Probing Interfacial Aging of Model Adhesion Joints under a Hygrothermal Environment at a Molecular Level.

Generally, for adhesive joints, the polar water molecules in humid environments can have a critical effect on the interfacial structures and structural evolution adjacent to the solid substrates. Regarding this, it is still a big challenge to detect and understand the interfacial hygrothermal aging process at the molecular level in real time and in situ. In this study, to trace the interfacial hygrothermal aging process of a classical epoxy formula containing diglycidyl ether of biphenyl A (DGEBA) and 2,2'-(ethylenedioxy) diethylamine (EDDA) with sapphire and fused silica in a typical hygrothermal environment (85 °C and 85% RH), sum frequency generation (SFG) vibrational spectroscopy was used to probe the molecular-level interfacial structural change over the time. The structural evolution dynamics at the buried epoxy/sapphire and epoxy/silica interfaces upon hygrothermal aging were revealed directly in situ. The interfacial delamination during hygrothermal aging was also elucidated from the molecular level. Upon hygrothermal aging, the interfacial CH signals, such as the ones from methyl, methylene, and phenyl groups, decreased significantly and the water OH signals increased substantially, indicating the water molecules had diffused into the interfaces and destroyed the original interactions between the epoxy formula and the substrates. Further analysis indicates that when the integrated signals in the CH range declined to their minimum and leveled off, the interfacial delamination happened. The tensile experiment proved the validity of these spectroscopic experimental results. Our study provides first-hand and molecular-level evidence on a direct correlation between the diffusion of the surrounding water molecules into the interface and the evolution/destruction of the interfacial structures during hygrothermal aging. More importantly, it is proved, SFG can be developed into a powerful tool to noninvasively reveal the local interfacial delamination in real time and in situ under extreme hygrothermal conditions, complemented by the mechanic test.

Caveolae and the oxidative stress response.

Oxidative stress is a feature of many disease conditions. Oxidative stress can activate a number of cellular pathways leading to cell death, including a distinct iron-dependent pathway involving lipid peroxidation, termed ferroptosis, but cells have evolved complex mechanisms to respond to these stresses. Here, we briefly summarise current evidence linking caveolae to the cellular oxidative stress response. We discuss recent studies in cultured cells and in an in vivo model suggesting that lipid peroxidation driven by oxidative stress causes disassembly of caveolae to release caveola proteins into the cell where they regulate the master transcriptional redox controller, nuclear factor erythroid 2-related factor 2. These studies suggest that caveolae maintain cellular susceptibility to oxidative stress-induced cell death and suggest a crucial role in cellular homeostasis and the response to wounding.

Caveolae sense oxidative stress through membrane lipid peroxidation and cytosolic release of CAVIN1 to regulate NRF2.

Caveolae have been linked to many biological functions, but their precise roles are unclear. Using quantitative whole-cell proteomics of genome-edited cells, we show that the oxidative stress response is the major pathway dysregulated in cells lacking the key caveola structural protein, CAVIN1. CAVIN1 deletion compromised sensitivity to oxidative stress in cultured cells and in animals. Wound-induced accumulation of reactive oxygen species and apoptosis were suppressed in Cavin1-null zebrafish, negatively affecting regeneration. Oxidative stress triggered lipid peroxidation and induced caveolar disassembly. The resulting release of CAVIN1 from caveolae allowed direct interaction between CAVIN1 and NRF2, a key regulator of the antioxidant response, facilitating NRF2 degradation. CAVIN1-null cells with impaired negative regulation of NRF2 showed resistance to lipid-peroxidation-induced ferroptosis. Thus, caveolae, via lipid peroxidation and CAVIN1 release, maintain cellular susceptibility to oxidative-stress-induced cell death, demonstrating a crucial role for this organelle in cellular homeostasis and wound response.

Multicolor Mechanochromic Epoxy Thermosets That Recognize the Intensity, Type, and Duration of Mechanical Stimulation.

Mechanochromic polymers that exhibit multiple color changes under external mechanical stimulation show great potential for sensor applications. Herein, an epoxy thermoset that can reveal the intensity, type, and duration of mechanical stimulation via a combination of disulfide (DS) and rhodamine (Rh) mechanochromophores is reported. A unique multicolor transition occurs upon ball mill or manual grinding because of the different activation energies of DS and Rh. The epoxy changes color depending on the ball mill grinding duration. Simultaneous activation occurs with a mechanochromic time lag between DS and Rh, and the collision energy strongly affects the relative intensity. A more dramatic multicolor response is observed using a mortar and pestle, as sequential activation occurs upon gentle and strong grinding. Various types of mechanical stimulation can cause different aggregates of the activated Rh moiety and vary the relative mechanosensitivities of Rh and DS, which lead to a different color response.

