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In view of the limitations of existing rotating machine fault diagnosis methods in single-scale signal analysis, a fault diagnosis method based on multi-scale permutation entropy (MPE) and multi-channel fusion convolutional neural networks (MCFCNN) is proposed. First, MPE quantitatively analyzes the vibration signals of rotating machine at different scales, and obtains permutation entropy (PE) to construct feature vector sets. Then, considering the structure and spatial information between different sensor measurement points, MCFCNN constructs multiple channels in the input layer according to the number of sensors, and each channel corresponds to the MPE feature sets of different monitored points. MCFCNN uses convolutional kernels to learn the features of each channel in an unsupervised way, and fuses the features of each channel into a new feature map. At last, multi-layer perceptron is applied to fuse multi-channel features and identify faults. Through the health monitoring experiment of planetary gearbox and rolling bearing, and compared with single channel convolutional neural networks (CNN) and existing CNN based fusion methods, the proposed method based on MPE and MCFCNN model can diagnose faults with high accuracy, stability, and speed.

Barium sulfate (BaSO4) is a material with high reflectance for preparing bifunctional sheets used in dry reagent chemical tests. In this study, bifunctional BaSO4 sheets with scattering power and high reflectance were prepared with BaSO4 microspheres sized 1.3~1.8 μm and cellulose acetate (CA). Factors such as the BaSO4 morphology, CA dosage, mixing time, surfactant, solid content and wet sheet thickness were investigated. Scanning electron microscopy (SEM), a dynamic contact angle test, light reflection detector and light reflection densitometer were employed to characterize the structure and properties of bifunctional BaSO4 sheets. The optimal conditions for preparing bifunctional BaSO4 sheets under natural drying conditions were as follows: mass ratio of CA to BaSO4 microspheres was 0.03:1; mixing acetone solution was used to form liquid stock puree; 35 μL Tween-80 was used to improve the hydrophilicity of bifunctional sheets; solid content was 54.9%; mixing 2 h then 450 µm thick sheets were cast on a glass plate using a film applicator. The light reflectance value of bifunctional BaSO4 sheets in the range of 400~800 nm was higher than 97%. Serum diffused in bifunctional BaSO4 sheets reacted in reagent sheets and formed uniform colorful spots. Considering the repeatability of spot proportion and light reflectance value, the sheet offered a uniform serum scattering power and good repeatability. Therefore, the bifunctional BaSO4 sheets are regarded as a promising material for dry chemical diagnostic reagents.

The authors wish to make the following corrections to this paper published in Molecules [...]

Vegetation plays a significant role in controlling soil erosion. However, the effects of each vegetation type on soil erosion have not been fully investigated. In order to explore the influence of multiple vegetation covers on soil erosion and surface runoff generation, 10 different vegetation types, typical of the Nverzhai small basin, have been selected for this study. Regional precipitation, surface runoff, and sediment yield were measured from 2007 to 2018. The wettest year recorded was 2012. Recorded data confirmed that July was the wettest month in this region while January and December were the driest months. Furthermore, surface runoff and sediment yield associated with different vegetation types gradually decreased after 2013, which is the quantification of the consequences due to afforestation processes started in this area. Surface runoff and sediment content recorded for the configuration of sloping farmland were the largest between the different investigated vegetation types. The smallest were the broad-leaved mixed forest, the coniferous mixed forest, and shrubs. Finally, a significant linear positive correlation was found between rainfall and surface runoff, as well as sediment yield (R2 = 0.75). This suggests that climate change implications could be limited by using the more efficient vegetation covering. This research indicates that the ground cover is a key element in controlling soil and water loss, as well as vegetation measures, with high ground cover (i.e., broad-leaved trees). These measures should be strongly recommended for soil erosion control and surface runoff reduction. Moreover, these outcomes can be very helpful for vegetation restoration and water conservation strategies if implemented by local authorities.

