Tumor-associated EGFR over-expression specifically activates Stat3 and Smad7 resulting in desensitization of TGF-β signaling

Transforming Growth Factor-[beta] (TGF-[beta]) and Epidermal Growth Factor (EGF) signaling pathways are both independently implicated as key regulators in tumor formation and progression. Here, we demonstrate that activation of the tumor-associated and over-expressed EGFR desensitizes TGF-[beta] signaling and its cytostatic regulation through specific Stat3 activation and Smad7 induction. In normal and tumor human cell lines, reduction of TGF-[beta]-mediated Smad2 phosphorylation, nuclear translocation and Smad3 target gene activation were observed where EGFR is over-expressed, but not in cells which expressed EGFR at normal levels. The EGFR downstream signaling molecules phosphatidyinositol-3 Kinase (PI3K) or mitogen-activated protein kinase/ERK kinase (MEK) are not responsible for the down-regulation of TGF-[beta] signaling since blockade of them by specific pharmacological inhibitors LY294002 and U0126 had little effects on the sensitivity of TGF-[beta] signaling. We identified Stat3 as a signaling molecule activated specifically and persistently by over-expressed EGFR, but not by normal levels. Importantly, Stat3 is responsible for the reduced TGF-[beta] sensitivity, since its knockdown by siRNA restored TGF-[beta] signaling sensitivity. Furthermore, over-expressed EGFR, through Stat3 activates Smad7 promoter activity, increasing its protein levels, which is a negative regulator of TGF-[beta] signaling. Consequently, cells were re-sensitized to TGF-[beta] when Smad7 expression was reduced using siRNA. Therefore we establish a novel EGFR-Stat3-Smad7-TGF-[beta] signaling molecular axis where tumor-associated over-expression of EGFR in epithelial cells results in hyperactivation of Stat3, which activates Smad7 expression, compromising the TGF-[beta]'s cytostatic regulation of epithelium and consequent tumor formation

Graphene-plasmon polaritons: From fundamental properties to potential applications

With the unique possibilities for controlling light in nanoscale devices, graphene plasmonics has opened new perspectives to the nanophotonics community with potential applications in metamaterials, modulators, photodetectors, and sensors. This paper briefly reviews the recent exciting progress in graphene plasmonics. We begin with a general description for optical properties of graphene, particularly focusing on the dispersion of graphene-plasmon polaritons. The dispersion relation of graphene-plasmon polaritons of spatially extended graphene is expressed in terms of the local response limit with intraband contribution. With this theoretical foundation of graphene-plasmon polaritons, we then discuss recent exciting progress, paying specific attention to the following topics: excitation of graphene plasmon polaritons, electron-phonon interactions in graphene on polar substrates, and tunable graphene plasmonics with applications in modulators and sensors. Finally, we seek to address some of the apparent challenges and promising perspectives of graphene plasmonics.Comment: Invited minireview paper on graphene plasmon polaritons, 11 pages, 4 figure

Numerical Analysis of Friction power and Wear of Vane in Rotary Compressor

In this article, a numerical method was established to analyze the friction power and wear of vane in the rotary compressor. In this method, the time domain was divided into many steps, the physical process was simplified as an explicit model. At each delta time step, three sub models were calculated iteratively, the geometric model, the contact model and the friction model. Firstly, in the geometric model, geometric kinematics of vane and piston were obtained by calculating multi body dynamical equation. Secondly, in the contact model, Reynolds equation and elastic contact equation were solved as a coupled problem to get the thickness distribution of oil film in the sliding surface. From the oil film thickness distribution, the asperity contact stress and oil film pressure could be obtained, and all other mechanical information could be calculated. Thirdly, in the friction model, the friction power and wear depth distribution were obtained. The friction power was calculated by the time integration of PV value. The PV value was calculated by substituting asperity contact stress and vane sliding velocity. The friction power was input into the Archard wear theory to get the wear depth distribution. Base on this numerical method, the friction power and wear depth distribution of vane friction pairs were got for different rotary compressors in different conditions. Some of the experiments can be replaced by this numerical method, especially the durability experiment. The parametric sensitivity analysis could be done, so, furthermore, it can offer design reference for rotary compressor