Spectroscopically Detecting Molecular-Level Bonding Formation between an Epoxy Formula and Steel.

The formation of the interfacial adhesion between an epoxy adhesive and a substrate was normally accompanied by the epoxy curing process on the substrate. Although the debate on the formation mechanism of the interfacial adhesion is still ongoing, this issue can causally be resolved by studying the interfacial structural formation between the epoxy adhesive and the substrate. Herein, to reveal the interfacial structural formation of a representative formula composed of epoxy (digylcidyl ether of biphenyl A, DGEBA) and amine hardener (2,2'-(ethylenedioxy) diethylamine, EDDA) with the steel substrate upon curing and postcuring treatments, sum-frequency generation (SFG) vibrational spectroscopy with a sandwiched transparent window/epoxy adhesive/steel setup was applied to detect and track the buried molecular-level structures at the epoxy adhesive/steel interface. An X-ray photoelectron spectroscopic (XPS) experiment was performed to probe the intentionally exposed interface to disclose the occurring interfacial chemical reaction. The reaction between the epoxy groups and the steel-surface OH groups and the molecular reconstruction of interfacial epoxy methyl groups upon curing and postcuring steps were confirmed. The latter also indirectly indicated the formation of the additional hydrogen bonding and the former bonding reaction at the interface. The above two spectroscopic experimental results matched up with the further examination of the adhesion strength. Therefore, this work elucidates the formation of the interfacial bonding between the epoxy formula and the steel substrate upon curing and postcuring treatments at the molecular level, thus providing an in-depth insight into the origin of the interfacial adhesion.

Molecular-Level Correlation between Spectral Evidence and Interfacial Bonding Formation for Epoxy Adhesives on Solid Substrates.

Interfacial bonding strength of an epoxy-based adhesive depends on the interfacial interaction between the adhesive and the substrate. Normally, the curing process at the interface accompanied by the interfacial bonding formation is different from that in the bulk, and it is still a big challenge to probe the interfacial bonding formation at a molecular level. In this study, to trace the interfacial structural evolution of a representative formula of epoxy (digylcidyl ether of biphenyl A, DGEBA) and amine hardener [1,2-bis(2-aminoethoxy)ethane, EDDA] with the sapphire and silica substrates upon curing and post-curing steps, sum frequency generation (SFG) vibrational spectroscopy is employed to detect the molecular-level interfacial structural information. For the sapphire substrate, upon curing, backbone methylene (CH2) stretching signals decrease, indicating the formation of a rigid chain network structure and thus losing the local methylene order, while vibrational signals of the sapphire surface hydroxyl (OH) groups (including hydrogen-bonded and unbonded) increase significantly, indicating the formation of a strong hydrogen-bonding and polar interaction between the epoxy adhesive and the sapphire surface. Upon post-curing, increased backbone CH2 signals and decreased sapphire OH signals suggest interfacial chemical bonding formation due to the reaction between the epoxy rings and the sapphire surface OH groups. Orientation analysis confirms the enhanced ordering of the sapphire surface OH groups upon curing and post-curing, in comparison to the uncured epoxy formula. As for the fused silica, weak vibrational signals of the methylene (CH2) and methyl (CH3) groups are observed before curing, while both of them increase slightly for the cured and post-cured epoxy formulae, suggesting relatively less hydrophilic nature of the silica surface compared to that of the sapphire surface, also evidenced by the very weak OH signals upon curing and post-curing. Further measurement on the adhesion strength matches up with the above spectroscopic experimental results, substantiating the correlation between the macroscopic bonding strength of the epoxy adhesive and the microscopic molecular-level structure.

Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response.

Caveolae-associated protein 3 (cavin3) is inactivated in most cancers. We characterized how cavin3 affects the cellular proteome using genome-edited cells together with label-free quantitative proteomics. These studies revealed a prominent role for cavin3 in DNA repair, with BRCA1 and BRCA1 A-complex components being downregulated on cavin3 deletion. Cellular and cell-free expression assays revealed a direct interaction between BRCA1 and cavin3 that occurs when cavin3 is released from caveolae that are disassembled in response to UV and mechanical stress. Overexpression and RNAi-depletion revealed that cavin3 sensitized various cancer cells to UV-induced apoptosis. Supporting a role in DNA repair, cavin3-deficient cells were sensitive to PARP inhibition, where concomitant depletion of 53BP1 restored BRCA1-dependent sensitivity to PARP inhibition. We conclude that cavin3 functions together with BRCA1 in multiple cancer-related pathways. The loss of cavin3 function may provide tumor cell survival by attenuating apoptotic sensitivity and hindering DNA repair under chronic stress conditions.