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress and induces unfolded protein response (UPR) which are mediated by three transmembrane ER signaling proteins: pancreatic endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). UPR is initiated to protect cells from overwhelming ER protein loading. However, sustained ER stress may result in cell death. ER stress has been implied in various CNS injuries, including brain ischemia, traumatic brain injury, and aging-associated neurodegeneration, such as Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). However, effects of ethanol on ER stress in the CNS receive less attention. In this review, we discuss recent progress in the study of ER stress in ethanol-induced neurotoxicity. We also examine the potential mechanisms underlying ethanol-mediated ER stress and the interaction among ER stress, oxidative stress and autophagy in the context of ethanol neurotoxicity.

The Liangshan pig is a traditional Chinese small-sized breed; it has a relatively long feeding period and low meat production ability but superior meat quality. This study utilized three non-linear growth models (Von Bertalanffy, Gompertz, and logistic) to fit the growth curve of Liangshan pigs from an unselected, random-bred pig population and estimate the pigs most suitable slaughter weight. The growth development data at 20 time points of 275 Liangshan pigs (from birth to 250 d) were collected. To analyze the relative gene expression related to development, seven slaughter weight phases (50, 58, 66, 74, 82, 90, and 98 kg) (20 pigs per phase) were examined. We found that the Liangshan pig growth curve fit the typical S-curve well and that their growth turning point was 193.4 days at a weight of 62.5 kg, according to the best fit Von Bertalanffy model based on the goodness of fit criteria. Furthermore, we estimated that the most suitable slaughter weight was 62.5 to 74.9 kg based on the growth curve and the relative expression levels of growth-related genes.

The Hedgehog (Hh) pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK) is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

HPV-16 long control region (LCR) has been shown to be the most variable region of the HPV-16 genome and may play important roles in viral persistence and the development of cervical cancer. This study aimed to assess the risk of HPV-16 LCR variants for cervical cancer in women of Southwest China. 2146 cervical scrapings of volunteer outpatients and 74 cervical cancer tissues were screened.14 entire HPV-16 LCRs from asymptomatic carriers and 34 entire HPV-16 LCRs from cervical cancer patients were successfully amplified and sequenced to align to others described. 58 different point mutations were detected in 54 nucleotide sites of HPV-16 LCR. G7193T and G7521A variants, accounting for 100% of the infections, were predicted to locate at the binding site for FOXA1 and SOX9, respectively. A7730C variant which showed a high mutation frequency in cervical cancer was predicted to be a binding site for the cellular transcription factor PHOX2A. In addition, phylogenetic analysis displayed a high prevalence of A lineage in HPV-16 LCR in this Southwest China population. This study may help understanding of the intrinsic geographical relatedness and the correlations between LCR mutations and the development of carcinogenic lesions in Southwest China population. And it provides useful data for the further study of the biological function of HPV-16 LCR variants.

In the present work, dry temperature profiles provided by the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) mission and the horizontal wind field provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis are combined for the first time to retrieve the magnitudes of gravity wave (GW) pseudomomentum flux (PMF). The vertical wave parameters, including Brunt−Väisälä frequencies, potential energy (Ep), and vertical wavelengths, are retrieved from RO temperature profiles. The intrinsic frequencies, which are retrieved from the horizontal wind field of ERA-Interim, are combined with the vertical wave parameters to derive the horizontal wavelengths and magnitudes of the PMF of GWs. The feasibility of this new strategy is validated first by comparing the distributions of GW parameters during June, July, and August (JJA) 2006 derived this way with those derived by previous studies. Then the seasonal and interannual variations of the distributions of GW PMF for three altitude ranges, 20−25 km, 25−30 km, and 30−35 km, over the globe during the seven years from June 2006 to May 2013 are presented. It is shown that the three altitude intervals share similar seasonal and interannual distribution patterns of GW PMF, while the magnitudes of GW PMF decrease with increased height and the hot spots of GW activity are the most discernable at the lowest altitude interval of 20−25 km. The maximums of PMF usually occur at latitudes around 60° in the winter hemispheres, where eastward winds prevail, and the second maximums exist over the subtropics of the summer hemispheres, where deep convection occurs. In addition, the influence of quasi-biennial oscillation (QBO) on both GW PMF and zonal winds is discernible over subtropical regions. The present work complements the GW PMF interannual variation patterns derived based on satellite observations by previous studies in terms of the altitude range, latitude coverage, and time period analyzed.

