Search

Glial cell-line derived neurotrophic factor (GDNF) is a powerful astroglioma (AG) proliferation and migration factor that is highly expressed in AG cells derived from astrocytes. However, it is still unclear whether high levels of GDNF promote AG occurrence or if they are secondary to AG formation. We previously reported that high concentrations of GDNF (200 and 500 ng/mL) can inhibit DNA damage-induced rat primary astrocytes (RA) apoptosis, suggesting that high concentrations of GDNF may be involved in the malignant transformation of astrocytes to AG cells. Here we show that 200 ng/mL GDNF significantly increased the proliferation and migration ability of RA cells and human primary astrocytes (HA). This treatment also induced RA cells to highly express Pgf, Itgb2, Ibsp, Loxl2, Lif, Cxcl10, Serpine1, and other genes that enhance AG proliferation and migration. LOXL2 is an important AG occurrence and development promotion factor and was highly expressed in AG tissues and cells. High concentrations of GDNF promote LOXL2 expression and secretion in RA cells through GDNF family receptor alpha-1(GFRα1)/rearranged during transfection proto-oncogene (RET)/mitogen-activated protein kinase (MAPK)/phosphorylated cyclic AMP response element binding protein (pCREB) signaling. GDNF-induced LOXL2 significantly promotes RA and HA cell proliferation and migration, and increases the expression of Ccl2, Gbp5, MMP11, TNN, and other genes that regulate the extracellular microenvironment in RA cells. Our results demonstrate that high concentrations of GDNF activate LOXL2 expression and secretion via the GFRα1/RET/MAPK/pCREB signal axis, which leads to remodeling of the astrocyte extracellular microenvironment through molecules such as Ccl2, Gbp5, MMP11, TNN. This ultimately results in abnormal astrocyte proliferation and migration. Collectively, these findings suggest that high GDNF concentrations may promote the malignant transformation of astrocytes to AG cells.

Background Ammonium (NH4+) is a key nitrogen source supporting plant growth and development. Proteins in the ammonium transporter (AMT) family mediate the movement of NH4+ across the cell membrane. Although several studies have examined AMT genes in various plant species, few studies of the AMT gene family have been conducted in chili pepper. Results Here, a total of eight AMT genes were identified in chili pepper, and their exon/intron structures, phylogenetic relationships, and expression patterns in response to arbuscular mycorrhizal (AM) colonization were explored. Synteny analyses among chili pepper, tomato, eggplant, soybean, and Medicago revealed that the CaAMT2;1, CaAMT2.4, and CaAMT3;1 have undergone an expansion prior to the divergence of Solanaceae and Leguminosae. The expression of six AMT2 genes was either up-regulated or down-regulated in response to AM colonization. The expression of CaAMT2;1/2;2/2;3 and SlAMT2;1/2;2/2;3 was significantly up-regulated in AM fungi-inoculated roots. A 1,112-bp CaAMT2;1 promoter fragment and a 1,400-bp CaAMT2;2 promoter fragment drove the expression of the β-glucuronidase gene in the cortex of AM roots. Evaluation of AM colonization under different NH4+ concentrations revealed that a sufficient, but not excessive, supply of NH4+ promotes the growth of chili pepper and the colonization of AM. Furthermore, we demonstrated that CaAMT2;2 overexpression could mediate NH4+ uptake in tomato plants. Conclusion In sum, our results provide new insights into the evolutionary relationships and functional divergence of chili pepper AMT genes. We also identified putative AMT genes expressed in AM symbiotic roots.

Physico-mechanical properties of shale are important parameters in evaluating the stability of potential wellbore and the design of hydraulic fracturing, which are primarily affected by their non-uniform spatial distribution of the microscopic physical–mechanical properties at particle scale. A series of constant strain rate experiments and stress-cycling experiments on shale specimens with different bedding dip angles were conducted to have a comprehensive understanding of the effect of the non-uniform distribution of microscopic failure stress on macroscopic physico-mechanical properties. According to the experimental results and Weibull distribution, we find that bedding dip angle and the dynamic load applying type affect the spatial distributions of microscopic failure stress. The values of crack damage stress (σcd), σcd/σucs (peak stress), εcd (strain at crack damage stress), Poissons' ratio (ν), elastic strain energy (Ue) and dissipated energy (Uirr) of the specimens with more uniform distribution of microscopic failure stress are overall higher, while εucs (peak strain)/εcd and elastic modulus (E) are lower. The dynamic load enables the spatial distributions of microscopic failure stress trend to be more homogeneous prior to the final failure with the increment of σcd/σucs, ν, Ue and Uirr and the decrement of E.