When cells become cancerous they often stop making certain proteins. This includes a protein known as cavin3 which resides in bulb-shaped pits of the membrane that surrounds the cell called caveolae. These structures work like stress detectors, picking up changes in the membrane and releasing proteins, such as cavin3, into the cell's interior. Past studies suggest that cavin3 might interact with a protein called BRCA1 that suppresses the formation of tumors. Cells with mutations in the gene for BRCA1 struggle to fix damage in their DNA, and have to rely on other repair proteins, such as PARPs (short for poly (ADP-ribose) polymerases). Blocking PARP proteins with drugs can kill cancer cells with problems in their BRCA1 proteins. However, it was unclear what role cavin3 plays in this mechanism. To investigate this, McMahon et al. exposed cells grown in the laboratory to DNA-damaging UV light to stimulate the release of cavin3 from caveolae. This revealed that cavin3 interacts with BRCA1 when cells are under stress, and helps stabilize the protein so it can perform DNA repairs. Cells without cavin3 showed decreased levels of the BRCA1 protein, but compensated for the loss of BRCA1 by increasing the levels of their PARP proteins. These cells also had increased DNA damage following treatment with drugs that block PARPs, similar to cancer cells carrying mutations in the gene for BRCA1. These findings suggest that cavin3 helps BRCA1 to suppress the formation of tumors, and therefore should be considered when developing new anti-cancer treatments.

An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells.

CAV1 (caveolin 1) expression and secretion is associated with prostate cancer (PCa) disease progression, but the mechanisms underpinning CAV1 release remain poorly understood. Numerous studies have shown CAV1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) CAV1 topology. Here we show that CAV1 can be secreted from specific PCa types in an inverted vesicle-associated form consistent with the features of bioactive CAV1 secretion. Characterization of the isolated vesicles by electron microscopy, single-molecule fluorescence microscopy and proteomics reveals they represent a novel class of exosomes ~40 nm in diameter containing ~50-60 copies of CAV1 and, strikingly, are released via a non-canonical secretory macroautophagy/autophagy pathway. This study provides novel insights into a mechanism whereby CAV1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression.Abbreviations: 3-MA: 3-methyladenine; APEX: a modified soybean ascorbate peroxidase; ATG5: autophagy related 5; ATG9A: autophagy related 9A; ATG12: autophagy related 12; BHK: baby hamster kidney; C-exosomes: caveolin-exosomes; CAMKK2/CAMKKß: calckum/calmodulin dependent protein kinase kinase 2; CAV1: caveolin 1; DAB: 3,3'-diaminobenzidine; DAPK: death associated protein kinase; EEA1: early endosome antigen 1; EM: electron microscopy; FCS: fluorescence correlation spectroscopy; GBP: GFP/YFP-binding peptide; GFP: green fluorescent protein; GOLGA2: golgin A2; ILVs: intralumenal vesicles; LC3: microtubule-associated protein 1 light chain 3; MBP: maltose binding protein; MTORC1: mechanistic target of rapamycin kinase complex 1; MVBs: multivesicular bodies; PBS: phosphate-buffered saline; PCa: prostate cancer; PI3K: phosphoinositide 3-kinase; PM: plasma membrane; SFM: serum-free medium; TSG101: tumor susceptibility 101; WCL: whole cell lysates; WT: wild type; YFP: yellow fluorescent protein; ßoG: ß-octylglucoside.

Caveolae: Formation, dynamics, and function.

Caveolae are abundant surface pits formed by the assembly of cytoplasmic proteins on a platform generated by caveolin integral membrane proteins and membrane lipids. This membranous assembly can bud off into the cell or can be disassembled releasing the cavin proteins into the cytosol. Disassembly can be triggered by increased membrane tension, or by stress stimuli, such as UV. Here, we discuss recent mechanistic studies showing how caveolae are formed and how their unique properties allow them to function as multifunctional protective and signaling structures.

Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis.

