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Apelin is an endogenous active peptide, playing a crucial role in regulating cardiovascular homeostasis. This study aimed to investigate the interaction between apelin and endoplasmic reticulum stress (ERS). Tunicamycin (Tm) and dithiothreitol (DTT) were used to induce ERS in the ex vivo cultured myocardium of rats. Myocardial injury was determined by the activities of lactate dehydrogenase and creatine kinase-MB in the culture medium. The protein levels of an ERS-associated molecule, apelin, and its receptor angiotensin domain type 1 receptor-associated proteins (APJ) in the myocardium were determined by western blot analysis. The level of apelin in the culture medium was determined by enzyme immunoassay. Administration of Tm and DTT triggered ERS activation and myocardial injury, and led to a decrease in protein levels of apelin and APJ, in a dose-dependent manner. Integrated stress response inhibitor, an inhibitor of eukaryotic initiation factor 2α phosphorylation that is commonly used to prevent activation of protein kinase R-like ER kinase cascades, blocked ERS-induced myocardial injury and reduction of apelin and APJ levels. The ameliorative effect of integrated stress response inhibitor was partially inhibited by [Ala]-apelin-13, an antagonist of APJ. Furthermore, apelin treatment inhibited activation of the 3 branches of ERS induced by Tm and DTT in a dose-dependent manner, thereby preventing Tm-induced or DTT-induced myocardial injury. The negative feedback regulation between ERS activation and apelin/APJ suppression might play a critical role in myocardial injury. Restoration of apelin/APJ signaling provides a potential target for the treatment and prevention of ERS-associated tissue injury and diseases.

Runt-related transcription factor 2 (RUNX2) is an osteogenesis-related transcription factor that has emerged as a prominent transcription repressing factor in carcinogenesis. However, the role of RUNX2 in breast cancer metastasis remains poorly understood. Here, we show that RUNX2 recruits the metastasis-associated 1 (MTA1)/NuRD and the Cullin 4B (CUL4B)-Ring E3 ligase (CRL4B) complex to form a transcriptional-repressive complex, which catalyzes the histone deacetylation and ubiquitylation. Genome-wide analysis of the RUNX2/NuRD(MTA1)/CRL4B complex targets identified a cohort of genes including peroxisome proliferator-activated receptor alpha (PPARα) and superoxide dismutase 2 (SOD2), which are critically involved in cell growth, epithelial-to-mesenchymal transition (EMT) and invasion. We demonstrate that the RUNX2/NuRD(MTA1)/CRL4B complex promotes the proliferation, invasion, tumorigenesis, bone metastasis, cancer stemness of breast cancer in vitro and in vivo. Strikingly, RUNX2 expression is upregulated in multiple human carcinomas, including breast cancer. Our study suggests that RUNX2 is a promising potential target for the future treatment strategies of breast cancer.

The biological function of PRMT5 remains poorly understood in cervical cancer metastasis. Here, we report that PRMT5 physically associates with the transcription factor Snail and the NuRD(MTA1) complex to form a transcriptional-repressive complex that catalyzes the symmetrical histone dimethylation and deacetylation. This study shows that the Snail/PRMT5/NuRD(MTA1) complex targets genes, such as TET1and E-cadherin, which are critical for epithelial-mesenchymal transition (EMT). This complex also affects the conversion of 5mC to 5hmC. This study demonstrates that the Snail/PRMT5/NuRD(MTA1) complex promotes the invasion and metastasis of cervical cancer in vitro and in vivo. This study also shows that PRMT5 expression is upregulated in cervical cancer and various human cancers, and the PRMT5 inhibitor EPZ015666 suppresses EMT and the invasion potential of cervical cancer cells by disinhibiting the expression of TET1 and increasing 5hmC, suggesting that PRMT5 is a potential target for cancer therapy.

Chemotherapy-induced hair loss (alopecia) (CIA) remains a major unsolved problem in clinical oncology. CIA is often considered to be a consequence of the antimitotic and apoptosis-promoting properties of chemotherapy drugs acting on rapidly proliferating hair matrix keratinocytes. Here, we show that in a mouse model of CIA, the downregulation of Shh signaling in the hair matrix is a critical early event. Inhibition of Shh signaling recapitulated key morphological and functional features of CIA, whereas recombinant Shh protein partially rescued hair loss. Phosphoproteomics analysis revealed that activation of the MAPK pathway is a key upstream event, which can be further manipulated to rescue CIA. Finally, in organ-cultured human scalp hair follicles as well as in patients undergoing chemotherapy, reduced expression of SHHgene correlates with chemotherapy-induced hair follicle damage or the degree of CIA, respectively. Our work revealed that Shh signaling is an evolutionarily conserved key target in CIA pathobiology. Specifically targeting the intrafollicular MAPK-Shh axis may provide a promising strategy to manage CIA.

