During embryonic development, epithelial cell blocks called somites are periodically formed according to the segmentation clock, becoming the foundation for the segmental pattern of the vertebral ...column. The process of somitogenesis has recently been recapitulated with murine and human pluripotent stem cells. However, an in vitro model for human somitogenesis coupled with the segmentation clock and epithelialization is still missing. Here, we report the generation of human somitoids, organoids that periodically form pairs of epithelial somite-like structures. Somitoids display clear oscillations of the segmentation clock that coincide with the segmentation of the presomitic mesoderm. The resulting somites show anterior-posterior and apical-basal polarities. Matrigel is essential for epithelialization but dispensable for the differentiation into somite cells. The size of somites is rather constant, irrespective of the initial cell number. The amount of WNT signaling instructs the proportion of mesodermal lineages in somitoids. Somitoids provide a novel platform to study human somitogenesis.
Black-monoclinic oxygen defective HfO2-x film with about 5 μm in a thickness was successfully formed on the surface of a metal Hf plate by controlled heat treatment in air. The black-monoclinic ...oxygen defective HfO2-x film was transformed into white body by further oxidation at higher temperature. Tauc plots using diffuse reflection data showed that impurity levels were formed within the energy gap for the black-monoclinic HfO2-x thin films. Based on the XPS analyses, the oxygen vacancy brought about the impurity levels. No cracks and voids were observed for the black-monoclinic HfO2-x films consisting of the fine columnar grains with the dimension of diameters of about 50 nm and lengths ranging from a few hundred nm to 1 μm.
•Black-ZrO2 thin films were successfully fabricated by simple oxidation.•The black-ZrO2 thin films are composed of equiaxed and columnar grains.•The bandgap of the black-ZrO2 thin films was estimated ...to be 0.72 eV.
Black-ZrO2 thin films were successfully fabricated on the surface of a Zr metal plate by simple oxidation at a controlled temperature in air, under normal atmospheric pressure. The black-ZrO2 thin films were composed of two types of grains with monoclinic ZrO2 structures: 1) fine equiaxed grains with sizes of up to a few hundred nanometers from the surface to a depth of about 5 μm; 2) columnar grains, with long and short diameters of several microns and a few hundred nanometers, respectively, in the inner region above the equiaxed grains. The bandgap of the black-ZrO2 thin films was estimated to be 0.72 eV, based on the Tauc plot using diffuse reflections, which allowed for absorption in the ultraviolet and visible regions of the solar spectrum.
A 3-μm-thick film of Magnéli Ti4O7 was successfully fabricated on the surface of Ti metal foil by a stepwise oxidation process involving annealing at 973 K in air followed by heating to 1173 K under ...a low oxygen partial pressure. Transmission electron microscopy and high-angle annular dark-field scanning transmission electron microscopy showed that the Magnéli Ti4O7 phase consisted of a period of four layers of equiaxial grains several hundreds of nanometers in size. The black Magnéli Ti4O7 thin film formed by our process absorbed light in the visible and near-infrared regions.
Figure (a) Appearance and (b) corresponding XRD patterns of a sample before and after heating. (I) Ti metal foil before heating, and after heating to (II) 973 K 10.8 ks in air, (III) 1173 K with no resting time in air, and two-step heat treatment involving heating at 973 K 10.8 ks in air and subsequent heating to 1173 K with no resting time under (IV) PO2 = 1.0 × 10−5 atm, (V) PO2 = 1.0 × 10−10 atm, respectively. Display omitted
Although azacitidine is the first‐line drug for higher‐risk myelodysplastic syndrome (MDS) patients, its efficacy for lower‐risk MDS remains unestablished. Therefore, we conducted a prospective study ...to examine the efficacy and safety of a 5‐day regimen of azacitidine (AZA‐5) for lower‐risk MDS. The primary endpoint was hematological improvement (HI) after 4 courses of therapy. A total of 51 patients with lower‐risk MDS based on the French‐American‐British (FAB) classification (44 patients with refractory anemia RA and 7 patients with refractory anemia with ringed sideroblasts RARS) were enrolled from 6 centers in Japan. The median age was 75 years (range: 51‐88). These patients received AZA‐5 (75 mg/m2; once daily for 5 sequential days). The median number of AZA‐5 courses was 8 (range: 1‐57), and 45 patients (88.2%) received more than 4 courses. HI and transfusion independency were seen in 24 patients (47.1%) and 11 patients (39.2%), respectively. A total of 11 patients (21.6%) achieved complete remission or marrow remission. WT1 mRNA levels were not significantly correlated with therapy response. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 26 (51.0%) and 11 (21.5%) patients, respectively. Nonhematological grade 3 or 4 adverse events were observed in 9 patients (17.6%). Together, these results indicate that AZA‐5 is feasible and effective for lower‐risk MDS patients as well as for higher‐risk MDS patients.
Five‐day regimen of azacitidine for lower‐risk MDS.
It remains unclear how changes in gene expression profiles that establish a pluripotent state are induced during cell reprogramming. Here we identify two forkhead box transcription factors, Foxd1 and ...Foxo1, as mediators of gene expression programme changes during reprogramming. Knockdown of Foxd1 or Foxo1 reduces the number of iPSCs, and the double knockdown further reduces it. Knockout of Foxd1 inhibits downstream transcriptional events, including the expression of Dax1, a component of the autoregulatory network for maintaining pluripotency. Interestingly, the expression level of Foxd1 is transiently increased in a small population of cells in the middle stage of reprogramming. The transient Foxd1 upregulation in this stage is correlated with a future cell fate as iPSCs. Fate mapping analyses further reveal that >95% of iPSC colonies are derived from the Foxd1-positive cells. Thus, Foxd1 is a mediator and indicator of successful progression of reprogramming.
The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care ...regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T). However, this trial was prematurely terminated because of poor recruitment. Using all data, there was no significant difference in the OS of patients between AZA-7 (92 patients) and AZA-5 (95 patients), with the 2-year OS rates of AZA-7 and AZA-5 at 36.4% and 25.8%, respectively (
P
= 0.293). Adverse event profiles were similar between the two groups. Interestingly, data of the centrally diagnosed RAEB and RAEB-T cases showed that AZA-7 significantly prolonged the time to leukemia transformation compared with AZA-5 (
P
= 0.022), confirmed by multivariate analysis. Although this trial could not provide definite evidence, the results support the use of AZA-7 for RAEB and RAEB-T. (UMIN Clinical Trials Registry UMIN000009633).
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