Pebbles and sand on asteroid (162173) Ryugu: In situ observation and particles returned to Earth.

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.

Hayabusa2 arrives at the carbonaceous asteroid 162173 Ryugu-A spinning top-shaped rubble pile.

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

Non-destructive elemental analysis of a carbonaceous chondrite with direct current Muon beam at MuSIC.

Electron- or X-ray-induced characteristic X-ray analysis has been widely used to determine chemical compositions of materials in vast research fields. In recent years, analysis of characteristic X-rays from muonic atoms, in which a muon is captured, has attracted attention because both a muon beam and a muon-induced characteristic X-ray have high transmission abilities. Here we report the first non-destructive elemental analysis of a carbonaceous chondrite using one of the world-leading intense direct current muon beam source (MuSIC; MUon Science Innovative Channel). We successfully detected characteristic muonic X-rays of Mg, Si, Fe, O, S and C from Jbilet Winselwan CM chondrite, of which carbon content is about 2 wt%, and the obtained elemental abundance pattern was consistent with that of CM chondrites. Because of its high sensitivity to carbon, non-destructive elemental analysis with a muon beam can be a novel powerful tool to characterize future retuned samples from carbonaceous asteroids.

Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer.

We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano-milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP-100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine.

Safety and efficacy of edoxaban, an oral factor xa inhibitor, for thromboprophylaxis after total hip arthroplasty in Japan and Taiwan.

Edoxaban, an oral direct factor Xa inhibitor, has proven antithrombotic efficacy. In a multicenter, phase II study, 264 total hip arthroplasty (THA) patients randomly received edoxaban 15 or 30 mg once daily or enoxaparin 2000IU (20-mg) twice daily for 11-14 days. Thromboembolic event incidences were 3.8% (3/78), 2.8% (2/72), and 4.1% (3/74) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively (P=1.00). Edoxaban-induced prolongation of prothrombin time, international normalized ratio, and activated partial thromboplastin time were proportional to plasma edoxaban concentration. Major or clinically relevant non-major bleeding incidences were 2.2% (2/89), 1.2% (1/85), and 2.3% (2/87) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively (P=1.00). Once-daily edoxaban showed similar efficacy and safety to enoxaparin for prevention of thromboembolic events in patients undergoing THA.

A new X-ray fluorescence spectroscopy for extraterrestrial materials using a muon beam.

The recent development of the intense pulsed muon source at J-PARC MUSE, Japan Proton Accelerator Research Complex/MUon Science Establishment (10(6) s(-1) for a momentum of 60 MeV/c), enabled us to pioneer a new frontier in analytical sciences. Here, we report a non-destructive elemental analysis using µ(-) capture. Controlling muon momentum from 32.5 to 57.5 MeV/c, we successfully demonstrate a depth-profile analysis of light elements (B, C, N, and O) from several mm-thick layered materials and non-destructive bulk analyses of meteorites containing organic materials. Muon beam analysis, enabling a bulk analysis of light to heavy elements without severe radioactivation, is a unique analytical method complementary to other non-destructive analyses. Furthermore, this technology can be used as a powerful tool to identify the content and distribution of organic components in future asteroidal return samples.

Screening of endophytic fungi having ability for antioxidative and alpha-glucosidase inhibitor activities isolated from Taxus sumatrana.

Endophytic microbes are considered as an important source of natural products. They show antibiotic, anticancer, antioxidative and antidiabetic activities. Therefore, there are many reports on the isolation and bioactivity screening of endophytic fungi from various plants including Taxus species. Taxus sumatrana (Miq.) de Laub is found in Indonesia. The objective of this study is to conduct an in vitro screening of 14 endophytic fungi isolated from Taxus sumatrana having antioxidative and alpha-glucosidase inhibitor activities. Each endophytic fungus was cultured for 7 days and the fungal mycelium and medium were extracted with methanol and ethyl acetate, respectively, to produce each extract. The antioxidative activity of each extract was tested by DPPH free radical scavenging activity and beta-carotene bleaching assays, whereas antidiabetic activity was tested based on alpha-glucosidase inhibitor activity. The screening results showed that fungal mycelia of TSC 13 had the best alpha-glucosidase inhibitor activity and TSC 24 had the best antioxidative activity. Isolation of bioactive compounds from TSC 13 and TSC 24 is being conducted. This is the first report that endophytic fungi isolated from T. sumatrana exhibited anti alpha-glucosidase inhibitory and anti oxidative activities.

Decomposition of lignin and holocellulose on Acacia mangium leaves and twigs by six fungal isolates from nature.

This research was conducted in the aim of preventing wild fire through reducing potential energy source to become in situ fertilizer. To prevent forest fires by reducing wood waste using lignocellulose-degrading fungi, six fungal isolates were tested for lignin and cellulose-degrading activity with Acacia mangium leaves and twigs over a period of 1 to 3 months. The fungi degraded 8.9-27.1% of the lignin and 14-31% of the holocellulose. The degradation rate varied depending on the fungal species. An increase in incubation time tended to decrease the amounts of holocellulose and lignin. However, the hot water soluble tended to increase following a longer incubation period. From the results obtained here, more time was needed to degrade lignin rather than other components in the sample.

A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty.

BACKGROUND: Edoxaban (the free base of DU-176b) is an oral, direct factor (F)Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. OBJECTIVES: The aim of the present study was to evaluate the efficacy and safety of edoxaban for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA). PATIENTS/METHODS: This was a randomized, double-blind, placebo-controlled, multicenter study conducted in Japan. A total of 523 Japanese patients were assigned to receive edoxaban 5, 15, 30 or 60 mg once daily or placebo for 11-14 days. A placebo control was used as neither low-molecular-weight heparin (LMWH) nor fondaparinux had been approved for thromboprophylaxis at the time of the study in Japan. The primary efficacy outcome was the incidence of VTE (lower-extremity deep vein thrombosis, symptomatic pulmonary embolism or symptomatic deep vein thrombosis). The primary safety outcome was the incidence of major and clinically relevant non-major bleeding. RESULTS: Edoxaban produced a significant dose-related reduction in VTE: the incidence of VTE was 29.5%, 26.1%, 12.5% and 9.1% in the edoxaban 5-, 15-, 30- and 60-mg treatment groups vs. 48.3% in the placebo group. The incidence of major and clinically relevant non-major bleeding was similar across all groups without any significant differences among edoxaban doses or between edoxaban and placebo. CONCLUSIONS: Edoxaban demonstrated significant dose-dependent reductions in VTE in patients undergoing TKA with a bleeding incidence similar to placebo. [This trial is registered with JAPIC, JapicCTI-060283 (ja).].

Isolation of antifungal compounds from Gardenia jasminoides.

Gardenia jasminoides E. (Rubiaceae) methanol extracts showed the highest level of antifungal activity against Pleurotus ostreatus, a wood-rotting fungus, compared to five other methanol plants extracts; [Thuja orientalis L. (Cupressaceae), Datura innoxia (Solanaceae), Ligustrum japonicum T. (Oleaceae), Juniperus chinensis var. procumbens (Cupressaceae) and Mallotus japonica M. (Euphorbiaceae)] and selected for further analysis. Two antifungal compounds were isolated from n-butanol and ethyl acetate solubles in the methanol extracts of Gardenia jasminoides leaves and stems by bioassay-guided fractionation, using Pleurotus ostreatus. The antifungal compounds found for the first time in Gardenia jasminoides against Pleurotus ostreatus were identified as genipin and geniposide based on instrumental analyses. Both also had potent inhibitory effects on two plant pathogenic fungi; Fusarium oxysporum and Corynespora cassiicola.

Screening of fungi capable of degrading lignocellulose from plantation forests.

In an effort to prevent forest fires after the clear cutting of plantation forests, fungi capable of degrading lignocelluloses were isolated to make a fertilizer from the logging waste. Seventy five fungal species were isolated from fruiting bodies and mycelia in plantation forests of South and North Sumatera, Indonesia. Sixty three of the fungi were identified based on the appearance and morphological characteristics of their fruiting bodies and mycelia, as Pycnoporus sanguineus, Dacryopinax spathularia, Schizophyllum commune, Polyporus sp. and Trametes sp. Twenty fungi were categorized as white-rot fungi and 12 as brown-rot fungi. Moreover, isolates 371, 368, 265, 346, 345 and 338 were selected using indicators and tested for the ability to degrade lignin and holo-cellulose in mangium wood meal over 1 to 4 weeks. Results showed that the 6 fungi could degrade lignin and holo-cellulose in wood meal. An increase in incubation time tended to decrease the amounts of lignin and holo-cellulose. Isolate 371 was found to be best at degrading lignin and holo-cellulose in mangium wood meal.