Background Although cholesterol metabolism is a common pathway for the development of antitumor drugs, there are no specific targets and drugs for clinical use. Here, based on our previous study of sterol O-acyltransferase 1 (SOAT1) in hepatocelluar carcinoma, we sought to screen an effective targeted drug for precise treatment of hepatocelluar carcinoma and, from the perspective of cholesterol metabolism, clarify the relationship between cholesterol regulation and tumorigenesis and development. Methods In this study, we developed a virtual screening integrated affinity screening technology for target protein drug screening. A series of in vitro and in vivo experiments were used for drug activity verification. Multi-omics analysis and flow cytometry analysis were used to explore antitumor mechanisms. Comparative analysis of proteome and transcriptome combined with survival follow-up information of patients reveals the clinical therapeutic potential of screened drugs. Results We screened three compounds, nilotinib, ABT-737, and evacetrapib, that exhibited optimal binding with SOAT1. In particular, nilotinib displayed a high affinity for SOAT1 protein and significantly inhibited tumor activity both in vitro and in vivo. Multi-omics analysis and flow cytometry analysis indicated that SOAT1-targeting compounds reprogrammed the cholesterol metabolism in tumors and enhanced CD8+ T cells and neutrophils to suppress tumor growth. Conclusions Taken together, we reported several high-affinity SOAT1 ligands and demonstrated their clinical potential in the precision therapy of liver cancer, and also reveal the potential antitumor mechanism of SOAT1-targeting compounds. Graphical Abstract

Cadmium exposure may increase the risk of osteoporosis. However, there is no quick method to get bone mineral density (BMD) unless dual-energy X-ray absorptiometry (DXA) examinations were performed. In the present study, we aimed to identify associated factors to osteoporosis and fracture in a Chinese female population with cadmium exposure and develop nomograms to predict the risk. A total of 488 women was included in this study. Cadmium in blood (BCd) and urine (UCd) were determined as exposure biomarkers. BMD was determined using single-photon absorptiometry. Urinary N-acetyl-β-d-glucosaminidase (UNAG) and urinary albumin (UALB) were determined as renal function biomarkers. Osteoporosis was defined if T-score

Polymer/graphene composite films with a nacre-like layered structure have been extensively researched. However, most composites have been prepared using a small amount of graphene up to now, which extremely restricts the mechanical and electrical properties. Herein, a series of polymers (HEC, HPMC, and PVA)/graphene layered composites with high-content graphene (from 45 to 75%) are prepared by simple solution evaporation and then reduction method. The mechanical and electrical properties of these composites are studied. Mechanical results show with the increase of graphene oxide (GO) content, the tensile strength increases, and later decreases. Electrical performance indicates that the electrical conductivity of HPMC/rGO is greater than both HEC/rGO and PVA/rGO. Considering mechanical and electrical performance, HPMC/rGO-65 with 65% graphene content is better than others, and its tensile strength and the conductivity are 32.08 MPa and 0.63 S/m, respectively. This work provides a new strategy for developing biomimetic nacre-like composites with high graphene content, which could improve the comprehensive properties of polymer/graphene.

Changes in soil organic carbon (SOC) stock have major impacts on global terrestrial carbon cycling. However, their responses to land use conversions are poorly characterized for karst areas with extremely fragile geology and intensive human disturbance. To investigate the effects of soil type and land use on SOC stock in a typical karst region of southwestern China, 0–15 cm topsoil samples were randomly collected in 2015. Furthermore, in the same locations as the sites in 1983, 0–100 cm stratified profile soil samples (0–10, 10–20, 20–30, 30–50, 50–70, and 70–100 cm) were collected to evaluate the changes in SOC stock as affected by land use conversions from 1983 to 2015. The current SOC stock in 0–15 cm differed significantly between Calcisols and Ferralsols, and was highest in the secondary forest, followed by shrubland, grassland, plantation forest, and cropland. Changes in the stratified SOC stock (both recalculated to 0–20, 20–40, 40–60, 60–80, and 80–100 cm intervals in 1983 and 2015) varied among different land use conversions. Average stratified SOC stock decreased after forest degradation and reclamation, except in 80–100 cm. After reforestation, it had decreases in 0–20 and 20–40 cm, whereas it increased in subsoil (40–60, 60–80, and 80–100 cm). However, compared with the cropland in which soil was exposed to continuous conventional tillage, average stratified SOC stock increased in all soil layers after reforestation. The increases in SOC stock after reforestation and re-cultivation (short-term reuse in abandoned croplands) indicated the positive role of agricultural abandonment in increasing terrestrial SOC stock.

