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.

Dynamic photonic crystals with tunable structural colors have been a hot topic in the research of anticounterfeiting devices, decoration, and detection. In this work, we prepared cholesteric liquid crystalline network (CLCN)-based photonic crystals that present humidity- and SO2 gas-responsive behaviors. The covalently cross-linked CLCN film presents humidity-responsive color changes due to the swelling/deswelling of the matrix under different humidity conditions. When treating the CLCN film with SO2 gas, the carboxylic salt converted to the acid and the film was not able to respond to the humidity change anymore. The mechanism of the SO2 gas-gated humidity responsiveness of the CLCN film was characterized. It was found that the acidic gas caused changes of pH, resulting in the conversion of the salt to acid and alteration of the surface property. The influence of concentration of SO2 gas and pH on humidity responsiveness of the CLCN film was investigated. We hope that this method provides inspirations for the design and fabrication of visualized pH and acidic gas detectors.

Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na+ and Ca2+ and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca2+ levels ([Ca2+]i), we found that OGD induced a significant higher increase in glutamate-evoked Ca2+ influx compared to untreated control and such an increase was reduced by TRPC6 deletion. Enhancement of TRPC6 expression using AdCMV-TRPC6-GFP infection in WT neurons increased [Ca2+]i in response to glutamate application compared to AdCMV-GFP control. Inhibition of N-methyl-d-aspartic acid receptor (NMDAR) with MK801 decreased TRPC6-dependent increase of [Ca2+]i in TRPC6 infected cells, indicating that such a Ca2+ influx was NMDAR dependent. Furthermore, TRPC6-dependent Ca2+ influx was blunted by blockade of Na+ entry in TRPC6 infected cells. Finally, OGD-enhanced Ca2+ influx was reduced, but not completely blocked, in the presence of voltage-dependent Na+ channel blocker tetrodotoxin (TTX) and dl-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) blocker CNQX. Altogether, we concluded that I/R-induced brain damage was, in part, due to upregulation of TRPC6 in cortical neurons. We postulate that overexpression of TRPC6 following I/R may induce neuronal death partially through TRPC6-dependent Na+ entry which activated NMDAR, thus leading to a damaging Ca2+ overload. These findings may provide a potential target for future intervention in stroke-induced brain damage.

Angiogenesis is meticulously controlled by a fine balance between positive and negative regulatory activities. Vascular endothelial growth factor (VEGF) is a predominant angiogenic factor and its dosage is precisely regulated during normal vascular formation. In cancer, VEGF is commonly overproduced, resulting in abnormal neovascularization. VEGF is induced in response to various stimuli including hypoxia; however, very little is known about the mechanisms that confine its induction to ensure proper angiogenesis. Chromatin insulation is a key transcription mechanism that prevents promiscuous gene activation by interfering with the action of enhancers. Here we show that the chromatin insulator-binding factor CTCF binds to the proximal promoter of VEGF . Consistent with the enhancer-blocking mode of chromatin insulators, CTCF has little effect on basal expression of VEGF but specifically affects its activation by enhancers. CTCF knockdown cells are sensitized for induction of VEGF and exhibit elevated proangiogenic potential. Cancer-derived CTCF missense mutants are mostly defective in blocking enhancers at the VEGF locus. Moreover, during mouse retinal development, depletion of CTCF causes excess angiogenesis. Therefore, CTCF-mediated chromatin insulation acts as a crucial safeguard against hyperactivation of angiogenesis.

Circularly polarized luminescence (CPL)-active materials with high dissymmetry factor (g lum ) values show great potential in photonic devices. In this study, electric-field-driven systems with tunable CPL signals are successfully fabricated based on polymer-stabilized cholesteric liquid crystal (PSChLC) doping by fluorescent molecules. By constructing a gradient helical superstructure of PSChLCs, distinctive CPL emission from two sides of a single sample is realized, in which the |g lum | values were measured to be 0.6 and 1.5, respectively. Herein, we discussed the possible mechanism of this phenomenon. In addition, an applied electric field could broaden the reflection bandwidth of PSChLCs from 150 to 500 nm, covering the whole visible light region. Furthermore, this electric field-induced behavior leads to the variation of CPL signals and corresponding g lum values, indicating the potential of the novel materials in the design and preparation of CPL-emitting devices with electrically tunable CPL intensity and g lum .