D-serine regulation: a possible therapeutic approach for central nervous diseases and chronic pain.

D-Serine, an endogenous modulator of NMDA receptors has been shown to play a vital role in many neuropsychiatric functions such as learning, memory, nociception and implicated in pathological conditions like schizophrenia and Alzheimer's disease. We propose possible therapeutic approaches for some CNS diseases and chronic pain, targeting the D-serine levels by manipulating its uptake, biosynthesis and metabolism.

Nocistatin attenuated the nociceptin induced c-Fos expression in the mouse hippocampus.

Nocistatin and nociceptin/orphaninFQ (N/OFQ) are the two new peptides which may have roles in nociception, memory, anxiety, and other biological functions. Nocistatin acts as a functional antagonist to N/OFQ in several functions, but their neuro-anatomical sites of interaction are unknown. We investigated the effect of combined intracerebroventricular (i.c.v.) injection of nocistatin with N/OFQ, on N/OFQ induced c-Fos expression in the mouse hippocampus, using c-Fos immunohistochemistry. We found that co-injection of nocistatin with N/OFQ significantly attenuated N/OFQ induced c-Fos expression in the hippocampus.

Temporal dynamics of dairy health and production in rural smallholder communities in Northern Vietnam.

The objective of this field study was to describe the temporal pattern of dairy cattle health and production and associated risk factors in rural small-holder communities in northern Vietnam, one of the target areas of the government's dairy development programme. A total of 99 dairy farms (11 per commune) were recruited from 9 of 32 communes in Ba Vi District, Ha Tay Province, using random two-stage cluster sampling. All dairy cattle present on the selected farms were included. After the initial questionnaire survey was conducted, farms were visited to collect follow-up information at 3-monthly intervals over a period of one year. The results suggest that offtake as well as mortality are important productivity indices because farmers sell or slaughter dairy cattle that are in poor health at low prices during summer months. Changes in relation to the farming operation suggest that for the farmers adopting dairy production it has become one of the main agricultural activities.

Combination chemotherapy with docetaxel and nedaplatin for recurrent esophageal cancer in an outpatient setting.

The purpose of this study was to address the feasibility of combination chemotherapy of docetaxel and nedaplatin for recurrent esophageal cancer patients in an outpatient setting. Patients received docetaxel (30 mg/m(2) intravenously) on day 1 and nedaplatin (40 mg/m(2) intravenously) on day 1 every 2 weeks. In total, 28 patients with recurrent esophageal cancer after the initial treatment (esophagectomy, chemotherapy and/or chemoradiotherapy) were enrolled. Each patient received six cycles of treatment and was evaluated with a computed tomography scan. The percentage of patients who completed this therapy was 60.7%. Complete response and partial response were achieved by 3.6% and 35.7% of patients, respectively. The most frequent toxicities were leukopenia and anemia; non-hematological toxicities were generally mild. There was no treatment-related death. The median survival time and 1-year survival rate were 8.5 months and 15.9%, respectively. This outpatient combination chemotherapy was useful as second-line chemotherapy for recurrent esophageal cancer.

Lhermitte sign during yawning associated with congenital partial aplasia of the posterior arch of the atlas.

We describe the case of a 26-year-old man who presented with symptoms compatible with Lhermitte sign that occurred during yawning. It was associated with congenital partial aplasia of the posterior arch of the atlas. Cervical multisection-detector CT myelography during yawning showed compression of the upper cervical cord due to the inward mobility of the isolated posterior tubercle. The symptoms completely disappeared following removal of the isolated posterior tubercle.

Metabolism of the calmodulin antagonist DY-9760e in animals and humans.

