We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltage-gated sodium channel (I Na), and the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes rapidly activating delayed rectifier K channels (I Kr). Both ion channels have also been shown to bind to Nedd4-2 via a conserved Proline-Tyrosine (PY) motif in C-terminal with subsequent ubiquitination and degradation by proteasome. Therefore, loss of Nedd4-2 C2 isoform might be involved in electrophysiological impairment under various conditions. We demonstrate here that Nedd4-2 C2 isoform causes cardiac conduction change in resting condition as well as proarrhythmic change after acute myocardial infarction (MI). The Nedd4-2 C2 knockout (KO) mice showed bradycardia, prolonged QRS, QT intervals, and suppressed PR interval in resting condition. In addition, enhancement of T peak/T end interval was found in mice with surgical ligation of the distal left coronary artery. Morphological analyses based on both ultrasonography of the living heart, as well as histopathological findings revealed that Nedd4-2 C2 KO mice show no significant structural changes from wild-type littermates under resting conditions. These results suggested that Nedd4-2 with C2 domain might play an important role in cardio-renal syndrome through post-transcriptional modification of both ENaC and cardiac ion channels, which are critical for kidney and heart functions. Full article

The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake. We found that EPL failed to reduce blood pressure in KO mice with high oral salt intake and upregulated ENaC expression in ASDN. Thus, salt-sensitive hypertension in Nedd4-2 C2 KO was EPL-resistant. Gene expression analyses of laser-captured specimens in ASDN suggested the presence of non-aldosterone-dependent activation of ENaC transcription in ASDN of Nedd4-2 C2 KO mice, which was abolished by amiloride treatment. Our results from Nedd4-2 C2 KO mice suggest that enhanced ENaC gene expression is critically involved in salt-sensitive hypertension under certain conditions of specific enzyme isoforms for their ubiquitination. Full article

The hydrophilic property of cellulose is a key limiting factor for its wide application. Here, a novel solution impregnation pathway was developed to increase the hydrophobic properties of cellulose. When compared with the regenerated cellulose (RC), the composite films showed a decrease in water uptake ability towards water vapor, and an increase of the water contact angle from 29° to 65° with increasing resin content in the composites, with only a slight change in the transmittance. Furthermore, the Young’s modulus value increased from 3.2 GPa (RC film) to 5.1 GPa (RCBEA50 film). The results indicated that the composites had combined the advantages of cellulose and biphenyl A epoxy acrylate prepolymer (BEA) resin. The presented method has great potential for the preparation of biocomposites with improved properties. The overall results suggest that composite films can be used as high-performance packaging materials. Full article

In order to improve the performance of the Bearingless Induction Motor (BIM) under large disturbances (such as parameter variations and load disturbances), an adaptive variable-rated sliding mode controller (ASMC) is designed to obtain better performance of the speed regulation system. Firstly, the $L_1$ norm of state variables is applied to the conventional exponential reaching law and an adaptive variable-rated exponential reaching law is proposed to reduce system chattering and improve bad convergence performance of the sliding mode variable structure. Secondly, an integral sliding-mode hyper plane is produced according to the speed error in speed regulation system of BIM. Current signal is extracted by the combination of the sliding-mode hyper plane, the electromagnetic torque and the equation of motion. Finally, the feedback speed can adjust operating state adaptively according to speed error and make system chattering-free moving. The simulation and experiment results show that the proposed ASMC can not only enhance the robustness of the system’s uncertainties, but also improve the dynamic performance and suppress system chattering. Full article

Background: Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC remains elusive. Methods: The role of smad3 in chemosensitivity of HCC was measured by cell viability, apoptosis, plate colony formation assays and xenograft tumor models. Non-smad signaling was detected by Western blotting to search for the underlying mechanisms. Results: Smad3 enhanced the chemosensitivity of HCC cells to cisplatin. Smad3 upregulated p21^Waf1/Cip1 and downregulated c-myc and bcl2 with the treatment of cisplatin. Moreover, overexpression of smad3 repressed the phosphorylation of AKT, and vice versa. Inhibition of PI3K/AKT pathway by LY294002 restored chemosensitivity of smad3-deficiency cells to cisplatin in HCC. Conclusion: Smad3 sensitizes HCC cells to the effects of cisplatin by repressing phosphorylation of AKT and combination of inhibitor of AKT pathway and conventional chemotherapy may be a potential way to solve drug resistance in HCC. Full article

