Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion.

The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.

Amino acid-based metallo-supramolecular nanoassemblies capable of regulating cellular redox homeostasis for tumoricidal chemo-/photo-/catalytic combination therapy.

Nanozymes, as nanomaterials with natural enzyme activities, have been widely applied to deliver various therapeutic agents to synergistically combat the progression of malignant tumors. However, currently common inorganic nanozyme-based drug delivery systems still face challenges such as suboptimal biosafety, inadequate stability, and inferior tumor selectivity. Herein, a super-stable amino acid-based metallo-supramolecular nanoassembly (FPIC NPs) with peroxidase (POD)- and glutathione oxidase (GSHOx)-like activities was fabricated via Pt4+-driven coordination co-assembly of l-cysteine derivatives, the chemotherapeutic drug curcumin (Cur), and the photosensitizer indocyanine green (ICG). The superior POD- and GSHOx-like activities could not only catalyze the decomposition of endogenous hydrogen peroxide into massive hydroxyl radicals, but also deplete the overproduced glutathione (GSH) in cancer cells to weaken intracellular antioxidant defenses. Meanwhile, FPIC NPs would undergo degradation in response to GSH to specifically release Cur, causing efficient mitochondrial damage. In addition, FPIC NPs intrinsically enable fluorescence/photoacoustic imaging to visualize tumor accumulation of encapsulated ICG in real time, thereby determining an appropriate treatment time point for tumoricidal photothermal (PTT)/photodynamic therapy (PDT). In vitro and in vivo findings demonstrated the quadruple orchestration of catalytic therapy, chemotherapeutics, PTT, and PDT offers conspicuous antineoplastic effects with minimal side reactions. This work may provide novel ideas for designing supramolecular nanoassemblies with multiple enzymatic activities and therapeutic functions, allowing for wider applications of nanozymes and nanoassemblies in biomedicine.

A Modified Langmuir Model for Moisture Diffusion in UGFRE of Composite Insulator Considering the Composite Degradation.

Water invasion induced aging and degradation of the unidirectional glass fiber reinforced epoxy resin (UGFRE) rod is inferred as the primary reason for the decay-like fracture of the composite insulator. In this paper, the moisture diffusion processes in the UGFRE from different directions at various test humidities and temperatures are studied. The moisture diffusion of the UGFRE sample obeys the Langmuir diffusion law under the humidity conditions of 53%, 82% and 100% at 40 °C. In deionized water, the moisture diffusion of the UGFRE sample also obeys the Langmuir diffusion law when the invading direction is vertical to the glass fiber. However, when the water invades the UGFRE sample, parallel with the glass fiber, the weight loss caused by composite degradation should not be neglected. A modified Langmuir model, taking Arrhenius Theory and the nonlinear aging characteristic of the composite into consideration, is proposed and can successfully describe the moisture diffusion process. Both the glass fibers and epoxy resin will degrade in the deionized water. The glass fibers show better resistance to degradation than the epoxy resin. The epoxy resin degrades from the glass fiber/epoxy resin interface and become fragments. For composite insulators, the water invasion through the ends should be avoided as far as possible, or the degradation of the UGFRE rod will result in decay-like fracture.

A Dielectric Polymer/Metal Oxide Nanowire Composite for Self-Adaptive Charge Release.

Electrostatic discharge is a fatal threat to a variety of electronic products. Here we report on a polymer nanocomposite composed of a dielectric polymer embedded with aligned core-shell structured nanowires for highly efficient distributed electrostatic discharge protection. The dielectric nanocomposite is capable of self-adaptive charge release, stemming from the nonlinear interface built in the Bi/Co oxide coated ZnO nanowires that leads to a "hand-in-hand" double-Schottky barrier. The ultralow filler concentration (e.g., 0.5 vol %) endows the nanocomposite with low permittivity (close to the pristine polymer matrix) and high optical transmittance (75%) in the visible light wavelength range, which is desirable in packaging materials and display coatings for portable electronics. The effectiveness for electrostatic discharge protection was validated with an organic light-emitting diode screen protected by the nanocomposite that survived multiple rounds of electrostatic discharge.

Mapping the Space Charge at Nanoscale in Dielectric Polymer Nanocomposites.

Heterogeneous dielectric materials such as dielectric polymer nanocomposites have attracted extensive attention because of their exceptional insulating and dielectric performance, which originates from the unique space charge dynamics associated with the various interfacial regions. However, the space charge distribution and transport in polymer nanocomposites remain elusive due to the lack of analytical methods that can precisely probe the charge profile at the nanoscale resolution. Although a few studies have explored the possibility of using scanning probe techniques for characterizing the local charge distribution, the interference from induced electrical polarization of the material has been unfortunately ignored, leading to inaccurate results. In this contribution, we report an open-loop Kelvin probe force microscopy (KPFM) method with nanoscale resolution for the direct detection of the space charge profile in dielectric polymer nanocomposites. Unlike the conventional studies where a vertical direct current (DC) voltage is applied on the sample through the probe to evoke the charge injection and transport in dielectric polymer nanocomposites, the present method is established based on a delicate electrode configuration where a lateral electric field is allowed to be applied on the sample during the KPFM test. This special testing configuration enables real-time charge injection and transport without inducing the electrical polarization of material along the vertical direction, which gives rise to clean mapping of space charges and reveals the interfacial charge trapping in polymer nanocomposites. This work provides a robust and reliable method for studying the sophisticated charge transport properties associated with the various interfacial regions in heterogeneous dielectric materials.

Universal Phase Transitions of AlB2-Type Transition-Metal Diborides.

High-pressure phase transitions of AlB2-type transition-metal diborides (TMB2; TM = Zr, Sc, Ti, Nb, and Y) were systematically investigated using first-principles calculations. Upon subjecting to pressure, these TMB2 compounds underwent universal phase transitions from an AlB2-type to a new high-pressure phase tP6 structure. The analysis of the atomistic mechanism suggests that the tP6 phases result from atomic layer folds of the AlB2-type parent phases under pressure. Stability studies indicate that the tP6-structured ZrB2, ScB2, and NbB2 are stable and may be observed under high pressure and the tP6-structured TiB2 phase may be recovered at ambient pressure.

Meteorology and ethnicity as critical factors in HRIPT: Comparing responses between Chinese and Indian ethnicities.

BACKGROUND: Human repeated insult patch test (HRIPT) is regarded as one of the confirmatory test in determining the safety of skin sensitizers. A number of important factors should be considered when conducting and interpreting the results of the HRIPT. OBJECTIVE: To investigate for probable critical factors that influence the results of HRIPT with the same protocol in Shanghai and Mumbai. METHODS: Two HRIPTs were carried out in Shanghai and Mumbai in 2011. Six identical products and 1% sodium lauryl sulfate were tested. Two Chinese dermatologists performed the grading in the two cities. Climate conditions of Shanghai and Mumbai were also recorded. RESULTS: For four lower reaction ratio products, cumulative irritation scores in the induction phase were higher in individuals whose ethnicity was Indian rather than Chinese. Reaction ratio of the same four products was highly correlated to the climatic parameters. The other two higher reaction ratio products and the positive control had no difference between the two ethnicities. CONCLUSION: Greater attention ought to be paid to the impact of climate on the results of HRIPT, especially for the mild irritation cosmetics when giving the interpretation. Greater emphasis also needs to be placed on the ethnicity of the subjects.