In this paper, we investigate the adequate check of the parametric Tobit model. A Cramer–Von Mises type test statistic is constructed, and its asymptotic properties under the null and alternative hypotheses are rigorously studied. The method is effective for the adequacy check of parametric regression models with a scalar or multivariate covariate. Furthermore, it avoids the nonparametric smoothing of the regression function and the choice of the smoothing parameter. Simulation studies are conducted to compare the performance of the proposed test procedure and the existing methods in the literature. A real data set of income is analyzed by applying the proposed method.

Background Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. Materials and methods 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients’ demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. Results The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P P ) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16–268.46, P = 0.02 ).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs. Conclusions HDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs.

Shale formations suffer dynamic loading and unloading stresses during hydraulic fracturing processes that cause cracks to open and shear-slip to develop, while simultaneously producing microseismicity. Incremental cyclic loading tests were conducted on shale specimens using various stress levels and measured via real-time acoustic emission (AE) monitoring at the laboratory scale because AE parameters are useful in understanding heterogeneous material damage behaviour. Parallel (θ = 0°) and vertically (θ = 90°) cored shale specimens were cyclically loaded from lower stress levels of 0.3 and 0.47 and higher stress levels of 0.8 and 0.84, respectively, to analyze the effects of the bedding plane and loading level on the fracture process. Based on temporal variation of the AE amplitude in response to the stress paths, the longer AE activity quiet period noted during the loading stage in each cycle for 90° shale specimens shows that the Kaiser effect is more pronounced for vertically cored specimens than for parallel cored specimens. This phenomenon is also evidenced by the smaller load ratios observed with θ = 0° (as compared to θ = 90°) specimens. This indicates easier crack generation at lower stresses and is independent of the loading path. Meanwhile, high calm ratios indicate the initiation of numerous cracks during the unloading stage. Therefore, the load ratio can be combined with the calm ratio to evaluate the difficulty of crack generation in shale. In addition, the AE amplitude distribution shows that the proportion of large cracks increases when shale specimens are loaded from higher stress levels. Moreover, the average frequency and RA value (obtained from the rise time and amplitude) were used to characterize damage mechanisms. A decreasing average frequency and increasing RA value for parallel cored specimens from lower stress levels or small average frequency and large RA value from higher stress levels both indicate the dominant shear type that contributes to the failure process and causes splitting along the bedding plane. The higher average frequency and lower RA values noted for vertically cored specimens imply that tensile modes control the failure process and cause finally side-step main fracture plane across the bedding plane.

Punctate white matter lesions (PWML) are common in preterm neonates and have also been reported in the full term. While most studies focus on white matter abnormalities, gray matter (GM) alterations are generally ignored due to the lack of abnormalities on conventional MRI. This study aims to investigate whether magnetic resonance spectroscopy is a sensitive and practical method to detect occult alterations of deep GM nuclei in these neonates. Neonates with PWML and controls with no MRI abnormalities were retrospectively studied. Apparent diffusion coefficient values and metabolic ratios (Cho/Cr, NAA/Cho, and NAA/Cr) in the lenticular nucleus and the thalamus were compared between the PWML and control groups. Forty-two neonates with PWML (grades I, II, and III contained 14, 21, and 7 subjects, respectively) and 50 controls were enrolled. Apparent diffusion coefficient values in the lenticular nucleus and the thalamus were not significantly different between the PWML and the control groups. The NAA/Cho ratio was significantly lower in the PWML group than in the control group in both regions, whereas a lower NAA/Cr ratio was only observed in the thalamus. Significantly lower ratios of NAA/Cho in both regions and NAA/Cr in the thalamus were detected in the grade II and III subgroup, whereas the thalamic NAA/Cho ratio was decreased in the grade I group compared with controls. Magnetic resonance spectroscopy is a sensitive method for detecting the occult deep GM abnormalities for the study cohort of neonates with PWML when compared with subjects without PWML.

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disease caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene that often results in cognitive impairment, psychiatric disorders, motor dysfunction and seizure. We report familial cases of a novel CSF1R mutation causing HDLS similar to hydrocephalus. The patients initially presented with a gait disturbance and then developed progressive cognitive decline, urinary incontinence, epileptic seizures and became bedridden as the disease progressed. A brain magnetic resonance imaging (MRI) scan revealed striking ventricular enlargement and diffuse brain atrophy with frontotemporal predominance, which was later accompanied by white matter changes. Genetic testing in this family showed a novel c.2552T>C (p.L851P) mutation in exon 19 of the CSF1R gene. However, three gene carriers in the family remained clinically asymptomatic. Because of its heterogeneous clinical phenotypes, HDLS patients are often misdiagnosed with other diseases. This is the first genetically proven HDLS case resembling hydrocephalus, and the clinical symptoms of HDLS may be related to the specific genetic mutation.