The in vitro metabolism of the calmodulin antagonist DY-9760e was investigated using liver microsomes from humans and three other animal species and compared with the in vivo metabolism in rats after intravenous administration of DY-9760e. Seven major metabolites were produced by human liver microsomes by the following metabolic pathways: N-dealkylation, phenyl hydroxylation, O-demethylation and imidazole oxidation. These metabolites were also produced by liver microsomes from monkeys, dogs and rats; additionally, a hydroxylated derivative of the indazole moiety was produced only by rat microsomes. To identify the structures of two imidazole ring metabolites whose authentic compounds could not be obtained, Escherichia coli co-expressing human cytochrome P450 CYP3A4 and NADPH-P450 reductase was used to biosynthesize these metabolites. NMR spectra elucidated the precise structures; oxidation occurred at the imidazole ring, and the subsequent ring-opening resulted in the generation of amide and formylamine groups. Glucuronide conjugates of the hydroxylated and O-demethylated derivatives were major components in rat bile. Therefore, DY-9760e metabolites generated in vitro correspond to the aglycones of the major metabolites observed in rat bile.

Ganglion-associated ulnar tunnel syndrome treated by ultrasonographically assisted aspiration and splinting.

We describe a case of ulnar nerve compression at the wrist due to a ganglion. This was treated by aspiration of the ganglion under ultrasonography and splinting because the patient was pregnant. The ulnar nerve palsy resolved completely and the ganglion disappeared. A follow-up ultrasonographic examination after 2 years showed no recurrence of the ganglion.

Clinical significance of CD151 gene expression in non-small cell lung cancer.

Transmembrane 4 superfamily (TM4SF) is a recently described gene family, and TM4SF members are known to play roles in the signal transduction pathways and to regulate cell activation, development, proliferation, and motility. MRP-1/CD9, KAI1/CD82, and ME491/CD63, members of the TM4SF, have been reported to suppress tumor progression or metastasis. Previously, we showed that MRP-1/CD9 suppressed cell motility and metastatic potential to lungs. Moreover, reduction of MRP-1/CD9 and KAI1/CD82 gene expression was found to be a factor in a poor prognosis for patients with non-small cell lung cancer. However, among TM4SF, CD151 is identical to an existing gene, PETA-3, which may promote tumor metastasis of malignant cells, and its expression may be involved in the malignant progression of cancer. The function of CD151 is opposite that of the metastasis suppressor genes, MRP-1/CD9 and KAI1/CD82. On the basis of these results, we used reverse transcription-PCR and immunohistochemical techniques for a retrospective study of CD151 gene expression in tumor tissues from 145 lung cancer patients; 72 tumors were stage I, 29 stage II, 27 stage IIIA, and 17 stage IIIB. Whereas 86 patients had tumors positive for the CD151 gene, 59 had tumors that were negative for the CD151 gene. The overall survival rate of patients with CD151-positive tumors was much lower than that of CD151-negative patients (51.9% versus 73.1%; P = 0.013). Our findings suggest that high CD151 gene expression in lung cancer may be associated with a poor prognosis. Assessment of CD151 could be instrumental for improvements in lung cancer diagnosis and therapies.

Usefulness of tc-99m MIBI SPECT in predicting multidrug resistance gene expression levels in non-small cell lung cancer--a preliminary report.

In this study we investigated whether Tc-99m hexakis 2-methoxy isobutyl isonitnile (Tc-99m MIBI) single-photon emission computed tomography (SPECT) has a correlation with the multidrug resistance (MDRI) and multidrug resistance-associated protein (MRP1) gene expression levels in non-small cell lung cancer (NSCLC). Fifteen patients with NSCLC were studied. SPECT images were obtained 15 (early) and 120 (delayed) min after injection of Tc-99m MIBI. We chose only one transverse section and set the region of interest over the tumor and out of the body. The mean counts in the tumor on early and delayed images were corrected by using those in the background and represented as Te and Td, respectively. Resected tumor specimens were frozen with liquid nitrogen and each positive control cell line was cultured. After the total ribonucleic acid (RNA) was extracted from specimens and cell lines, the complimentary deoxyribonucleic acid (cDNA) was amplified by the reverse transcription-polymerase chain reaction (RT-PCR) method. Each product was electrophoresed and fluorointensity was measured. The gene expression level was represented as the ratio of that of the positive control cell line. Te and Td indicated a significant correlation with the MDR1 gene expression level (p = 0.015 and p = 0.022), but not the gene of MRP1 (p = 0.100 and p = 0.145). In conclusion, Te and Td are useful parameters in predicting the MDRI gene expression level, but not MRPI in NSCLC.