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

Modeling nitrogen loading in a small watershed in southwest China using a DNDC model with hydrological enhancements

The degradation of water quality has been observed worldwide, and inputs of nitrogen (N), along with other nutrients, play a key role in the process of contamination. The quantification of N loading from non-point sources at a watershed scale has long been a challenge. Process-based models have been developed to address this problem. Because N loading from non-point sources result from interactions between biogeochemical and hydrological processes, a model framework must include both types of processes if it is to be useful. This paper reports the results of a study in which we integrated two fundamental hydrologic features, the SCS (Soil Conservation Service) curve function and the MUSLE (Modified Universal Soil Loss), into a biogeochemical model, the DNDC. The SCS curve equation and the MUSLE are widely used in hydrological models for calculating surface runoff and soil erosion. Equipped with the new added hydrologic features, DNDC was substantially enhanced with the new capacity of simulating both vertical and horizontal movements of water and N at a watershed scale. A long-term experimental watershed in Southwest China was selected to test the new version of the DNDC. The target watershed\u27s 35.1 ha of territory encompass 19.3 ha of croplands, 11.0 ha of forest lands, 1.1 ha of grassplots, and 3.7 ha of residential areas. An input database containing topographic data, meteorological conditions, soil properties, vegetation information, and management applications was established and linked to the enhanced DNDC. Driven by the input database, the DNDC simulated the surface runoff flow, the subsurface leaching flow, the soil erosion, and the N loadings from the target watershed. The modeled water flow, sediment yield, and N loading from the entire watershed were compared with observations from the watershed and yielded encouraging results. The sources of N loading were identified by using the results of the model. In 2008, the modeled runoff-induced loss of total N from the watershed was 904 kg N yr−1, of which approximately 67 % came from the croplands. The enhanced DNDC model also estimated the watershed-scale N losses (1391 kg N yr−1) from the emissions of the N-containing gases (ammonia, nitrous oxide, nitric oxide, and dinitrogen). Ammonia volatilization (1299 kg N yr−1) dominated the gaseous N losses. The study indicated that process-based biogeochemical models such as the DNDC could contribute more effectively to watershed N loading studies if the hydrological components of the models were appropriately enhanced

PcP_c states and their open-charm decays with the complex scaling method

A partial width formula is proposed using the analytical extension of the wave function in momentum space. The distinction of the Riemann sheets is explained from the perspective of the Schrodinger equation. The analytical form in coordinate space and the partial width are derived subsequently. Then a coupled-channel analysis is performed to investigate the open-charm branching ratios of the $P_c$ states, involving the contact interactions and one-pion-exchange potential with the three-body effects. The low energy constants are fitted using the experimental masses and widths as input. The $P_c(4312)$ is found to decay mainly to $\Lambda_c\bar{D}^*$, while the branching ratios of the $P_c(4440)$ and $P_c(4457)$ in different channels are comparable. Under the reasonable assumption that the off-diagonal contact interactions are small, the $J^P$ quantum numbers of the $P_c(4440)$ and the $P_c(4457)$ prefer $\frac{1}{2}^-$ and $\frac{3}{2}^-$ respectively. Three additional $P_c$ states at 4380 MeV, 4504 MeV and 4516 MeV, together with their branching ratios, are predicted. A deduction of the revised one-pion-exchange potential involving the on-shell three-body intermediate states is performed.Comment: 16 pages, 5 figure

Comparing the contribution of visible-light irradiation, gold nanoparticles, and titania supports in photocatalytic nitroaromatic coupling and aromatic alcohol oxidation