In this study, a three dimensional (3D) MoS2/β-Bi2O3 heterostructure with high-performance for photocatalytic removal of pollutants was constructed by a simple deposition of the MoS2 quantum dots on the surface of porous β-Bi2O3 spheres. Compared with pure β-Bi2O3 microspheres, the 1.0% MoS2/β-Bi2O3 composite exhibited excellent photocatalytic activity in the degradation of Bisphenol A (BPA) in aqueous solution and oxidative removal of gaseous NO under visible light irradiation, and the removal efficiency reached 94.0% and 41.4% for BPA and NO within 30 min, respectively. The enhanced photocatalytic activity is attributed to the formation heterojunction between MoS2 quantum dots and β-Bi2O3, which facilitates the separation and transfer efficiency of photogenerated electron–hole pairs, boosts catalytic active sites and hinders an electron–hole recombination rate. The results of trapping experiments indicates that both of O2−∙ and h+ are the reactive species for BPA degradation. The recyclability test confirms that the 1.0% MoS2/β-Bi2O3 composite photocatalyst has a superior stability during recycling cycle. This work demonstrates that a unique 3D photocatalyst system can provides a new perspective and opens up new opportunities on the design of efficient composite photocatalysts.

This study aims to provide a screening scoring method by assessing the age-related change of subcortical white matter (WM) myelination via T2-weighted imaging (T2WI). This study retrospectively recruited 109 children aged 6–48 months without abnormalities on MRI. Based on Parazzini’s study, we developed a modified T2WI-based method to assess subcortical WM myelination (frontal, temporal, parietal, occipital lobes, and insula) by scoring WM’s signal changes. Inter- and intra-observer agreements were evaluated by Bland-Altman plot. Age-related changes of myelination score were explored by locally weighted scatterplot smoothing (LOESS), linear regression, and Spearman correlation coefficients (r). Relationships between diffusion tensor imaging (DTI) metrics and total myelination score were investigated to further validate practicability of the scoring method by tract-based spatial statistics (TBSS). This method showed good intra-observer (mean difference = 0.18, SD = 0.95) and inter-observer agreements (mean difference = − 0.06, SD = 1.01). The LOESS and linear regression results indicated that myelination proceeded in two phases: a period of rapid growth (6–20 months; slope = 0.561) and one of slower growth (21–48 months; slope = 0.097). Significant correlations between myelination score and age were observed in whole subcortical WM (r = 0.945; P

A correlation study between the fracability and brittleness of shale gas reservoir is crucial for optimize reservoir reconstruction and enhance shale gas recovery. To investigate the relationship between fracability and brittleness of shale, a series of uniaxial compression tests of Silurian Longmaxi shale samples were carried out using a novel setup that combines X-ray micro-computed tomography with a uniaxial loading apparatus. Based on the CT images obtained from the test, fractal dimension of crack distribution that regarded as an effective index describing the fracability of shale was estimated, and the Weibull shape parameter that deemed as a reliable index to describe the brittleness of shale was calculated. The ratio of fractal dimension and Weibull shape parameter was close to a constant value of 2. To reveal the relationship between the fractal dimension and Weibull shape parameter, the quantitative relationship between the fractal dimension of the crack distribution and the Weibull shape parameter of the shale under tensile and compressive stress conditions was established by coupling the fracture mechanics and Weibull’s weakest-link theory, which validated that the shale fracability was directly proportional to its brittleness. The applicable range of the quantitative relationship showed that the proportional relationship only held for a low-brittleness shale. These results are significant for the fracturing and recovery of shale-gas reservoirs.

Endonuclease G (ENDOG), a mitochondrial nuclease, is known to participate in many cellular processes, including apoptosis and paternal mitochondrial elimination, while its role in autophagy remains unclear. Here, we report that ENDOG released from mitochondria promotes autophagy during starvation, which we find to be evolutionally conserved across species by performing experiments in human cell lines, mice, Drosophila and C. elegans. Under starvation, Glycogen synthase kinase 3 beta-mediated phosphorylation of ENDOG at Thr-128 and Ser-288 enhances its interaction with 14-3-3γ, which leads to the release of Tuberin (TSC2) and Phosphatidylinositol 3-kinase catalytic subunit type 3 (Vps34) from 14-3-3γ, followed by mTOR pathway suppression and autophagy initiation. Alternatively, ENDOG activates DNA damage response and triggers autophagy through its endonuclease activity. Our results demonstrate that ENDOG is a crucial regulator of autophagy, manifested by phosphorylation-mediated interaction with 14-3-3γ, and its endonuclease activity-mediated DNA damage response., The role of Endonuclease G in autophagy remains unclear. Here the authors report that ENDOG is released from mitochondria during starvation and promotes autophagy by suppressing mTOR signaling and activating DNA damage response.

