Angiogenesis is a complex process involving endothelial cell migration, proliferation, and differentiation as well as tube formation. These processes are stimulated by a variety of growth factors such as vascular endothelial growth factor (VEGF). VEGF-induced cytoskeletal reorganization plays a crucial role in the angiogenic processes. In the present study, we evaluated the role of calpain in VEGF-induced angiogenesis in vitro and in vivo. Human pulmonary microvascular endothelial cells (PMEC) were incubated with VEGF (10-60 ng/ml) for 2-24 h, after which we measured calpain activities, protein contents of the calpain subunits and of calpastatin, endothelial monolayer wound repair, tube formation, and actin cytoskeleton changes. Incubation of PMEC with VEGF resulted in dose- and time-dependent increases in calpain activity and protein content of calpain-2. VEGF did not change the protein contents of calpain-1 and the small subunit or of calpastatin. Incubation of PMEC with a VEGF receptor blocker prevented the VEGF-induced increase in calpain activity. Inhibition of calpain activity by siRNA directed against calpain-2 and by overexpression of calpastatin prevented VEGF-induced increases in actin stress fibers in endothelial cells and angiogenesis. Overexpression of calpastatin also inhibits vessel formation in subcutaneous (s.c.) matrigel plugs in mice. These results indicate that calpain mediates VEGF-induced angiogenic effects by modulating actin cytoskeletal organization.

c-Myc is a transcriptional factor that functions as a central regulator of cell growth, proliferation, and apoptosis. Overexpression of c-Myc also enhances DNA double-strand breaks (DSBs), genetic instability, and tumorigenesis. However, the mechanism(s) involved remains elusive. Here, we discovered that γ-ray ionizing radiation-induced DSBs promote c-Myc to form foci and to co-localize with γ-H2AX. Conditional expression of c-Myc in HO15.19 c-Myc null cells using the Tet-Off/Tet-On inducible system results in down-regulation of Ku DNA binding and suppressed activities of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and DNA end-joining, leading to inhibition of DSB repair and enhanced chromosomal and chromatid breaks. Expression of c-Myc reduces both signal and coding joins with decreased fidelity during V(D)J recombination. Mechanistically, c-Myc directly interacts with Ku70 protein through its Myc box II (MBII) domain. Removal of the MBII domain from c-Myc abrogates its inhibitory effects on Ku DNA binding, DNA-PKcs, and DNA end-joining activities, which results in loss of c-Myc's ability to block DSB repair and V(D)J recombination. Interestingly, c-Myc directly disrupts the Ku/DNA-PKcs complex in vitro and in vivo. Thus, c-Myc suppression of DSB repair and V(D)J recombination may occur through inhibition of the nonhomologous end-joining pathway, which provides insight into the mechanism of c-Myc in the development of tumors through promotion of genomic instability.

Design and fabrication of freestanding chiro‐photonic crystal film with the ability to change color over the whole visible light spectrum is appealing for anticounterfeiting technology and smart labels. Utilizing a newly synthesized light‐responsive molecular motor functionalized with cholesterol (chol‐MM) on the rotor, novel light‐controlled photonic crystal is prepared by doping the novel chol‐MM into liquid crystals (LCs). Thanks to the liquid crystalline cholesterol substituent, the chol‐MM can be triggered by visible light (420 nm). At the same time, the miscibility of chol‐MM in LC matrix is significantly enhanced. Integrating the chol‐MM with thermochromic hydrogen‐bonded LC matrix, thermal and light dual‐responsive cholesteric LC (CLC) material is prepared, in which the nanoscale helical pitch is tunable by photo‐induced molecular motions of chol‐MM. More importantly, utilizing UV‐initiated polymerization of the visible light‐modulated CLC material, structural colored photonic crystal films with arbitrary colorful patterns are fabricated. Such freestanding helical nanostructured labels have potential in the application of encrypted communication and anticounterfeiting.

Design and fabrication of advanced security label showing superior performance in data encryption has attracted tremendous scientific interests. Especially, multifunctional optical labels capable of storing distinct information in different modes are highly demanded.Here, a fluorescent cholesteric liquid crystalline network (CLCN) film with programmable visible patterns and photo-rewritable fluorescent patterns was designed and prepared. The visible patterns were fixed by helical network and the colors of visible patterns were tunable by changing relative humidity (RH). The fluorescent patterns originated from dynamic isomerization of fluorescent hydrazones, exhibiting highly thermal stability and switching-ability controlled by light. The orthogonal construction of visible and fluorescent pattern enabled the novel CLCN to encrypt distinct information in reflective mode and in emissive mode, indicating its potential in anti-counterfeiting and information encryptions.