The objective of this study was to determine the in vitro antimicrobial activity of several organic acids and their derivatives against Gram-positive (G+) and Gram-negative (G−) bacteria. Butyric acid, valeric acid, monopropionin, monobutyrin, valerate glycerides, monolaurin, sodium formate, and ProPhorce—a mixture of sodium formate and formic acid (40:60 w/v)—were tested at 8 to 16 concentrations from 10 to 50,000 mg/L. The tested bacteria included G− bacteria (Escherichia coli, Salmonella enterica Typhimurium, and Campylobacter jejuni) and G+ bacteria (Enterococcus faecalis, Clostridium perfringens, Streptococcus pneumoniae, and Streptococcus suis). Antimicrobial activity was expressed as minimum inhibitory concentration (MIC) of tested compounds that prevented growth of tested bacteria in treated culture broth. The MICs of butyric acid, valeric acid, and ProPhorce varied among bacterial strains with the lowest MIC of 500−1000 mg/L on two strains of Campylobacter. Sodium formate at highest tested concentrations (20,000 mg/L) did not inhibit the growth of Escherichia coli, Salmonella Typhimurium, and Enterococcus faecalis, but sodium formate inhibited the growth of other tested bacteria with MIC values from 2000 to 18,800 mg/L. The MIC values of valerate glycerides, monolaurin, and monobutyrin ranged from 2500 to 15,000 mg/L in the majority of bacterial strains. Monopropionin did not inhibit the growth of all tested bacteria, with the exception that the MIC of monopropionin was 11,300 mg/L on Clostridia perfringens. Monolaurin strongly inhibited G+ bacteria, with the MIC value of 10 mg/L against Streptococcus pneumoniae. The MIC tests indicated that organic acids and their derivatives exhibit promising antimicrobial effects in vitro against G− and G+ bacteria that are resistant to antimicrobial drugs. The acid forms had stronger in vitro antimicrobial activities than ester forms, except that the medium chain fatty acid ester monolaurin exhibited strong inhibitory effects on G+ bacteria.

In this study, two ionospheric peak parameters (ICPs), NmF2 and hmF2, derived from the global navigation satellite system (GNSS) radio occultation (RO) ionospheric electron density profiles (EDPs) obtained by Feng-Yun 3C (FY-3C) mission are compared with those derived from the observations of the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) mission and the measurements from 24 digisonde stations distributed around the world during the year from 2014 to 2017. The FY-3C derived ICPs and the COSMIC-derived ICPs are provided by the National Satellite Meteorological Centre (NSMC) and the COSMIC Data Analysis and Archive Center (CDAAC), respectively. The correlation and bias analyses are carried out in the comparison under the collocation criterion with the time interval of 1 h and the space interval of 3° in latitude and 5° in longitude. When comparing the ICPs derived from the two RO missions, the difference in the azimuth of occultation planes (DAOPs) between the matched pairs is limited to be within 20°. The comparison results are analyzed for different solar activity periods, and solar elevation angle (SEA) is taken for the first time as a factor that represents the comprehensive impacts of latitude zones, seasons, and local time of the observations. The results are shown as follows: (1) Both the COSMIC RO-derived and the digisonde-observed ICPs are in good agreement with the FY-3C RO-derived ones. The correlation coefficient (CC) between the NmF2 and hmF2 derived by COSMIC RO and FY-3C RO is 0.965 and 0.916, respectively, while the correlation coefficient between the NmF2 and hmF2 derived by digisonde and FY-3C RO is 0.924 and 0.832, respectively. The quality of FY-3C RO-derived ICPs are reliable enough for further applications. (2) The CC of NmF2 is, in general, higher than that of hmF2 when comparing FY-3C RO with other observations, and the overall MAB and MRB of FY-3C RO-derived ICPs during the higher solar activity period are higher than the ones during the lower solar activity period. The difference between the two RO missions is much smaller than that one between FY-3C RO and digisonde. (3) For a certain solar activity period, the standard deviations of the absolute bias (SDAB) and the standard deviations of the relative bias (SDRB) of FY-3C RO-derived ICPs compared with digisonde-derived ones generally increases with the increase of SEA, while the SDAB and SDRB of FY-3C RO-derived ICPs both get the minimum values for the AOP interval near to 90°.