In the geodetic community, an adjustment framework is established by the four components of model choice, parameter estimation, variance component estimation (VCE), and quality control. For linear ill-posed models, the parameter estimation and VCE have been extensively investigated. However, at least to the best of our knowledge, nothing is known about the quality control of hypothesis testing in ill-posed models although it is indispensable and rather important. In this paper, we extend the theory of hypothesis testing to ill-posed models. As the Tikhonov regularization is typically applied to stabilize the solution of ill-posed models, the solution and its associated residuals are biased. We first derive the statistics of overall-test, w-test and minimal detectable bias for an ill-posed model. Due to the bias influence, both overall-test and w-test statistics do not follow the distributions as those used in well-posed models. Then, we develop the bias-corrected statistics. As a result, the bias-corrected w-test statistic can sufficiently be approximated by a standard normal distribution; while the bias-corrected overall-test statistic can be approximated by two non-central chi-square distributions, respectively. Finally, some numerical experiments with a Fredholm first kind integral equation are carried out to demonstrate the performance of our designed hypothesis testing statistics in an ill-posed model.

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.

Background Brucellosis remains one of the most common zoonotic diseases globally, with more than half million human cases reported annually. Brucellosis is an emerging and re-emerging disease in China since the 1990s. An infectious reservoir constituted by domestic animals with brucellosis, especially ovine and caprine herds, poses a significant threat to public health. The seroprevalence of brucellosis in sheep and goat flocks in a national context is unavailable so far. Therefore, we conducted this systematic review and meta-analysis to assess the overall status of brucellosis in sheep and goats in China in almost two decades. Results The pooled prevalence of brucellosis in ovine and caprine flocks in China increased in 2000–2009 (1.00%; 95% CI, 0.70–1.30) to 2010–2018 (3.20%; 95% CI, 2.70–3.60). The seroprevalence of brucellosis in sheep and goat flocks was higher in Eastern China, with 7.00% of positive rate, than that in any other region, especially Shandong province (18.70%). Brucellosis is highly endemic in some local regions. The high prevalence of brucellosis in agricultural regions is suggestive of a shift of geographic distribution. The pooled prevalence of brucellosis is higher in goat flocks than in sheep flocks in China. Conclusions The overall data in this meta-analysis demands comprehensive intervention measures and further surveillance to facilitate the control of brucellosis in livestock. Further studies aimed at evaluating the risk factors associated with spreads of brucellosis in domestic animals unaddressed so far, and sufficient epidemiological data is important to the exploration and understanding of the prevalent status of brucellosis throughout the country and to disease control. Electronic supplementary material The online version of this article (10.1186/s12917-018-1715-6) contains supplementary material, which is available to authorized users.

Applying the statistical damage theory based on the Weibull distribution to describe rock deformation and failure processes is an important development in rock mechanics. The shape parameter of the Weibull distribution, m, determines the basic shape of the distribution curve; additionally, it also represents a physical characteristic which can be applied when constructing rock constitutive models. To study the evolution of m during rock failure when applying the Weibull distribution to rock mechanics, uniaxial cyclic loading tests of shale specimens were conducted and previous rock mechanics experiments under different temperatures and loading rates were reviewed. The results indicate that m varied with the accumulation of damage but was almost constant between the volume expansion point and the peak strength point of each specimen. Combined with previous studies about the accelerated failure behavior of rocks, we conclude that between the volume expansion point and the peak strength point, the mechanical behavior of the rock fracture process did not change significantly. Based on the characteristics of m at different damage stages during the rock failure process, ranges of m values at different damage stages are proposed. The conclusions reached in this study may be used as an important reference for theoretical research on rock mechanics.

It is clear that evaluating the fracturing effect with laboratory tests can shed some light on designing fracturing programs for shale gas exploitation. To evaluate the fracturing effect quantitatively, a series of uniaxial cyclic loading tests on shale were conducted. Based on the experimental results, a damage variable derived from the total axial strains of the loading–unloading cycles was established and introduced into a damage evolution equation to analyze damage evolution in the shale. In the end, a new index for evaluating the fracturing effect, $$C_{AN} '$$, was proposed. The results show that $$C_{AN} '$$ has a positive correlation with fracture complexity and can be regarded as an effective index to evaluate fracture networks in shale using laboratory tests. In addition, this study demonstrates that the fracturing effect is also related to the angle between the direction in which the load is applied and the shale’s bedding plane. This can provide a useful reference for shale gas exploitation.