Under visible-light irradiation, gold nanoparticles (Au NPs) supported by titania (TiO₂) nanofibers show excellent activity and high selectivity for both reductive coupling of nitroaromatics to corresponding azobenzene or azoxylbenzene and selective oxidation of aromatic alcohols to corresponding aldehydes. The Au NPs act as active centers mainly due to their localized surface plasmon resonance (LSPR) effect. They can effectively couple the photonic energy and thermal energy to enhance reaction efficiency. Visible-light irradiation has more influence on the reduction than on the oxidation, lowering the activation energy by 24.7 kJ mol⁻¹ and increasing the conversion rate by 88% for the reductive coupling, compared to merely 8.7 kJ mol⁻¹ and 46% for the oxidation. Furthermore, it is found that the conversion of nitroaromatics significantly depends on the particle size and specific surface area of supported Au NPs; and the catalyst on TiO₂(B) support outperforms that on anatase phase with preferable ability to activate oxygen. In contrast, for the selective oxidation, the effect of surface area is less prominent and Au NPs on anatase exhibit higher photo-catalytic activity than other TiO₂ phases. The catalysts can be recovered efficiently because the Au NPs stably attach to TiO₂ supports by forming a well-matched coherent interface observed via high-resolution TEM

ZcsZ_{cs}, ZcZ_c and ZbZ_b states under the complex scaling method

We investigate the $Z_b$, $Z_c$ and $Z_{cs}$ states within the chiral effective field theory framework and the $S$-wave single channel molecule picture. With the complex scaling method, we accurately solve the Schr\"odinger equation in momentum space. Our analysis reveals that the $Z_b(10610)$, $Z_b(10650)$, $Z_c(3900)$ and $Z_c(4020)$ states are the resonances composed of the $S-$wave $(B\bar{B}^{*}+B^{*}\bar{B})/\sqrt{2}$, $B^{*}\bar{B}^*$, $(D\bar{D}^{*}+D^{*}\bar{D})/\sqrt{2}$ and $D^{*}\bar{D}^*$, respectively. Furthermore, although the $Z_{cs}(3985)$ and $Z_{cs}(4000)$ states exhibit a significant difference in width, these two resonances may originate from the same channel, the $S-$wave $(D_{s}\bar{D}^{*}+D_{s}^{*}\bar{D})/\sqrt{2}$. Additionally, we find two resonances in the $S-$wave $D_s^*\bar{D}^*$ channel, corresponding to the $Z_{cs}(4123)$ and $Z_{cs}(4220)$ states that await experimental confirmation.Comment: 10 pages, 5 figures, 4 table

Tcc+T_{cc}^+ and X(3872)X(3872) with the complex scaling method and DD(Dˉ)πDD(\bar{D})\pi three-body effect

We use the leading order (LO) contact interactions and OPE potentials to investigate the newly observed double-charm state $T_{cc}^+$. The $DD\pi$ three-body effect is important in this system since the intermediate states can go on shell. We keep the dependence of the pion propagators on the center-of-mass energy, which results in a unitary cut of the OPE potential at the $DD\pi$ three-body threshold. By solving the complex scaled Schr\"odinger equation, we find a pole corresponding to the $T_{cc}^+$ on the physical Riemann sheet. Its width is around 80 keV and nearly independent of the choice of the cutoff. Assuming the $D\bar{D}\pi$ and $D\bar{D}^*$ channels as the main decay channels, we apply the similar calculations to the $X(3872)$, and find its width is even smaller. Besides, the isospin breaking effect is significant for the $X(3872)$ while its impact on the $T_{cc}^+$ is relatively small.Comment: 25 pages, 10 figures, 6 table

The effect of motivation and positive affect on ego depletion: Replenishment versus release mechanism

In this study, 2 experiments were conducted to investigate whether motivation and positive affect can alleviate ego depletion and to elucidate their possible mechanisms. In Experiment 1, a crossing-out-letter task was adapted to reach an ego depletion state for Chinese participants. Participants were then randomly assigned to the extrinsic motivation group, the positive affect group or the depletion control group. After the experimental treatment, a dumbbell task was used to measure participants\u27 remaining self-regulatory resources. The results showed that participants in the motivation and positive affect groups performed better on the dumbbell task than participants in the depletion control group. Experiment 2 was similar to Experiment 1 except that participants were asked to perform an additional unexpected dumbbell task after a neutral video following the above procedure. The results of Experiment 1 were replicated; however, participants\u27 performance on the additional dumbbell task differed. The positive affect group performed better than the depletion control group, indicating an increase in self-regulatory resources and thus supporting the replenishment effect of positive affect. No significant difference was found between the motivation group and the depletion control group