Red yeast rice (RYR) is made by fermenting the rice with Monascus. It is commonly used in food colorants, dyeing, and wine making in China and its neighboring countries. Nowadays RYR has two forms on the market: common RYR is used for food products, the other form is functional RYR for medicine. However, some researchers reported that commercial lovastatin (structure is consistent with monacolin K) is illegally added to common RYR to meet drug quality standards, so as to imitate functional RYR and sell the imitation at a higher price. Based on current detection methods, it is impossible to accurately distinguish whether functional RYR is adulterated. Therefore, it is especially important to find a way to authenticate functional RYR. In the current review, the advances in history, applications, components (especially monacolins, monacolins detection methods), quality standards, authentication methods and perspectives for the future study of RYR are systematically reviewed.

Given the great achievements of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission in providing huge amount of GPS radio occultation (RO) data for weather forecasting, climate research, and ionosphere monitoring, further Global Navigation Satellite System (GNSS) RO missions are being followingly planned. Higher spatial and also temporal sampling rates of RO observations, achievable with higher number of GNSS/receiver satellites or optimization of the Low Earth Orbit (LEO) constellation, are being studied by high number of researches. The objective of this study is to design GNSS RO missions which provide multi-GNSS RO events (ROEs) with the optimal performance over the globe. The navigation signals from GPS, GLONASS, BDS, Galileo, and QZSS are exploited and two constellation patterns, the 2D-lattice flower constellation (2D-LFC) and the 3D-lattice flower constellation (3D-LFC), are used to develop the LEO constellations. To be more specific, two evolutionary algorithms, including the genetic algorithm (GA) and the particle swarm optimization (PSO) algorithm, are used for searching the optimal constellation parameters. The fitness function of the evolutionary algorithms takes into account the spatio-temporal sampling rate. The optimal RO constellations are obtained for which consisting of 6–12 LEO satellites. The optimality of the LEO constellations is evaluated in terms of the number of global ROEs observed during 24 h and the coefficient value of variation (COV) representing the uniformity of the point-to-point distributions of ROEs. It is found that for a certain number of LEO satellites, the PSO algorithm generally performs better than the GA, and the optimal 2D-LFC generally outperforms the optimal 3D-LFC with respect to the uniformity of the spatial and temporal distributions of ROEs.

In this study, the relationship between gravity wave (GW) potential energy (Ep) and the tropopause height and temperature over the globe was investigated using COSMIC radio occultation (RO) dry temperature profiles during September 2006 to May 2013. The monthly means of GW Ep with a vertical resolution of 1 km and tropopause parameters were calculated for each 5° × 5° longitude-latitude grid. The correlation coefficients between Ep values at different altitudes and the tropopause height and temperature were calculated accordingly in each grid. It was found that at middle and high latitudes, GW Ep over the altitude range from lapse rate tropopause (LRT) to several km above had a significantly positive/negative correlation with LRT height (LRT-H)/ LRT temperature (LRT-T) and the peak correlation coefficients were determined over the altitudes of 10⁻14 km with distinct zonal distribution characteristics. While in the tropics, the distributions of the statistically significant correlation coefficients between GW Ep and LRT/cold point tropopause (CPT) parameters were dispersive and the peak correlation were are calculated over the altitudes of 14⁻38 km. At middle and high latitudes, the temporal variations of the monthly means and the monthly anomalies of the LRT parameters and GW Ep over the altitude of 13 km showed that LRT-H/LRT-T increases/decreases with the increase of Ep, which indicates that LRT was lifted and became cooler when GWs propagated from the troposphere to the stratosphere. In the tropical regions, statistically significant positive/negative correlations exist between GW Ep over the altitude of 17⁻19 km and LRT-H/LRT-T where deep convections occur and on the other hand, strong correlations exist between convections and the tropopause parameters in most seasons, which indicates that low and cold tropopause appears in deep convection regions. Thus, in the tropics, both deep convections and GWs excited accordingly have impacts on the tropopause structure.