Liver progenitor cells (LPCs) are activated in chronic liver damage and may contribute to liver fibrosis. Our previous investigation reported that LPCs produced connective tissue growth factor (CTGF/CCN2), an inducer of liver fibrosis, yet the regulatory mechanism of the production of CTGF/CCN2 in LPCs remains elusive. In this study, we report that Activin A is an inducer of CTGF/CCN2 in LPCs. Here we show that expression of both Activin A and CTGF/CCN2 were upregulated in the cirrhotic liver, and the expression of Activin A positively correlates with that of CTGF/CCN2 in liver tissues. We go on to show that Activin A induced de novo synthesis of CTGF/CCN2 in LPC cell lines LE/6 and WB-F344. Furthermore, Activin A contributed to autonomous production of CTGF/CCN2 in liver progenitor cells (LPCs) via activation of the Smad signaling pathway. Smad2, 3 and 4 were all required for this induction. Collectively, these results provide evidence for the fibrotic role of LPCs in the liver and suggest that the Activin A-Smad-CTGF/CCN2 signaling in LPCs may be a therapeutic target of liver fibrosis. Full article

Rainfall-induced soil erosion of a mountain area plays a significant role in supplying sediment and shaping the landscape. The related area of soil erosion, as an index of the changed landscape, is easier to calculate visually using some popular imaging tools. By image analysis, our work shows that the changing of the soil erosion area admits the structure of an S-growth curve. Therefore, we propose to establish an S-curve model, based on incremental learning, to predict the soil erosion area. In the process of incremental learning, we dynamically update the accumulative rainfall and rainfall intensity to train the parameters of our S-curve model. In order to verify our prediction model, the index of area is utilized to express the output of eroded soil in a series of experiments. The results show that the proposed S-growth curve model can be used to estimate the growth of the soil erosion area (average relative error 3%–9.7%) according to variable soil material and rainfall intensity. The original S-growth curve model can calculate the erosion areas of just one soil material and one rainfall condition whose average relative error is 7.5%–12.2%; compared to the simple time series analysis-moving average method (average relative error 5.7%–12.1%), our proposed S-growth curve model can reveal the physical mechanism and evolution of the research object. Full article

Two new indole alkaloids, metagenetriindole A (1) and metagenebiindole A (2), were identified from deep-sea sediment metagenomic clone derived Escherichia coli fermentation broth. The structures of new compounds were elucidated by spectroscopic methods. The two new indole alkaloids demonstrated moderately cytotoxic activity against CNE2, Bel7402 and HT1080 cancer cell lines in vitro. Full article

FengYun-3 (FY-3) Visible Infrared Radiometer (VIRR), along with its predecessor, Multispectral Visible Infrared Scanning Radiometer (MVISR), onboard FY-1C&D have had continuous global observation more than 14 years. This data record is valuable for weather prediction, climate monitoring, and environment research. Data quality is vital for satellite data assimilations in Numerical Weather Prediction (NWP) and quantitative remote sensing applications. In this paper, the accuracies of radiometric calibration for VIRR onboard FY-3A and FY-3B, in thermal infrared (TIR) channels, are evaluated using the Low Earth Orbit (LEO)-LEO simultaneous nadir overpass intercalibration method. Hyperspectral and high-quality observations from Infrared Atmosphere Sounding Instrument (IASI) onboard METOP-A are used as reference. The biases of VIRR measurements with respect to IASI over one-and-a-half years indicate that the TIR calibration accuracy of FY-3B VIRR is better than that of FY-3A VIRR. The brightness temperature (BT) measured by FY-3A/VIRR is cooler than that measured by IASI with monthly mean biases ranging from −2 K to −1 K for channel 4 and −1 K to 0.2 K for channel 5. Measurements from FY-3B/VIRR are more consistent with that from IASI, and the annual mean biases are 0.84 ± 0.16 K and −0.66 ± 0.18 K for channels 4 and 5, respectively. The BT biases of FY-3A/VIRR show scene temperature-dependence and seasonal variation, which are not found from FY-3B/VIRR BT biases. The temperature-dependent biases are shown to be attributed to the nonlinearity of detectors. New nonlinear correction coefficients of FY-3A/VIRR TIR channels are reevaluated using various collocation samples. Verification results indicate that the use of the new nonlinear correction can greatly correct the scene temperature-dependent and systematic biases. Full article

Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis. Full article

Based on simulated reflectance, deep convective clouds (DCC) can be used as an invariant target to monitor the radiometric response degradation of the FY-3A/MERSI (Medium Resolution Spectral Imager) reflective solar bands (RSBs). The long-term response of the MERSI RSBs can easily be predicted using a quadratic fit of the monthly DCC mean reflectance, except for bands 6 and 7, which suffer from instrument anomalies. DCC-based degradations show that the blue bands (λ < 500 nm) and water-vapor bands have degraded significantly, whereas for near-infrared bands, the total degradations in four years are within 3% (excluding bands 3 and 20). For most bands, the degradation rates are greatest during the first year in orbit and decrease over time. The FY-3A/MERSI degradation results derived from DCC are consistent within 2.5%, except for bands, 11, 18 and 19, when compared with Aqua/MODIS(Moderate Resolution Imaging Sepetroradiometer) inter-calibration, multi-site invariant earth target calibration and the CRCS(Chinese Radiometric Calibration Site) Dunhuang desert vicarious calibration methods. Overall, the 2σ/mean degradation uncertainty for most MERSI bands was within 3%, validating the temporal stability of the DCC monthly mean reflectances. The DCC method has reduced the degradation uncertainties for MERSI water vapor bands over other methods. This is a significant advantage of the DCC calibration method. The saturation of some MERSI bands may hinder the effectiveness of the DCC calibration approach. Full article

Two new aromatic compounds, butyl 2,5-dihydroxyphenylacetate (1) and butyl 2-O-β-D-glucopyranosyloxy-5-dihydroxyphenylacetate (2), together with three known ones, methyl 2,5-dihydroxyphenylacetate (3), ethyl 2,5-dihydroxyphenylacetate (4) and 2-O-β-D-glucopyranosyloxy-5-hydroxyphenylacetic acid (5), were isolated from the EtOH extract of the kernel of Entada phaseoloides. The structures of the new compounds were elucidated by MS and NMR experiments. Compounds 1, 3 and 4 displayed potent inhibitory activities against HIV-1 replication, with EC₅₀ values of 9.80 μM, 11.70 μM and 9.93 μM, respectively. Full article

The main purpose of this paper is to establish a signal decomposition system aiming at mixed over-voltages in power systems. In an electric power system, over-voltage presents a great threat for the system safety. Analysis and identification of over-voltages is helpful to improve the stability and safety of power systems. Through statistical analysis of a collection of field over-voltage records, it was found that a kind of complicated signals created by mixing of multiple different over-voltages is difficult to identify correctly with current classification algorithms. In order to improve the classification and identification accuracy of over-voltages, a mixed over-voltage decomposition system based on the atomic decomposition and a damped sinusoid atom dictionary has been established. This decomposition system is optimized by using particle swarm optimization and the fast Fourier transform. Aiming at possible fault decomposition results during decomposition of the over-voltage signal, a double-atom decomposition algorithm is proposed in this paper. By taking three typical mixed over-voltages as examples, the validity of the algorithm is demonstrated. Full article

This paper proposes a simple and effective method for classification of fundamental ferroresonance, single phase-to-ground and wire breakage over-voltages. In isolated neutral networks, power frequency over-voltages due to ferroresonance, single phase-to-ground and wire breakage may exist for a long time, and have very highly similar voltage features. If the improper suppression operation is applied due to incorrect identification, the accident is likely to worsen further. In this paper, the voltage and current features of these faults are analyzed, and a new effective classification criterion for fundamental ferroresonance and single phase-to-ground based on zero sequence current is proposed. A comprehensive identification method based on voltage, current and zero sequence current features is proposed, which is feasible and promising for real applications. Full article