Highly ordered structure of catalysts could spring up unique properties in catalytic activities. There is apparently no good reason to disregard the structurally ordered catalyst-amplified chemiluminescence (CL) signals. Herein, we have fabricated the structurally ordered ionic liquid-layered double hydroxide (LDH) assembly through the hydrogen bonding interactions between abundant hydroxyl groups on the surfaces of LDHs and the amino groups in 1-(3-aminopropyl)-3-methyl-imidazolium tetrafluoroborate ([apmim]BF4). Interestingly, we found that the CL signals of luminol–H2O2system in the presence of structurally ordered [apmim]BF4ionic liquid-LDH assembly were extraordinarily enhanced, in comparison with those in the presence of the disordered 1-aminoethyl-3-methyl imidazolium tetrafluoroborate ([aemim]BF4) ionic liquid-LDH assembly. The improved CL performances of the structurally ordered [apmim]BF4ionic liquid-LDH assembly were attributed to the increasing amounts of superoxide anion radicals (O2•–) and hydroxide radicals (•OH) by accelerating of the mass transport from the solution to the surface of ionic liquid–LDH assembly. In addition, such a highly orderly arrangement could increase the emission of the luminol oxidation products by facilitating the electron transfer. Our findings open up new possibilities in the structurally ordered catalyst-enhanced CL emissions, which can be expected to provide a novel and sensitive platform for the CL amplified detection.

Oxygen vacancy is known to act as a reactive center in oxides to produce radicals. Currently, X-ray photoelectron spectra (XPS) become a unique spectral tool for analyzing oxygen vacancy based on the differences in atomic number ratios between metal ions and lattice oxygen. In this work, it was found that the superoxide radical (O2•–)-luminol electrochemiluminescence (ECL) intensity linearly increases with increasing the oxygen vacancy concentrations of TiO2samples coated on the electrodes. An experimental study of the mechanism demonstrates that an increase in oxygen vacancy concentrations could lead to an increase in the generation of O2•–, resulting in an increase in the O2•–-related luminol ECL signals. Accordingly, we have developed a rapid and simple O2•–-luminol ECL platform to detect oxygen vacancy in TiO2samples, based on the relationship between O2•–generation and oxygen vacancy. The proposed ECL platform exhibits good reproducibility and stability through the parallel ECL measurements. Moreover, the feasibility is verified by analyzing the oxygen vacancy concentrations in different TiO2samples with varying the Co, Cr, Fe, and N doping concentrations. The oxygen vacancy concentrations obtained by the proposed ECL method could match well with those obtained by conventional XPS measurements. Our successful construction of the ECL platform will significantly promote the development of the oxygen vacancy detection in oxides and deepen the understanding of the relationship between oxygen vacancy and radicals.

A novel carbon dot-based luminescence probe for singlet oxygen (1O2) with a conventional optical detector has been implemented through the specific formation of electronically excited carbonyls from the breakdown of unstable endoperoxide intermediates, and its application in the real-time in vivomonitoring of 1O2in photodynamic therapy (PDT) is achieved. More attractively, the relationship between the dynamics details of photosensitizer-generated 1O2and the PDT efficacy has been established through a modified multiple-target survival model, enabling a direct and easy estimate of the surviving fraction of tumor cells from the generation dynamics of 1O2. Both in vitroand in vivotherapy results revealed that the rapid generation dynamics of 1O2rather than its cumulative amount is responsible for better treatment efficacy in PDT. Overall, the deeper insight into the important roles of the generation dynamics of 1O2in the PDT efficacy is irreplaceably advantageous in substantially reduced risks from deleterious treatment-related side effects by screening advanced photosensitizers and determining the light exposure end point.

We aimed to investigate whether the facilitating effect of H2S on the baroreceptor reflex is associated with the GABAAreceptor, KATPchannel and L-type Ca2+channel pathway.

The formation of hydroxylated intermediates is the first step in the persulfate-based advanced oxidation processes (AOPs) and depends directly on the oxidation degree of recalcitrant pollutants. Therefore, the monitoring of hydroxylated intermediates plays a vital role in persulfate-based AOPs for evaluating the oxidation degree and understanding the degradation mechanism. In this work, based on the attractive amplification of luminol chemiluminescence (CL) signals by hydroxylated intermediates, we developed a rapid, sensitive, and simple CL-based method to monitor hydroxylated intermediate (i.e., 3,5-diethyl-1,4-benzenediol) generated in persulfate-based AOPs of 1,2-divinylbenzene (DVB). The possible mechanism of the proposed CL system was that hydroxylated intermediates could be oxidized by persulfate in alkaline solution to form superoxide anion radicals and thus lead to an increase in the luminol CL. Finally, the proposed CL system was successfully applied in monitoring hydroxylated intermediates generated during persulfate-based AOPs under different degradation conditions, whose validity and reliability were verified by liquid chromatography–mass spectrometry (LC-MS) and Fourier-transform infrared spectroscopy (FT-IR). The generality of the proposed CL system was verified by monitoring hydroxylated intermediates generated in persulfate-based AOPs of methylbenzene and benzoic acid. These results suggested that this present CL system provided a promising indicator for monitoring hydroxylated intermediates in persulfate-based AOPs.

Background: We aimed to investigate whether the facilitating effect of H2S on the baroreceptor reflex is associated with the GABAAreceptor, KATPchannel and L-type Ca2+channel pathway. Methods: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were used to investigate the facilitating effect of H2S on the baroreceptor reflex by perfusing the isolated carotid sinus. The mechanism by which H2S facilitated the baroreceptor reflex was determined by using Bay K8644 (an agonist of calcium channels), glibenclamide (Gli, a KATPchannel blocker), and picrotoxin (PIC, a blocker of ?-aminobutyric acid [GABAJA receptor). Results: As compared with WKY rats, SHRs showed impaired baroreceptor reflex sensitivity, as demonstrated by a right and upward shift of the functional curve for the intrasinus pressure-arterial blood pressure relation. H2S perfusion (25, 50, or 100 µmol/L) dose-dependently ameliorated the impaired sensitivity of the baroreceptor reflex. Bay K8644 (500nmol/L), Gli (20 µmol/L) and PIC (50µmol/L) all prevented H2S ameliorating the impaired baroreceptor reflex. Conclusions: H2S facilitating the baroreceptor reflex might be associated with activating the GABAAreceptor, opening the KATPchannel, and closing the L-type Ca2+channel. These areas should provide new targets for preventing and treating hypertension.

To improve the poor prognosis of congestive heart failure (CHF), early and accurate diagnosis is necessary. Relaxin is an endogenous cardiovascular peptide, and its plasma level is usually increased in patients with CHF. In this pilot study, we aimed to determine the diagnostic value of relaxin and B-type natriuretic peptide (BNP) in patients with and without CHF.

In this paper, a new zenith tropospheric delay (ZTD) correction model is established by using 4 years of ZTD over Southern California, which not require any meteorological data and only related to the site’s elevation and the day of year. The results show that the stability and precision of the new model are better than Saastamoinen model using ECMWF date, and the precision increases along with increasing site’s elevation. The overall accuracy of the new model is about 3.86cm when used to predict zenith troposhperic delays in 2012 over Southern California area.

The common method to determine Quasi-Geoids is GPS leveling however the Quasi-Geoid of this method determined is a kind of trend surface which not take the physical property of geoid into consideration, and the fitting method is surface fitting which only consider the surveying error, lead to inaccurate fitting result. In allusion to these problems, Remove-restore method is used to remove the long wave information of earth gravity field model to get more smooth residual gravity height anomaly, then compared the influence of different covariance function to the fitting result of least square collocation which take surveying error and model error into account. The results show that Gaussian and resemble Gaussian function can achieve higher fitting precision to the large area with height anomaly value changes significance; the Remove-restore method can effectively improve the fitting precision to least square collocation method which depend on the covariance value of each points.

This paper proposed the optical weighting combined mode of Least Square Support Vector Machine (LS-SVM) and BP Neural network. According to the measured data, this paper compared and analyzed the accuracy of LS-SVM model, BP Neural network model; quadratic polynomial curve surface fitting based on Total least-square algorithm and optimal weighting combined model, the data shows that the optimal weighting combined model has higher precision then others.

In this study, three years of the zenith tropospheric delay (ZTD) data observed from 46 International GNSS system (IGS) sites distributed in Asian area used to assess the effectiveness and accuracy of ZTD calculated from EGNOS model, and the application of the EGNOS model are also analyzed in Asian area. Relative to IGS observed ZTD, the bias and root mean square (RMS) for ZTD calculated from EGNOS model presents an obvious variation in temporal and spatial. These results provide a reference for the study of the tropospheric delay correction model, the real-time GNSS navigation and positioning.

In this paper, the relationship between zenith tropospheric delays and the altitude of stations is analyzed using the EGNOS tropospheric correction model. The new model (EHT model) is proposed for estimating zenith tropospheric delays from regional CORS data without meteorological data. The proposed model is compared with the direct interpolation method and the remove-restore method using data from Guangxi CORS. The results show that the new models significantly improve the calculated precision.

In this paper, the electrical transient mode of synchronous generators is studied, four different simulation model of synchronous generator on sudden short circuit was built, various physical quantities were studied by simulation during the short circuit. By comparing theoretics with simulation, various physical quantities of synchronous generator produced tremendous impact and surge during the sudden circuit and they stabilized in the proceeding state of short circuit. Thoroughly simulation analyzed, the results of simulation are identical with theoretical analysis. The simulation results show that these influence factors should be considered when we design the relay protections.

Background: Alcoholics are at heightened risk for developing active tuberculosis. This study evaluates chronic alcohol consumption in a murine model of vaccination with Mycobacterium bovisBacille Calmette–Guèrin (BCG) and subsequent pulmonary infection with virulent Mycobacterium tuberculosis.

TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. In vivo, the TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Recent work has shown that members of this family, including TACC2, may be involved in the progression of certain solid tumours. The aim of the current study was to identify the role of TACC2 in the TACC2-knockdown breast cancer cell lines. TACC2 expression was examined in human cancer cell lines. TACC2 was experimentally reduced expression in human breast cancer cells. The influence of TACC2 on the biological behavior of breast cancer cells was then investigated in in vitro studies. TACC2 expression showed moderate or high levels in breast cancer cell lines. The reduced expression of TACC2 significantly increased (p < 0.05) the invasive, migratory, growth and adherence properties of the human breast cancer cell lines. Furthermore, PLCγ was expressed at higher levels in TACC2 knockdown breast cancer cell lines. The increased motile pheonotype could be inhibited by the PLCγ inhibitor, which suggested TACC2 could suppress the aggressiveness of breast cancer cells through the PLCγ Pathway. This study shows that TACC2 demonstrates the ability to play a role in governing the metastatic nature of breast cancer cells. The increased motile properties could be regulated via PLCγ signaling pathway in the TACC2 knockdown breast cancer cells. This suggests that TACC2 may function as a tumor suppressor for breast cancer. The findings also suggest that TACC2 may be a potential therapeutic target.

Mesoporous silica nanomaterial is one of the most promising candidates as drug carrier for cancer therapy. Herein, in vitroand in vivostudy of silica nanorattle (SN) with mesoporous and rattle-type structure as a drug delivery system was first reported. Hydrophobic antitumor drug docetaxel (Dtxl) was loaded into the PEGylated silica nanorattle (SN-PEG) with a diameter of 125 nm viaelectrostatic absorption. In human liver cancer cell Hep-G2, the half-maximum inhibiting concentration (IC50) of silica nanorattle encapsulated docetaxel (SN-PEG-Dtxl) was only 7% of that of free Dtxl at 72 h. In vivotoxicity assessment showed that both nanocarrier of silica nanorattle (40 mg/kg, single dose) and SN-PEG-Dtxl (20 mg/kg of Dtxl, three doses) had low systematic toxicity in healthy ICR mice. The SN-PEG-Dtxl (20 mg/kg, intravenously) showed greater antitumor activity with about 15% enhanced tumor inhibition rate compared with Taxotere on the marine hepatocarcinoma 22 subcutaneous model. The results prove that the SN-PEG-Dtxl has low toxicity and high therapy efficacy, which provides convincing evidence for the silica nanorattle as a promising candidate for a drug delivery system.

This article investigates the role of endoplasmic reticulum stress (ERS) in high-glucose-induced vascular smooth muscle cells (VSMCs) calcification and to explore its effects on the expression of GRP78, CHOP, and Caspase-12.VSMCs were treated with high glucose (35 mmoL/L) to induce diabetes to see whether high glucose can induce ERS. Changes in alkaline phosphatase activity, calcium deposition, and runt-related transcription factor 2 (Runx2) were measured. After 5 days’ treatment, the alkaline phosphatase activity, calcium content, and Runx2 expression of the bone differentiation marker protein were all up-regulated in the β-glycerophosphate group, the high-glucose group, and the β-glycerophosphate + high-glucose group when compared with the control group. High-glucose treatment of VSMCs can cause ERS and apoptosis and induces transdifferentiation of VSMCs into osteoblast-like cells, resulting in increased basal phosphatase activity, up-regulation of calcium content, and bone differentiation markers in VSMCs. The findings confirm that ERS plays an important role in the calcification of VSMCs.