This paper is based on rough set theory and neural networks, and mainly introduces the previous researchers how to use rough set theory, which has the superior ability to rule out redundant, and neural networks, which has the self-organizing and self-learning ability to complement each other's advantages, in order to obtain rough neural networks with better performance. This paper also details the possibility of the integration of these two theories and the current mainstream fusion method and then takes two more mainstream previous neural networks, back-propagation neural networks and radial basis function neural networks, as an example to integrate with rough set theory. This example describes the fusion method, fusion performance, and its corresponding learning algorithm after fusion in detail.

Capsaicin has multiple pharmacological activities including antioxidant, anticancer, and anti-inflammatory activities. However, its clinical application is limited due to its poor aqueous solubility, gastric irritation, and low oral bioavailability. This research was aimed at preparing sustained-release matrix pellets of capsaicin to enhance its oral bioavailability. The pellets comprised of a core of solid-dispersed capsaicin mixed with microcrystalline cellulose (MCC) and hydroxypropyl cellulose (HPMC) and subsequently coating with ethyl cellulose (EC) were obtained by using the technology of extrusion/spheronization. The physicochemical properties of the pellets were evaluated through scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). Besides, the in vitro release, in vivo absorption, and in vitro-in vivo correlation were also assessed. More importantly, the relative bioavailability of the sustained-release matrix pellets was studied in fasted rabbits after oral administration using free capsaicin and solid dispersion as references. The oral bioavailability of the matrix pellets and sustained-release matrix pellets of capsaicin was improved approximately 1.98-fold and 5.34-fold, respectively, compared with the free capsaicin. A good level A IVIVC (in vitro-in vivo correlation) was established between the in vitro dissolution and the in vivo absorption of sustained-release matrix pellets. All the results affirmed the remarkable improvement in the oral bioavailability of capsaicin owing to the successful preparation of its sustained-release matrix pellets.

Pollen tube growth in styles was strongly inhibited by temperature above 35 °C, and the yield of cotton decreased because of the adverse effect of high temperatures during square development. High-temperature stress during flowering influences the square development of upland cotton (Gossypium hirsutum L.) and cotton yield. Although it is well known that square development is sensitive to high temperature, high-temperature sensitive stages of square development and the effects of high temperature on pollen tube growth in the styles are unknown. The effect of high temperature on anther development corresponding to pollen vigor is unknown during anther development. The objectives of this study were to identify the stages of square development that are sensitive to high temperatures (37/30 and 40/34 °C), to determine whether the abnormal development of squares influenced by high temperature is responsible for the variation in the in vitro germination percent of pollen grains at anthesis, to identify the effect of high temperature on pollen germination in the styles, and to determine pollen thermotolerance heterosis. Our results show that the stages from the sporogenous cell to tetrad stage (square length

This paper investigated the theoretical relationship between the axial strain thresholds at the volumetric strain reversal point (e 1cd) and the strain threshold at the peak stress (e 1ucs) during a uniaxial compression test. Firstly, we used renormalization group theory with the stress transfer mechanism to reveal the essence of the phase transition phenomenon at the axial strain threshold (e 1cd). Then, we constructed mathematical expressions for e 1ucs and e 1cd, respectively. Finally, a theoretical expression for the normalized quantity e 1ucs/e 1cd was deduced. Results indicate that the theoretical solution of e 1ucs/e 1cd is a function of the shape parameter m. We determined m values in the granitic gneiss experiments presented in Part I of this paper, and then compared the experimental results with theoretical solutions for e 1ucs/e 1cd. It was observed that, for a given m, the experimental results were approximately consistent with the theoretical values for the two- and three-dimensional renormalization group models. This indicates that the two- and three-dimensional renormalization group models of rock fracture processes can be used to describe the mechanical behavior of laboratory-scale rock samples. Therefore, this study has thrown some light on failure prediction for laboratory-scale rock samples. Furthermore, the results show that e 1ucs/e 1cd can be regarded as a potential indicator for predicting the failure strain of laboratory-scale rock samples.

In this paper, we have investigated the quantitative relationship between the axial strain threshold at the volumetric strain reversal point (e1cd) and the strain threshold at the peak stress (e1ucs) during the uniaxial compression tests. We found that normalized values of e1ucs/e1cd for different rock types are typically ~1.34(±0.24). This is especially true for igneous and metamorphic rocks, or low-porosity sedimentary rocks. To verify this finding, we investigated seven granitic gneiss samples using the uniaxial compression test. Our results were consistent with the above statistics. We inferred that e1ucs/e1cd may be an intrinsic property of low-porosity rocks, and may be a potential indicator for predicting failure strains in laboratory-scale rock samples.