Caveolae are specialized domains of the plasma membrane. Formation of these invaginations is dependent on the expression of Caveolin-1 or -3 and proteins of the cavin family. In response to stress, caveolae disassemble and cavins are released from caveolae, allowing cavins to potentially interact with intracellular targets. Here, we describe the intracellular (non-plasma membrane) cavin interactome using biotin affinity proteomics and mass spectrometry. We validate 47 potential cavin-interactor proteins using a cell-free expression system and protein-protein binding assays. These data, together with pathway analyses, reveal unknown roles for cavin proteins in metabolism and stress signaling. We validated the interaction between one candidate interactor protein, protein phosphatase 1 alpha (PP1α), and Cavin-1 and -3 and show that UV treatment causes release of Cavin3 from caveolae allowing interaction with, and inhibition of, PP1α. This interaction increases H2AX phosphorylation to stimulate apoptosis, identifying a pro-apoptotic signaling pathway from surface caveolae to the nucleus.

Structure-controlled Co-Al layered double hydroxides/reduced graphene oxide nanomaterials based on solid-phase exfoliation technique for supercapacitors.

High-efficient nanosheets exfoliation and ordered controlled stacking are in urgent need of work for electrochemistry application. Here, we have developed a high-efficient and environmentally-friendly solid-phase method for the exfoliation of Co-Al layered double hydroxide (Co-Al LDH) and graphene oxide (GO). Meanwhile, we found that there is a dynamic structure evolution in the self-assembly process between Co-Al LDH-NS and GO-NS and new theoretical structure models were proposed. With the reduction treatment, the electrochemical test results show that Co-Al LDH/rGO-3 with ideal tiling structure has better electrochemical performance, which provides a specific capacitance of 1492 F g-1 at 1 A g-1 and remains the capacitance retention at approximately 94.3% after 5000 cycles. Moreover, an energy density of 44.6 Wh kg-1 is obtained at a power density of 799.6 W kg-1. The proposed method and the structure-relationship are practically applicable for other 2D materials in the asymmetric supercapacitors.

Controlled Self-Assembled NiFe Layered Double Hydroxides/Reduced Graphene Oxide Nanohybrids Based on the Solid-Phase Exfoliation Strategy as an Excellent Electrocatalyst for the Oxygen Evolution Reaction.

Layered double hydroxides (LDHs), as an effective oxygen evolution reaction (OER) electrocatalyst, face many challenges in practical applications. The main obstacle is that bulk materials limit the exposure of active sites. At the same time, the poor conductivity of LDHs is also an important factor. Exfoliation is one of the most direct and effective strategies to increase the electrocatalytic properties of LDHs, leading to exposure of many active sites. However, developing an efficient exfoliation strategy to exfoliate LDHs into stable monolayer nanosheets is still challenging. Therefore, we report a new and efficient solid-phase exfoliation strategy to exfoliate NiFe LDH and graphene oxide (GO) into monolayer nanosheets and the exfoliating ratios of NiFe LDH and GO can reach up to 10 and 5 wt %, respectively. Based on the solid-phase exfoliation strategy, we accidentally discovered that there is a dynamic evolution process between NiFe-LDH nanosheets (NiFe-LDH-NS) and GO nanosheets (GO-NS) to assemble new NiFe-LDH/GO nanohybrids, i.e., NiFe-LDH-NS could be horizontal bespreading on GO-NS or well-organized standing on GO-NS, or both simultaneously. The electrocatalytic OER property test results show that NiFe-LDH/RGO-3 (NFRG-3) nanohybrids obtained by the reduction treatment of NiFe-LDH/GO-3 (NFGO-3) nanohybrids, in which NiFe-LDH-NS are well-organized standing on GO-NS, have excellent electrocatalytic properties for OER in an alkaline solution (with a small overpotential of 273 mV and a Tafel slope of 49 mV dec-1 at the current density of 30 mA cm-2). The excellent electrocatalytic properties for OER of NFRG-3 nanohybrids could be attributed to the unique three-dimensional arraylike structure with many active sites. At the same time, reduced graphene oxide (RGO) with excellent conductivity can improve the charge-transfer efficiency and synergistically improve OER properties of nanohybrids.

Rapid Stress Relaxation and Moderate Temperature of Malleability Enabled by the Synergy of Disulfide Metathesis and Carboxylate Transesterification in Epoxy Vitrimers.