The Performance Matching of Inverter Room Air Conditioner

Some key parameter like suction superheat, compressor frequency, indoor and outdoor air volume, have been explored using simulation tools for the performance matching of the inverter room air conditioner. It was found that the all above parameters can be further optimized in every matching condition (including intermediate cooling, rated cooling, maximum cooling, middle heating and rated heating, etc.). The optimum range for all above parameter has been found and can be used in the variable frequency control module to ensure optimal overall performance of the system

Excess Extracellular K\u3csup\u3e+\u3c/sup\u3e Causes Inner Hair Cell Ribbon Synapse Degeneration

Inner hair cell (IHC) ribbon synapses are the first synapse in the auditory system and can be degenerated by noise and aging, thereby leading to hidden hearing loss (HHL) and other hearing disorders. However, the mechanism underlying this cochlear synaptopathy remains unclear. Here, we report that elevation of extracellular K+, which is a consequence of noise exposure, could cause IHC ribbon synapse degeneration and swelling. Like intensity dependence in noise-induced cochlear synaptopathy, the K+-induced degeneration was dose-dependent, and could be attenuated by BK channel blockers. However, application of glutamate receptor (GluR) agonists caused ribbon swelling but not degeneration. In addition, consistent with synaptopathy in HHL, both K+ and noise exposure only caused IHC but not outer hair cell ribbon synapse degeneration. These data reveal that K+ excitotoxicity can degenerate IHC ribbon synapses in HHL, and suggest that BK channel may be a potential target for prevention and treatment of HHL

Growing up with the one-child policy: CEO early-life experiences and corporate investment in China

We examine corporate investment behaviour of Chinese CEOs whose formative years (5–15 years old) overlapped with China’s one-child policy period. We construct alternative measures of CEO early-life experience of gender inequality based on the information on the cities where CEOs lived in their formative years during the one-child policy period. We find that a sample CEO, who experienced greater gender inequality induced by the one-child policy, intends to increase investment, and they invest more than their peers. Moreover, experiencing greater gender inequality, women CEOs are more conservative and risk-averse in investment, and they invest less than their peers. In contrast, men CEOs experiencing greater gender inequality are overconfident and risk-taking in investment, and they invest more than their peers. These results remain robust across a set of tests, including the Generalized Method of Moments (GMM), Difference-In-Difference (DID), and Propensity Score Matching (PSM). We contribute to the debate surrounding China’s one-child policy by providing new evidence on how the one-child policy affects the Chinese economy through its corporate sector

Gap Junction Mediated miRNA Intercellular Transfer and Gene Regulation: A Novel Mechanism for Intercellular Genetic Communication

Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 \u3e Cx26/30 \u3e Cx26 \u3e Cx31 \u3e Cx30 = Cx-null. However, consistent with a uniform structure of miRNAs, there was no significant difference in permeability to different miRNAs. The passage is efficient; the miRNA level in the recipient cells could be up to 30% of the donor level. Moreover, the transferred miRNA is functional and could regulate gene expression in neighboring cells. Connexin mutation and gap junctional blockers could eliminate this miRNA intercellular transfer and gene regulation. These data reveal a novel mechanism for intercellular genetic communication. Given that connexin expression is cell-specific, this connexin-dependent, miRNA intercellular genetic communication may play an important role in synchronizing and coordinating proliferation and differentiation of specific cell types during multicellular organ development

Supramolecular assembly of cucurbit[6]uril and N-butyl-4-pyrrolidinopyridine

The nature of the supramolecular host-guest complex involving 4-pyrrolidinopyridine (BuPC4) and cucurbit[6]uril (Q[6]) has been investigated by NMR and UV spectroscopy, MALDI-TOF mass spectrometry, X-ray crystallography and isothermal titration calorimetry (ITC). The results revealed that the alkyl chain of the guest BuPC4 is located inside the cavity of the Q[6] host, whereas the other section of the BuPC4 guest remains outside of the portal