The response of the hypothalamic-pituitary-adrenal (HPA) axis to the sustained stress of sepsis has been the focus of study in recent years because the early phase of sepsis is known to be dominated by major alterations in the HPA axis. This prospective observational study aimed at assessing the predictive values of copeptin and HPA hormones in determining sepsis progression and mortality in the emergency department (ED).Serum arginine vasopressin (AVP) and copeptin concentrations were measured upon ED admission. Baseline levels of total and free cortisol and adrenocorticotrophic hormone (ACTH) were measured within 24 h of ED admission. Mortality in Emergency Department Sepsis (MEDS) score was calculated at enrollment.Our findings demonstrated that serum copeptin, baseline total cortisol, baseline free cortisol and baseline ACTH concentrations gradually increased, based upon the increasing severity of the disease (p0.001). Multivariate logistic regression analysis showed that copeptin and total cortisol baseline concentrations were independent predictors of septic shock (odds ratio = 1.034 and 1.355, respectively) and 28-day mortality (odds ratio = 1.039 and 1.499, respectively). The areas under the receiver operating characteristic curve (AUC) for copeptin level in prediction of septic shock was 0.856 and 28-day mortality was 0.826. Importantly, AUC analysis of the combination of copeptin, total cortisol baseline, MEDS score, and procalcitonin level resulted in a more significant prognostic ability than analysis of each parameter alone (p0.001).Increased copeptin and HPA hormones baseline levels may provide crucial information for risk stratification in a variety of septic states in the ED. Furthermore, measurements of copeptin level and serum baseline cortisol concentration are promising independent prognostic markers for mortality in patients with severe sepsis or septic shock.

(-)-Epigallocatechin gallate (EGCG) has recently been shown to exert neuroprotection in a variety of neurological diseases; however, its role and the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the potential neuroprotective effects of EGCG and the possible role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in the putative neuroprotection against experimental stroke in rats. The results revealed that EGCG exhibit significant neuroprotection, as evidenced by reduced infarction size and the decrease in transferase dUTP nick end labeling-positive neurons. Furthermore, EGCG also enhanced levels of Nrf2 and its downstream ARE pathway genes such as heme oxygenase-1, glutamate-cysteine ligase modulatory subunit and glutamate-cysteine ligase regulatory subunit, as compared to control groups. In accordance with its induction of Nrf2 activation, EGCG exerted a robust attenuation of reactive oxygen species generation and an increase in glutathione content in ischemic cortex. Taken together, these results demonstrated that EGCG exerted significant antioxidant and neuroprotective effects following focal cerebral ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.

This paper proposes a hierarchical hybrid particle swarm optimization (PSO) and differential evolution (DE) based algorithm (HHPSODE) to deal with bi-level programming problem (BLPP). To overcome the shortcomings of basic PSO and basic DE, this paper improves PSO and DE, respectively by using a velocity and position modulation method in PSO and a modified mutation strategy in DE. HHPSODE employs the modified PSO as a main program and the modified DE as a subprogram. According to the interactive iterations of modified PSO and DE, HHPSODE is independent of some restrictive conditions of BLPP. The results based on eight typical bi-level problems demonstrate that the proposed algorithm HHPSODE exhibits a better performance than other algorithms. HHPSODE is then adopted to solve a bi-level pricing and lot-sizing model proposed in this paper, and the data is used to analyze the features of the proposed bi-level model. Further tests based on the proposed bi-level model also exhibit good performance of HHPSODE in dealing with BLPP.

This paper considers the synchronization and unknown input recovery problem for a class of digital nonlinear systems based on a nonlinear observer approach. A generalized Luenberger-like observer is introduced for a class of discrete-time Lipschitz nonlinear systems. Stability conditions for the existence of asymptotic observers are established in terms of some linear matrix inequalities. It is shown that the proposed conditions are less conservative than some existing ones in the recent literature. Moreover, an observer design method is used to address the problem of H ∞ synchronization and unknown input recovery for a class of Lipschitz nonlinear systems in the presence of disturbances in both the state and output equations. Finally, a numerical example is provided to illustrate the effectiveness of the proposed design.

Bilevel programming problem (BLPP) is a NP-hard problem and very difficult to be resolved by using the classical method. This paper attempts to develop an efficient method based on improved bilevel particle swarm optimization algorithm (IBPSO) to deal with BLPP. The improved algorithm adopts dynamic self-adapting inertia weight and Cauchy distribution to ensure global search ability and faster convergence speed of IBPSO. IBPSO employs two improved PSO as a main program and a subprogram respectively. According to the interactive iterations of two improved PSO algorithms, IBPSO can solve BLPP without some assumptions of BLPP, such as the gradient information of the objective functions, the convexity of constraint regions, and so on. Twelve bilevel problems in the literatures are employed to illustrate the performance of IBPSO and some comparisons are also given. The results demonstrate that the proposed algorithm IBPSO exhibits higher accuracy than other algorithms. Then IBPSO is adopted to solve two supply chain models proposed in this paper, and some features of the proposed bilevel model are given based on the experimental data. The results support the finding that IBPSO is effective in optimizing BLPP.