Vitrimers make up a class of polymeric materials combining the advantages of thermosets and thermoplastics, because they can be reprocessed while being at the same time permanently cross-linked. However, a long heating duration or an elevated temperature is necessary for most vitrimers to relax the stress from deformation and exhibit malleability. Herein, a disulfide-containing carboxylic acid is applied as a curing agent to synthesize epoxy vitrimers with simultaneous disulfide metathesis and carboxylate transesterification. The insoluble networks exhibit rapid stress relaxation and have relaxation times ranging from 1.5 s (200 °C) to 5500 s (60 °C), while the temperature of malleability is as low as 65 °C. Moreover, this vitrimer can be efficiently reprocessed at 100 °C in 1 h with full recovery of mechanical strength for at least four cycles. Additionally, such a material is simply synthesized from commercially available chemicals and may have potential applications in the electronics industry where a high temperature is not allowed.

Rational Design of Peptide-Functionalized Poly(Methacrylic Acid) Brushes for On-Chip Detection of Protease Biomarkers.

There is an increasing demand for developing new materials and approaches for rapid and sensitive detection of protease biomarkers. Herein, the poly(methacrylic acid) (PMAA) brushes were synthesized from silica nanoparticles via surface-initiated atom transfer radical polymerization (ATRP), and flexibly functionalized with different fluorescein-labeled peptides, serving as the substrates for protease assay. To facilitate the point-of-care detection of protease, polyacrylamide gel pad arrays were fabricated to allow permeation of fluorescein-labeled peptide fragments cleaved from the PMAA brushes. This experimental setup enables an on-chip protease assay with an adequate limit of detection (LOD) for detecting trypsin in a buffer solution (3.9 pM) or in serum (1.4 nM) and good specificity for differentiation of trypsin and chymotrypsin. By using this experimental setup, matrix metalloproteinase-2 and matrix metalloproteinase-9 can be detected with LODs of 2.5 nM and 3.3 nM, respectively. Moreover, by introducing an adamantine (Ad) motif to the side-chain of the peptide fragment and ß-cyclodextrin (ß-CD) groups to the gel pad matrix, a 2.2-fold lower LOD was achieved for the detection of trypsin (1.8 pM) due to the supramolecular self-assembly of Ad and ß-CD. Given the advances in the ease of sample handling, this rational design of peptide-functionalized PMAA brushes could be useful for on-chip detection of protease biomarkers or the screening of potential protease inhibitors.

Bio-inspired semi-transparent silver nanowire conductor based on a vein network with excellent electromechanical and photothermal properties.

A bio-inspired conductive binary-network of vein-silver nanowires (AgNWs) was embedded in poly(dimethylsiloxane) (PDMS) to prepare a semi-transparent stretchable conductor (vein-AgNWs-PDMS) by a simple dipping process. The special conductive structure was constructed by using veins with a porous structure as an ideal skeleton to load AgNW networks, which allowed the vein-AgNWs-PDMS composite to show a low sheet resistance of 1 Ω sq-1 with 74% transmittance. The figure of merit of vein-AgNWs-PDMS is as high as 2502 and can be adjusted easily by controlling the times of the dipping cycle. Furthermore, the vein-AgNWs-PDMS conductor can retain high conductivity after 150% mechanical elongation and exhibit excellent electromechanical stability in repeated stretch/release tests with 60% strain (500 cycles). As an example of an application, patterned light-emitting diode (LED) arrays using the vein-AgNWs-PDMS conductors have been fabricated, and worked well under deformation. Moreover, the photo-thermal properties of the vein-AgNWs-PDMS composite have been demonstrated by a position heating experiment using near-infrared (NIR) laser irradiation and the generated heat can be effectively dissipated through the vein network to avoid local overheating. Due to the high-performance and facile fabrication process, the vein-AgNWs-PDMS conductors will have multifunctional applications in stretchable electronic devices.

MDM2 promotes epithelial-mesenchymal transition and metastasis of ovarian cancer SKOV3 cells.

BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated. METHODS: The regulatory effects by MDM2 on cell motility was emulated by wound-healing and transwell assays. The effects on EMT transition and Smad pathway were studied by depicting the expression levels of epithelial marker E-cadherin as well as key components of Smad pathway. To evaluate the clinical relevance of our findings, the correlation of MDM2 expression levels with the stages of 104 ovarian cancer patients was investigated by immunohistochemistry assay. RESULTS: We demonstrate that MDM2 functions as a key factor to drive EMT and motility of ovarian SKOV3 cells, by facilitating the activation of TGF-ß-Smad pathway, which results in the increased transcription of snail/slug and the subsequent loss of E-cadherin levels. Such induction of EMT is sustained in either E3 ligase-depleted MDM2 or E3 ligase inhibitor HLI-373-treated cells, while being impaired by the N-terminal deletion of MDM2, which is also reflected by the inhibitory effects against EMT by Nutlin-3a, the N-terminal targeting agent. The expression levels of MDM2 is highly correlated with the stages of the ovarian cancer patients, and the higher expression of MDM2 together with TGFB are closely correlated with poor prognosis and predict a high risk of ovarian cancer patients. CONCLUSIONS: This study suggests that MDM2 activates Smad pathway to promote EMT in ovarian cancer metastasis, and targeting the N-terminal of MDM2 can reprogram EMT and impede the mobility of cancer cells.