AIM:To explore the correlation between the retinal nerve fiber layer (RNFL) thickness by using optical coherence tomography (OCT) and by histological measurements in normal adult rats and optic nerve transected rats.METHODS:The RNFL thickness of 36 rats was scanned in a circle 3.46mm far from the optic disc by OCT. The two experimental groups were the normal group (n=20 rats) and the optic nerve transected group (n=16 rats). The latter group included 4 groups (n=4/group) surviving for 1 day, 3, 5 and 7 days. Then the RNFL thickness of the same retina area was also measured by NF-200 immunohistochemical staining method. Linear regression was used to analyze the correlation between the data obtained from these two methods.RESULTS: The RNFL thickness of normal right eyes around optic disc by OCT was 72.35±5.71μm and that of the left eyes was 72.65±5.88μm (P=0.074). The RNFL thickness of the corresponding histological section by immunohistochemistry was 37.54±4.05μm (right eyes) and 37.38±4.23μm (left eyes) (P=0.059). There was a good correlation between the RNFL thickness measured by OCT and that measured by histology (R2=0.8131). After optic nerve transection, the trend of the RNFL thickness was thinner with the prolonged survival time. The correlation of the thickness detected by the above two methods was approximately (R2=0.8265). Value of the RNFL thickness in rats around optic disc measured by OCT was obviously higher than that measured by common histological measurement in normal adult rats and optic nerve transected rats.CONCLUSION: The RNFL thickness measured by OCT has a strong correlation with that measured by histological method. Through OCT scanning, we found that the thickness of RNFL gradually becomes thinner in a time-dependent manner.

Bisureido- and a bisthioureido-substituted dibenzobarrelene derivative were synthesized and the photoreactivity of two representative examples were studied. Direct irradiation of the ureido-substituted derivative induces a di-π-methane rearrangement to the corresponding dibenzosemibullvalene derivative, whereas the thioureido-substituted derivative is almost photoinert. Complexes of the latter derivative with chloride, carboxylates, or sulfonate anions, however, are efficiently transformed to the dibenzosemibullvalene product upon irradiation, presumably by suppressing the self-quenching of the thiourea units in the complex. The association of the ureido-substituted dibenzobarrelene derivative with (S)-mandelate and irradiation of this complex led to the formation of the dibenzosemibullvalene with moderate stereoselectivity (68:32 er). In contrast, the thioureido derivative showed no such effect upon complexation of chiral anions.

Dibenzobarrelene derivatives, that are annelated with a pyrrolinium unit [N,N-dialkyl-3,4-(9',10'-dihydro-9',10'-anthraceno-3-pyrrolinium) derivatives], undergo a photo-induced di-π-methane rearrangement upon triplet sensitization to give the corresponding cationic dibenzosemibullvalene derivatives [N,N-dialkyl-3,4-{8c,8e-(4b,8b-dihydrodibenzo[a,f]cyclopropa[cd]pentaleno)}pyrrolidinium derivatives]. Whereas the covalent attachment of a benzophenone functionality to the pyrrolinium nitrogen atom did not result in an internal triplet sensitization, the introduction of a benzophenone unit as part of the counter ion enables the di-π-methane rearrangement of the dibenzobarrelene derivative in the solid-state. Preliminary experiments indicate that a cationic pyrrolidinium-annelated dibenzosemibullvalene may act as phase-transfer catalyst in alkylation reactions.

Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and differentiation capacity, play an important role in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The recent research evidence suggests that alcohol increases the CSC population in cancers, which may underlie alcohol-induced tumor promotion. This review discusses the recent progress in the research of alcohol promotion of CSC and underlying cellular/molecular mechanisms. The review will further explore the therapeutic potential of CSC inhibition in treating alcohol-induced tumor promotion.

