Corneal endothelial dysfunction occurs when corneal endothelial cells (CECs) are dramatically lost and eventually results in vision loss. Corneal transplantation is the only solution at present. However, corneal transplantation requires a fresh human cornea and there is a worldwide shortage of donors. Therefore, finding new functional CECs to replace human CECs is urgent. Skin-derived precursors (SKPs) can be easily acquired and have multiple differential potential. We co-cultured human SKPs with B4G12 cells in serum-free medium and obtained abundant CEC-like cells which had similar morphology and characteristic to human CECs. CEC-like cells exerted excellent therapeutic effect when they were transplanted into rabbit and monkey corneal endothelial dysfunction models by injection method. This protocol enables efficient production of CEC-like cells from SKPs. The renewable cell source, novel derivation method and simple treatment strategy may lead to potential applications in cell replacement therapy for corneal endothelial dysfunction.Corneal endothelial cells (CECs) are a monolayer of hexagonal cells covering the posterior surface of the cornea, and serve as a barrier between the corneal stroma and the aqueous humor. The tight junction as well as the ionic "pump" functions of CECs are important factors that maintain corneal transparency 1 . Many pathological factors such as trauma, surgery, and inflammation may cause dramatic loss of endothelial cell density, resulting in corneal endothelial dysfunction which is characterized by corneal edema, bullous keratopathy, and loss of visual acuity 2 . Human CECs have limited proliferative capacity in vivo and cannot be subcultured for more than a few passages in vitro 3,4 . Corneal transplantation is the only solution at present. However, corneal transplantation requires a fresh human cornea and there is a worldwide shortage of donors 5 . Therefore, finding new functional CECs to replace human CECs is a new and potential direction for future clinical application.Skin-derived precursors (SKPs) were discovered by Tomas 6,7 , and they have been a research hotspot in recent years. SKPs can be isolated in large quantities from many parts of the skin in rodents and humans. As they are multipotent, they can be differentiated into several functional cell types 8 , and are able to suppress the allogeneic activation of T-lymphocytes resulting in an improved health status of animals suffering from a graft-versus-host reaction 9 . Moreover, SKPs were demonstrated to be embryonic neural-crest-related precursors and share many properties with neural crest stem cells 10

This paper reports the superior properties of a Cu interconnect cosputtered with a minor RenormalNx on barrierless Si. After heating at 730°C for 1h , there is no observable interaction between Cu(normalReNx) and Si. The film remains stable after five cycles of heating at 700°C for a total of 2.5h . The film resistivity is high in the as-deposited condition, and yet it decreases to ∼2.8μΩcm upon heating. The leakage current is about 3 orders of magnitude lower than that of pure Cu. Furthermore, the film adhesion on Si is also improved noticeably. The film is thus useful for advanced barrierless interconnects.

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.

No abstract

Rosmarinic acid (RA) is a naturally occurring polyphenolic compound. It has been reported that RA possessed antioxidant and anti-inflammatory properties. Our previous study showed that RA could protect MES23.5 dopaminergic cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. The purpose of this study was to explore the neuroreparative (neurorescue) effect of RA on 6-OHDA-lesioned rat model of Parkinson's disease (PD) in vivo. In this study, the rats were given RA orally after intrastriatal 6-OHDA lesion. Results showed that the dopamine content in the striatum decreased and the numbers of tyrosine hydroxylase-immunoreactive neurons reduced after 6-OHDA treatment. RA treatment after 6-OHDA administration could restore these changes. Further studies demonstrated that 6-OHDA treatment increased the iron-staining positive cells, which were markedly decreased by RA treatment. Moreover, RA suppressed the increased ratio of Bax/Bcl-2 at gene level induced by 6-OHDA. This indicates that the neurorescue effects of RA against 6-ODHA-induced degeneration of the nigrostriatal dopaminergic system were achieved by decreasing nigral iron levels and regulating the ratio of Bcl-2/Bax gene expression.