As the weak part in shale formations, the bedding plane is an important element affecting the stability of boreholes and the formation of hydraulic fracture networks. To study the influence of bedding plane on the progressive failure process of rock, a series of uniaxial compressive tests were conducted on shale samples with bedding plane orientations (θ) of 0–90° with respect to the axial stress directions. The pre-peak failure process of shale observed during the tests is divided into three stages: the elastic deformation stage during which axial strains mainly occur, the stable crack growth stage during which the axial strains equal the lateral strains except for θ = 0° and 15°, and the unstable crack growth stage during which lateral strains are dominant. The peak strengths, crack damage stresses, and the corresponding strains are greatly influenced by the initial anisotropy; however, the crack initiation stresses and corresponding strain thresholds change only slightly. While the normalized lateral strain (e 3cd/e 3ucs) for the crack damage stress is strongly affected by the bedding structure, the other normalized stress and strain quantities can be used to predict the failure process of anisotropic rocks. The newly developed measure of brittleness index m, determined by the peak strength, peak axial strain, and elastic modulus, reflects the whole progressive failure process and was verified in the tests as a reasonable and accurate index.

P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83-1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82-0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80-0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80-0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78-0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78-0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.

A dual-level direct dynamic study has been employed to investigate the H-abstraction reaction of morpholine (C4H9NO) with OH. The chair conformer of C4H9NO molecule is performed as the reactant because of the lower energy. The potential energy surfaces are obtained at the MC-QCISD/3//M06-2X/6-311+G(d, p) level. The rate constants are estimated using the improved canonical variational transition state theory with the small-curvature tunneling correction over a wide temperature range of 200 to 1000 K, and a fitted four-parameter rate constant expression is obtained. The calculated rate constants are in good agreement with the available experimental values, and the negative temperature dependence of rate constant is found within 200–600 K. Moreover, the contribution of each reaction site to the title reaction is discussed with respect to the temperature. The result shows that the H-abstraction reaction mainly takes place at the –CH2 group attached to the N atom at low temperatures, while as the temperature increases the contribution of the H-abstraction to the title reaction from the –NH group becomes larger rapidly, and the –NH group turns into the most important H-abstraction reaction site when the temperature is higher than 800 K.

Background Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. Sildenafil has been shown to attenuate postresuscitation myocardial dysfunction in piget models of ventricular fibrillation. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by attenuating apoptosis and regulating miRNA expressions, furthermore, ameliorating the severity of post-microcirculatory dysfunction. Methods Twenty-four male pigs (weighing 30 ± 2 kg) were randomly divided into groups, sildenafil pretreatment (n = 8), saline (n = 8) and sham operation (sham, n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil, administered once intraperitoneally 30 min prior to ventricular fibrillation (VF). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and hearts were removed for analysis by electron microscopy, western blotting, quantitative real-time polymerase chain reaction (PCR), and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Intestinal microcirculatory blood flow was visualized by a sidestream dark-field imaging device at baseline and 0.5, 1, 2, 4, and 6 h after ROSC. Results Compared with the saline group, the sildenafil group had a higher 24-hour survival (7/8 versus 3/8 survivors, p

High-temperature phase-stable rice-like anatase TiO2 nanocrystals were synthesized by one-pot solvothermal method using soluble titania xerogel and isopropyl alcohol (IPA) as the precursor and the solvent, respectively. Sample characterization was carried out by powder X-ray diffraction, high-resolution transmission electron microscopy, field emission scanning electron microscope, X-ray photoelectron spectroscopy, and N2 adsorption–desorption isotherms. The results showed that TiO2 nanocrystals had rice-like shapes with an average size of 5 nm in width and 35 nm in length. The BET surface area was 153 m2/g. Unexpectedly, the rice-like TiO2 nanocrystals exhibited high-temperature phase stability, which could remain as pure anatase phase after calcinations at 1000 °C. Growth mechanism investigation revealed that the IPA solvent played a key role in nucleation and growth of rice-like anatase TiO2 nanocrystals. The photodegradation of rhodamine B demonstrated that rice-like anatase TiO2 nanocrystals exhibited enhanced photocatalytic activity under visible light irradiation.

Introduction Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism. Methods Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation. Results After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P

Introduction The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED). Methods In total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients. Results The median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days’ follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group. Conclusions NGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.