Animal growth curves can provide essential information for animal breeders to optimize feeding and management strategies. However, the genetic mechanism underlying the phenotypic differentiation between the inflection point and asymptotic stages of the growth curve is not well characterized. Here, we employed Liangshan pigs in stages of growth at the inflection point (under inflection point: UIP) and the two asymptotic stages (before the inflection point: BIP, after the inflection point: AIP) as models to survey global gene expression in the longissimus dorsi muscle using digital gene expression (DGE) tag profiling. We found Liangshan pigs reached maximum growth rate (UIP) at 163.6 days of age and a weight of 134.6 kg. The DGE libraries generated 117 million reads of 5.89 gigabases in length. 21,331, 20,996 and 20,139 expressed transcripts were identified BIP, UIP and AIP, respectively. Among them, we identified 757 differentially expressed genes (DEGs) between BIP and UIP, and 271 DEGs between AIP and UIP. An enrichment analysis of DEGs proved the immune system was strengthened in the AIP stage. Energy metabolism rate, global transcriptional activity and bone development intensity were highest UIP. Meat from Liangshan pigs had the highest intramuscular fat content and most favorable fatty acid composition in the AIP. Three hundred eighty (27.70%) specific expression genes were highly enriched in QTL regions for growth and meat quality traits. This study completed a comprehensive analysis of diverse genetic mechanisms underlying the inflection point and asymptotic stages of growth. Our findings will serve as an important resource in the understanding of animal growth and development in indigenous pig breeds.

Water bodies are major areas for methane release. Eutrophic water bodies may promote methane flux. The sediment-water interface is the major location for methane release, and studies on sediment-water interactions are necessary to regulate methane release in water. However, relevant studies on methane flux at the sediment-water interface are limited due to methodological difficulties. Using an innovative gas trapping device, this study investigated the seasonal characteristics and diel variation in summer methane flux from eutrophic water bodies and analyzed the correlations between temperature, dissolved oxygen (DO), different forms of nitrogen and the methane flux at different time scales. The results showed that methane flux in the eutrophic pond was high and had distinct seasonal variations and diel variations: the average value was 2.81 ± 0.19 mmol m−2 h−1 in summer, which was significantly greater than that in spring (0.62 ± 0.14 mmol m−2 h−1), autumn (0.63 ± 0.10 mmol m−2 h−1) (p < 0.01) and winter (approached zero). The diel characteristics of methane flux in summer exhibited a unimodal pattern of increase at night and decrease during the day. The correlation analysis showed that the sediment-water methane flux rate of the water body was significantly positively correlated with the temperature and NH4+ concentration and significantly negatively correlated with DO, NO3− and NO2− concentration. Meanwhile, among different time scales, the correlations between NO3−/NH4+ concentration and methane flux were the highest at the diel scale in summer (R2 = 0.68, 0.87 respectively) when the temperature and DO vibration was low and the relationship between temperature/DO and methane flux was poor (R2 = 0.45, 0.87 respectively). This study considered that higher NH4+-N and lower NO3−-N/NO2−-N content in eutrophic water could have an effect on the high methane flux in summer as well as the low dissolved oxygen content.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved neurotrophic factor which exhibited neuroprotective properties. Recent studies suggested that MANF may play a role in the neural development of Drosophila and zebra fishes. In this study, we investigated the spatiotemporal expression of MANF in the brain of postnatal and adult rats. MANF expression appeared wide spread and mainly localized in neurons. In the cerebral cortex, neurons in layer IV and VI displayed particularly strong MANF immunoreactivity. In the hippocampus, intensive MANF expression was observed throughout the subfields of Cornu Amonis (CA1, CA2, and CA3) and the granular layer of the dentate gyrus (DG). In the substantia nigra, high MANF expression was shown in the substantia nigra pars compacta (SNpc). In the thalamus, the anterodorsal thalamic nucleus (ADTN) exhibited the highest MANF immunoreactivity. In the hypothalamus, intensive MANF immunoreactivity was shown in the supraoptic nucleus (SON) and tuberomammillary nucleus (TMN). In the cerebellum, MANF was localized in the external germinal layer (EGL), Purkinje cell layer (PCL), internal granule layer (IGL) and the deep cerebellar nuclei (DCN). We examined the developmental expression of MANF on postnatal day (PD) 3, 5, 7, 9, 15, 21, 30 and adulthood. In general, the levels of MANF were high in the early PDs (PD3 and PD5), and declined gradually as the brain matured; MANF expression in the adult brain was the lowest among all time points examined. However, in some structures, such as PCL, IGL, SON, TMN and locus coeruleus (LC), high expression of MANF sustained throughout the postnatal period and persisted into adulthood. Our results indicated that MANF was developmentally regulated and may play a role in the maturation of the central nervous system (CNS).

