Bile Duct Regeneration with an Artificial Bile Duct Made of Gelatin Hydrogel Nonwoven Fabrics

Although choledochojejunostomy is the standard technique for biliary reconstruction, there are various associated problems that need to be solved such as reflux cholangitis. Interposition with an artificial bile duct (ABD) to replace the resected bile duct maintains a physiological conduit for bile and may solve this problem. This study investigated the usefulness of an ABD made of gelatin hydrogel nonwoven fabric (GHNF). GHNF was prepared by the solution blow spinning method. The migration and activity of murine fibroblast L929 cells were examined in GHNF sheets. L929 cells migrated into GHNF sheets, where they proliferated and synthesized collagen, suggesting GHNF is a promising scaffold for bile duct regeneration. ABDs made of GHNF were implanted in place of resected bile duct segments in rats. The rats were killed at 2, 6, and 12 weeks postimplantation. The implantation site was histologically evaluated for bile duct regeneration. At postoperative 2 weeks, migrating cells were observed in the ABD pores. The implanted ABD was mostly degraded and replaced by collagen fibers at 6 weeks. Ki67-positive bile duct epithelial cells appeared within the implanted ABD. These were most abundant within the central part of the ABD after 6 weeks. The percentages of Ki67-positive cells were 31.7 ± 9.1% in the experimental group and 0.8 ± 0.6% in the sham operation group at 6 weeks (p < 0.05), indicating that mature biliary epithelial cells at the stump proliferated to regenerate the biliary epithelium. Biliary epithelial cells had almost completely covered the bile duct lumen at 12 weeks (epithelialization ratios: 10.4 ± 6.9% at 2 weeks, 93.1 ± 5.1% at 6 weeks, 99.2 ± 1.6% at 12 weeks). The regenerated epithelium was positive for the bile duct epithelium marker cytokeratin 19. Bile duct regeneration was accompanied by angiogenesis, as evidenced by the appearance of CD31-positive vascular structures. Capillaries were induced 2 weeks after implantation. The number of capillaries reached a maximum at 6 weeks and decreased to the same level as that of normal bile ducts at 12 weeks. These results showed that an ABD of GHNF contributed to successful bile duct regeneration in rats by facilitating the cell migration required for extracellular matrix synthesis, angiogenesis, and epithelialization. Impact Statement Development of an artificial bile duct (ABD) enables physiological biliary reconstruction and may solve clinical problems associated with choledochojejunostomy. In this study, we created ABDs with gelatin hydrogel nonwoven fabric and implanted them in place of resected bile duct in rats. We evaluated the process of bile duct regeneration as well as decomposition of the ABD and demonstrated successful regeneration of resected bile duct, highlighting the possibility of this novel biliary reconstruction method to replace choledochojejunostomy

The Shock State of Itokawa Sample

One of the fundamental aspects of any astromaterial is its shock history, since this factor elucidates critical historical events, and also because shock metamorphism can alter primary mineralogical and petrographic features, and reset chronologies [1]. Failure to take shock history into proper account during characterization can result in seriously incorrect conclusions being drawn. Thus the Hayabusa Preliminary Examination Team (HASPET) made shock stage determination of the Itokawa samples a primary goal [2]. However, we faced several difficulties in this particular research. The shock state of ordinary chondrite materials is generally determined by simple optical petrographic observation of standard thin sections. The Itokawa samples available to the analysis team were mounted into plastic blocks, were polished on only one side, and were of non-standard and greatly varying thickness, all of which significantly complicated petrographic analysis but did not prevent it. We made an additional estimation of the sample shock state by a new technique for this analysis - electron back-scattered diffraction (EBSD) in addition to standard petrographic techniques. We are also investigating the crystallinity of Itokawa olivine by Synchrotron X-ray diffraction (SXRD)

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

Background The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. Methods and results We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). Conclusions The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population

A history of mild shocks experienced by the regolith particles on hydrated asteroid Ryugu

Micrometeorites, a possible major source of Earth’s water, are thought to form from explosive dispersal of hydrated chondritic materials during impact events on their parental asteroids. However, this provenance and formation mechanism have yet to be directly confirmed using asteroid returned samples. Here, we report evidence of mild shock metamorphism in the surface particles of asteroid Ryugu based on electron microscopy. All particles are dominated by phyllosilicates but lack dehydration textures, which are indicative of shock-heating temperatures below ~500 °C. Microfault-like textures associated with extensively shock-deformed framboidal magnetites and a high-pressure polymorph of Fe–Cr–sulfide have been identified. These findings indicate that the average peak pressure was -2 GPa. The vast majority of ejecta formed during impact on Ryugu-like asteroids would be hydrated materials, larger than a millimetre, originating far from the impact point. These characteristics are inconsistent with current micrometeorite production models, and consequently, a new formation mechanism is required

Oxygen isotope evidence from Ryugu samples for early water delivery to Earth by CI chondrites

The delivery of water to the inner Solar System, including Earth, is still a debated topic. A preferential role for hydrated asteroids in this process is supported by isotopic measurements. Carbonaceous chondrite (CC) meteorites represent our main source of information about these volatile-rich asteroids. However, the destruction of weaker materials during atmospheric entry creates a bias in our CC data. The return of surface materials from the C-type asteroid 162173 Ryugu by the Hayabusa2 spacecraft provides a unique opportunity to study high-porosity, low-density, primitive materials, unrepresented in the meteorite record. We measured the bulk oxygen isotope composition from four Ryugu particles and show that they most closely resemble the rare CI (CC Ivuna-type) chondrites, but with some differences that we attribute to the terrestrial contamination of the CI meteorites. We suggest that CI-related material is widespread among carbonaceous asteroids and a more important source of Earth’s water and other volatiles than its limited presence in our meteoritic collection indicates

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition