the lumbar spine for denosumab over ibandronate. BMD gains at the total hip and femoral neck exhibited comparably favorable trends. P1NP and TRACP-5b were significantly decreased from 12 to 24 months (-64.9 % and - 26.8 % in the ibandronate group and - 67.4 % and - 36.3 % in the denosumab group, respectively; all P < 0.001 versus 12 months). Several minor adverse events were recorded in both groups, none of which led to the discontinuation of the trial. The VICTOR study revealed that denosumab could be considered more effective than ibandronate, with few severe adverse events, for the enhancement of BMD as a sequential agent after romosozumab in postmenopausal osteoporosis patients.