Graphene nanoplatelet (GNP)–epoxy composites were fabricated for the investigation of the dielectric permittivity and microwave absorption in a frequency range from 8 to 20 GHz. The intrinsically conductive GNP particles and polarized interfacial centers in the composites contribute to the microwave absorption. A minimum reflection loss of −14.5 dB at 18.9 GHz is observed for the GNP–epoxy composites with 15 wt. % GNP loading, which is mainly attributed to electric conductivity and the charge multipoles at the polarized interfaces in the GNP–epoxy composites.

KIF20A (Kinesin-like family member 20A), also called mitotic kinesin-like proteins 2 (MKLP2), is a mammalian mitotic kinesin-like motor protein of the Kinesin superfamily proteins (KIFs), which was originally involved in Golgi apparatus dynamics and thought to essential for cell cycle regulation during successful cytokinesis. In the present study, we investigated whether KIF20A has roles on porcine oocyte meiotic maturation and subsequent early embryo development. By immunofluorescence staining, KIF20A was found to exhibit a dynamic localization pattern during meiosis. KIF20A was restricted to centromeres after germinal vesicle breakdown (GVBD), transferred to the midbody at telophase I (TI), and again associated with centromeres at metaphase II (MII). Inhibition of endogenous KIF20A via a specific inhibitor, Paprotrain, resulted in failure of polar body extrusion. Further cell cycle analysis showed that the percentage of oocytes that arrested at early metaphase I (MI) stage increased after KIF20A activity inhibition; however, the proportion of oocytes at anaphase/telophase I (ATI) and MII stages decreased significantly. Our results also showed that KIF20A inhibition did not affect spindle morphology. In addition, KIF20A was localized at the nucleus of early embryos, and KIF20A inhibition resulted in failure of early parthenogenetic embryo development. These results demonstrated that KIF20A is critical for porcine oocyte meiotic maturation and subsequent early embryo development.

Selective estrogen receptor modulators (SERMs) are effective therapeutics that preserve favorable actions of estrogens on bone and act as antiestrogens in breast tissue, decreasing the risk of vertebral fractures and breast cancer, but their potential in neuroprotective and procognitive therapy is limited by: 1) an increased lifetime risk of thrombotic events; and 2) an attenuated response to estrogens with age, sometimes linked to endothelial nitric oxide synthase (eNOS) dysfunction. Herein, three 3(rd) generation SERMs with similar high affinity for estrogen receptors (ERα, ERβ) were studied: desmethylarzoxifene (DMA), FDMA, and a novel NO-donating SERM (NO-DMA). Neuroprotection was studied in primary rat neurons exposed to oxygen glucose deprivation; reversal of cholinergic cognitive deficit was studied in mice in a behavioral model of memory; long term potentiation (LTP), underlying cognition, was measured in hippocampal slices from older 3×Tg Alzheimer's transgenic mice; vasodilation was measured in rat aortic strips; and anticoagulant activity was compared. Pharmacologic blockade of GPR30 and NOS; denudation of endothelium; measurement of NO; and genetic knockout of eNOS were used to probe mechanism. Comparison of the three chemical probes indicates key roles for GPR30 and eNOS in mediating therapeutic activity. Procognitive, vasodilator and anticoagulant activities of DMA were found to be eNOS dependent, while neuroprotection and restoration of LTP were both shown to be dependent upon GPR30, a G-protein coupled receptor mediating estrogenic function. Finally, the observation that an NO-SERM shows enhanced vasodilation and anticoagulant activity, while retaining the positive attributes of SERMs even in the presence of NOS dysfunction, indicates a potential therapeutic approach without the increased risk of thrombotic events.

