No abstract

No abstract

No abstract

Background:The cell type-specific induction of Bmp2 expression by Wnt3a indicates that Bmp2 is controlled by epigenetic mechanisms. Results: Epigenetic modification activates Bmp2 and Alp expression by Wnt3a in nonosteogenic cells. Conclusion: Epigenetic induction of Bmp2 production by Wnt3a reveals a new mechanistic dimension in morphogen-mediated control of osteogenesis. Significance: Epigenetic modifications/canonical Wnt3a signaling may provide a new method for trans-differentiation of nonosteogenic cells to osteoblasts.

Runx2 is the master transcription factor for bone formation. Haploinsufficiency of RUNX2 is the genetic cause of cleidocranial dysplasia (CCD) that is characterized by hypoplastic clavicles and open fontanels. In this study, we found that Pin1, peptidyl prolyl cis-trans isomerase, is a critical regulator of Runx2 in vivo and in vitro. Pin1 mutant mice developed CCD-like phenotypes with hypoplastic clavicles and open fontanels as found in the Runx2+/− mice. In addition Runx2 protein level was significantly reduced in Pin1 mutant mice. Moreover Pin1 directly interacts with the Runx2 protein in a phosphorylation-dependent manner and subsequently stabilizes Runx2 protein. In the absence of Pin1, Runx2 is rapidly degraded by the ubiquitin-dependent protein degradation pathway. However, Pin1 overexpression strongly attenuated uniquitin-dependent Runx2 degradation. Collectively conformational change of Runx2 by Pin1 is essential for its protein stability and possibly enhances the level of active Runx2 in vivo.

In this study, we propose a method for improving the stability of multilayer MoS field-effect transistors (FETs) by O plasma treatment and AlO passivation while sustaining the high performance of bulk MoS FET. The MoS FETs were exposed to O plasma for 30 s before AlO encapsulation to achieve a relatively small hysteresis and high electrical performance. A MoO layer formed during the plasma treatment was found between MoS and the top passivation layer. The MoO interlayer prevents the generation of excess electron carriers in the channel, owing to AlO passivation, thereby minimizing the shift in the threshold voltage (V) and increase of the off-current leakage. However, prolonged exposure of the MoS surface to O plasma (90 and 120 s) was found to introduce excess oxygen into the MoO interlayer, leading to more pronounced hysteresis and a high off-current. The stable MoS FETs were also subjected to gate-bias stress tests under different conditions. The MoS transistors exhibited negligible decline in performance under positive bias stress, positive bias illumination stress, and negative bias stress, but large negative shifts in V were observed under negative bias illumination stress, which is attributed to the presence of sulfur vacancies. This simple approach can be applied to other transition metal dichalcogenide materials to understand their FET properties and reliability, and the resulting high-performance hysteresis-free MoS transistors are expected to open up new opportunities for the development of sophisticated electronic applications.

In a previous study we found that nano-fibrous poly(L-lactic acid) scaffolds mimicking collagen fibers in size were superior to solid-walled scaffolds in promoting osteoblast differentiation and bone formation in vitro. In this study we used an in vivo model to confirm the biological properties of nano-fibrous poly(L-lactic acid) scaffolds and to evaluate how effectively they support bone regeneration against solid-walled scaffolds. The scaffolds were implanted in critical size defects made on rat calvarial bones. Compared with solid-walled scaffolds, nano-fibrous scaffolds supported substantially more new bone tissue formation, which was confirmed by micro-CT measurement and von Kossa staining. Goldner’s trichrome staining showed abundant collagen deposition in nano-fibrous scaffolds but not in the control solid-walled scaffolds. The cells in these scaffolds were immuno-stained strongly for Runx2 and bone sialoprotein (BSP). In contrast, solid-walled scaffolds implanted in the defects were stained weakly with trichrome, Runx2 and BSP. These in vivo results demonstrate that nano-fibrous architecture enhances osteoblast differentiation and bone formation.

Glioblastoma, the most common primary brain tumor in adults, is an incurable malignancy with poor short-term survival and is typically treated with radiotherapy along with temozolomide. While the development of tumor-treating fields (TTFields), electric fields with alternating low and intermediate intensity has facilitated glioblastoma treatment, clinical outcomes of TTFields are reportedly inconsistent. However, combinatorial administration of chemotherapy with TTFields has proven effective for glioblastoma patients. Sorafenib, an anti-proliferative and apoptogenic agent, is used as first-line treatment for glioblastoma. This study aimed to investigate the effect of sorafenib on TTFields-induced anti-tumor and anti-angiogenesis responses in glioblastoma cells in vitro and in vivo. Sorafenib sensitized glioblastoma cells to TTFields, as evident from significantly decreased post-TTFields cell viability (p < 0.05), and combinatorial treatment with sorafenib and TTFields accelerated apoptosis via reactive oxygen species (ROS) generation, as evident from Poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, use of sorafenib plus TTFields increased autophagy, as evident from LC3 upregulation and autophagic vacuole formation. Cell cycle markers accumulated, and cells underwent a G2/M arrest, with an increased G0/G1 cell ratio. In addition, the combinatorial treatment significantly inhibited tumor cell motility and invasiveness, and angiogenesis. Our results suggest that combination therapy with sorafenib and TTFields is slightly better than each individual therapy and could potentially be used to treat glioblastoma in clinic, which requires further studies.