Versatile Functionalization of Poly(methacrylic acid) Brushes with Series of Proteolytically Cleavable Peptides for Highly Sensitive Protease Assay.

The development of new materials for fast and sensitive protease assay is in demand for timely diagnosis of diseases, such as cardiovascular disease, cancers, and Alzheimer disease. Herein, poly(methacrylic acid) (PMAA) brushes were synthesized from the surfaces of silica nanoparticles via surface-initiated atom transfer radical polymerization (ATRP), and functionalized with series of proteolytically cleavable peptides for highly sensitive protease assay. Upon the proteolytic cleavage of the peptides, a short peptide fragment with fluorescent tag (GGK-FITC) is released to the solution, which can be easily detected with a benchtop fluorescence microscope. The grafting densities of PMAA brushes and peptides can be readily tuned by controlling the monomer concentrations of sodium methacrylate in the ATRP reaction. Because of the three-dimensional architecture of PMAA brushes, the loading amount of peptides can reach 21.4% of the total weight of functionalized silica particles (22.4 peptides/nm2), which is much higher than direct immobilization on silica nanoparticles without polymer brushes. Because of the high loading density of peptides, the limit of detection (LOD) of trypsin can reach 1.4 pM in buffer solution or 2.6 nM in nondiluted serum. By rational design of peptide substrates, the peptide-functionalized PMAA brushes can be readily expanded to detect other proteases, such as matrix metalloproteinase-2 (MMP-2), a virtual biomarker for many cancers, with an LOD of 1.1 pM. The proteolytically cleavable peptide-functionalized PMAA brushes offer a starting point for fast and sensitive protease assay.

Optically binary liquid crystalline blue phases induced by one-armed cholesterol-linked azobenzene molecules.

A series of one-armed cholesterol-linked azobenzene molecules named CholXAzo with different spacers were synthesized, in which Chol6Azo was found to have induced blue phases (BPs) with a concentration of 4.0 wt%. Under irradiation of 385 nm UV light with a density of 15.0 mW cm(-2), photo-responsive behaviour of the 4.0 wt% Chol6Azo doped sample named B3 shows a sensitive temperature dependence, which means that at 38.0 °C a phase transition from BPs to the isotropic phase is induced; however, at 33.0 °C, this phase transition does not take place. Results from the research show that the optically binary phase transition behaviour of B3 is sensitive to the isomerization degree of Chol6Azo, which is closely related to the stability of the BP structure and there is a critical isomerization degree of 13.7% for the phase transition of the B3 liquid crystals. Further POM observation shows that the liquid crystal samples doped with different concentrations of Chol6Azo have an increasing transition temperature for photo-induced phase transition from the BP to the isotropic phase along with the increasing concentration of Chol6Azo, which are found to have the same changing tendency with phase transition temperature from the isotropic phase to BPs and a phase diagram is made to map the optically binary behaviour of Chol6Azo doped blue phase liquid crystals. At last, a simple pattern with the BP and the isotropic phase arranged at an interval was made in this optically binary liquid crystalline blue phase under a suitable photomask.

Nutlin-3 inhibits epithelial-mesenchymal transition by interfering with canonical transforming growth factor-ß1-Smad-Snail/Slug axis.

Enormous efforts have been made to explore small molecules that interfere with the TGF-ß signaling pathway, so as to inhibit EMT and the cancer metastasis, but few agents have been identified. In this study, we demonstrated that Nutlin-3 could abolish the down-regulation of E-cadherin induced by TGF-ß1 in p53-deficient cancer cells. Further studies revealed that Nutlin-3 prohibited EMT by blocking the phosphorylation of Smad2/3, resulting in the decreased transcription of Snail/Slug. In addition, Nutlin-3 suppressed the motility of cancer cells, and potentiated the anti-proliferative activity of gefitinib and lapatinib. Collectively, Nutlin-3 could inhibit EMT and enhance the anti-cancer activity of EGFR inhibitors by interfering with the canonical TGF-ß1-Smad-Snail/Slug axis, in a p53-independent manner.