3,3'-Diindolylmethane (DIM), one of the active products derived from Brassica plants, is a promising antitumor agent. The present study indicated that DIM significantly induced apoptosis in U937 human leukemia cells in dose- and time-dependent manners. These events were also noted in other human leukemia cells (Jurkat and HL-60) and primary human leukemia cells (AML) but not in normal bone marrow mononuclear cells. We also found that DIM-induced lethality is associated with caspases activation, myeloid cell leukemia-1 (Mcl-1) down-regulation, p21(cip1/waf1) up-regulation, and Akt inactivation accompanied by c-jun NH2-terminal kinase (JNK) activation. Enforced activation of Akt by a constitutively active Akt construct prevented DIM-mediated caspase activation, Mcl-1 down-regulation, JNK activation, and apoptosis. Conversely, DIM lethality was potentiated by the PI3K inhibitor LY294002. Interruption of the JNK pathway by pharmacologic or genetic approaches attenuated DIM-induced caspases activation, Mcl-1 down-regulation, and apoptosis. Lastly, DIM inhibits tumor growth of mouse U937 xenograft, which was related to induction of apoptosis and inactivation of Akt, as well as activation of JNK. Collectively, these findings suggest that DIM induces apoptosis in human leukemia cell lines and primary human leukemia cells, and exhibits antileukemic activity in vivo through Akt inactivation and JNK activation.

Angiogenesis is a crucial step in the growth and metastasis of cancers, since it enables the growing tumor to receive oxygen and nutrients. Cancer prevention using natural products has become an integral part of cancer control. We studied the antiangiogenic activity of quercetin using ex vivo, in vivo and in vitro models. Rat aortic ring assay showed that quercetin at non-toxic concentrations significantly inhibited microvessel sprouting and exhibited a significant inhibition in the proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Most importantly, quercetin treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Western blot analysis showed that quercetin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, mTOR, and ribosomal protein S6 kinase in HUVECs. Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis. Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, mTOR and P70S6K expressions. Collectively the findings in the present study suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy.

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9. Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 in HUVECs. Proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α level were significantly reduced by the treatment of luteolin in PC-3 cells. Luteolin (10 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that luteolin inhibited tumorigenesis by targeting angiogenesis. CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin. Moreover, luteolin reduced cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 expressions. Taken together, our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.

Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is an interferon-induced protein kinase that plays a central role in the anti-viral process. Due to its pro-apoptotic and anti-proliferative action, there is an increased interest in PKR modulation as an anti-tumor strategy. PKR is overexpressed in breast cancer cells; however, the role of PKR in breast cancer cells is unclear. The expression/activity of PKR appears inversely related to the aggressiveness of breast cancer cells. The current study investigated the role of PKR in the motility/migration of breast cancer cells. The activation of PKR by a synthesized dsRNA (PIC) significantly decreased the motility of several breast cancer cell lines (BT474, MDA-MB231 and SKBR3). PIC inhibited cell migration and blocked cell membrane ruffling without affecting cell viability. PIC also induced the reorganization of the actin cytoskeleton and impaired the formation of lamellipodia. These effects of PIC were reversed by the pretreatment of a selective PKR inhibitor. PIC also activated p38 mitogen-activated protein kinase (MAPK) and its downstream MAPK-activated protein kinase 2 (MK2). PIC-induced activation of p38 MAPK and MK2 was attenuated by the PKR inhibitor and the PKR siRNA, but a selective p38 MAPK inhibitor (SB203580) or other MAPK inhibitors did not affect PKR activity, indicating that PKR is upstream of p38 MAPK/MK2. Cofilin is an actin severing protein and regulates membrane ruffling, lamellipodia formation and cell migration. PIC inhibited cofilin activity by enhancing its phosphorylation at Ser3. PIC activated LIM kinase 1 (LIMK1), an upstream kinase of cofilin in a p38 MAPK-dependent manner. We concluded that the activation of PKR suppressed cell motility by regulating the p38 MAPK/MK2/LIMK/cofilin pathway.

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47(phox) and p67(phox), the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47(phox) and p67(phox), which were prerequisites for NOX assembly and activation. Knocking down p47(phox) with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanol-mediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation. Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation. These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons.

Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar) disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD) are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3) which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.