Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy

Circadian rhythms, including sleep/wake cycles as well as hormonal, immune, metabolic, and cell proliferation rhythms, are fundamental biological processes driven by a cellular time-keeping system called the circadian clock. Disruptions in these rhythms due to genetic alterations or irregular lifestyles cause fundamental changes in physiology, from metabolism to cellular proliferation and differentiation, resulting in pathological consequences including cancer. Cancer cells are not uniform and static but exist as different subtypes with phenotypic and functional differences in the tumor microenvironment. At the top of the heterogeneous tumor cell hierarchy, cancer stem cells (CSCs), a self-renewing and multi-potent cancer cell type, are most responsible for tumor recurrence and metastasis, chemoresistance, and mortality. Phenotypically, CSCs are associated with the epithelial–mesenchymal transition (EMT), which confers cancer cells with increased motility and invasion ability that is characteristic of malignant and drug-resistant stem cells. Recently, emerging studies of different cancer types, such as glioblastoma, leukemia, prostate cancer, and breast cancer, suggest that the circadian clock plays an important role in the maintenance of CSC/EMT characteristics. In this review, we describe recent discoveries regarding how tumor intrinsic and extrinsic circadian clock-regulating factors affect CSC evolution, highlighting the possibility of developing novel chronotherapeutic strategies that could be used against CSCs to fight cancer.     

六方-BN对非晶前驱体制备不含添加剂的Si3N4/SiC复合材料相变的影响（英文）

Si3N4/SiC纳米复合材料由于具有优良的力学和热性能,广泛应用于涡轮发动机、热交换器和其他复杂情况中。然而,不添加添加剂很难制备出Si3N4/SiC复合材料。添加剂在烧结过程形成液相从而促进复合材料的致密化。然而,添加剂的存在降低了复合材料的高温力学性能。通常在不添加添加剂的情况下,采用电场辅助烧结,利用聚合物前体路线制备Si3N4/SiC复合材料。本研究中,在无添加剂、温度1700°C、真空50MPa条件下,热压烧结2h,利用非晶前体路线成功制备了六方-BN致密化的Si3N4/SiC复合材料。聚合物前驱体和BN的作用减少了的SiC含量。并对相变、致密化、微观组织和力学性能进行了讨论。     

One component metal oxide sintering additive for β-SiC based on thermodynamic calculation and experimental observations

This paper examines a range of metal oxides, including those containing relatively safe elements under neutron irradiation, such as Cr, Fe, Ta, Ti, V and W, as well as widely used oxides, Al₂O₃, MgO and Y₂O₃, as a sintering additive for β-SiC theoretically and experimentally. After selecting the most probable SiC oxidation reaction at 1973–2123 K, the condition where the metal oxide additive does not decompose SiC was calculated based on the standard Gibbs formation free energies. Thermodynamic calculations revealed that Al₂O₃, MgO and Y₂O₃ could be an effective sintering additive without decomposing SiC under hot pressing conditions, which was demonstrated experimentally. On the other hand, no one component metal oxide that contains a safe element for nuclear reactor applications was found to be an effective sintering additive due to the formation of metal carbides and/or silicides. Overall, the simulation based on thermodynamic calculations was found to be quite useful for selecting effective metal oxide additives.     

One component metal sintering additive for β-SiC based on thermodynamic calculation and experimental observations

Various types of metals were examined as sintering additives for β-SiC by considering the standard Gibbs formation free energy and vapor pressure under hot pressing conditions (1973-2123 K), particularly for applications in nuclear reactors. Metallic elements having the low long-term activation under neutron irradiation condition, such as Cr, Fe, Ta, Ti, V and W, as well as widely used elements, Al, Mg and B, were considered. The conclusions drawn from thermodynamic considerations were compared with the experimental observations. Al and Mg were found to be effective sintering additives, whereas the others were not due to the formation of metal carbides or silicides from the decomposition of SiC under hot pressing conditions.     

Chemothermal pulverization: Crushing titanate crystals to obtain nanosized powders via high-temperature treatment

In this study, we investigated chemothermal pulverization (CTP) phenomena that are induced in titanate single crystals and ceramics by high-temperature treatment at approximately 1000℃ under reactive gas containing ammonia and oxygen and cause these materials to break down into nanosized powders. Structural characterization revealed that there were many nanosized voids formed in titanates during heat treatment for CTP, and subsequent analysis revealed that these voids were filled with nitrogen gas. These results indicated that CTP consisted of four steps: the in-diffusion of nitride ions from the surface to titanates, the deposition of nitrogen molecules (gas) inside the titanate crystals instead of nitride formation, the growth of voids by further nitrogen transport from the surface to voids, and, finally, the breakdown of the walls between voids to form nanopowders. Furthermore, we discussed the exact mechanism of CTP phenomena by examining the effect of doping into titanates on the progress of CTP and by conducting theoretical calculations for the simulation of nitrogen impurities in titanate lattices.     

Rare-earth nitrate additives for the sintering of silicon carbide

Fourteen rare earth elements in their nitrate form were evaluated as sintering additives for β-SiC. All rare earth nitrates transformed to oxides by a reaction with the surface-adsorbed thin SiO₂ during heat treatment, which enhanced the density of the SiC monolith without decomposing SiC. In particular, Sc, Yb, Tm, Er and Ho were quite effective sintering additives; a > 99% relative density was observed by the addition of 5 wt.% rare earth oxide, whereas the other rare earth additives (Lu, Dy, Tb, Gd, Eu, Sm, Nd, Ce and La) revealed 77–92% density. Moreover, a fine 156 nm-sized SiC grain could be acquired by Sc addition, whereas the other additives showed a SiC grain size of approximately 1 μm. The mean hardness and K_Ic of the dense SiC containing rare earth elements were 24–27 GPa and 3.3–5.0 MPa m^1/2, respectively.