Protein Kinase D (PKD) family contains PKD1, PKD2, and PKD3 in human. Compared to consistent tumor-suppressive functions of PKD1 in breast cancer, how PKD2/3 functions in breast cancer are not fully understood. In the current study, we found that PKD2 and PKD3 but not PKD1 were preferentially overexpressed in breast cancer and involved in regulating cell proliferation and metastasis. Integrated phosphoproteome, transcriptome, and interactome showed that PKD2 was associated with multiple cancer-related pathways, including adherent junction, regulation of actin cytoskeleton, and cell cycle-related pathways. ELAVL1 was identified as a common hub-node in networks of PKD2/3-regulated phosphoproteins and genes. Silencing ELAVL1 inhibited breast cancer growth in vitro and in vivo. Direct interaction between ELAVL1 and PKD2 or PKD3 was demonstrated. Suppression of PKD2 led to ELAVL1 translocation from the cytoplasm to the nucleus without significant affecting ELAVL1 expression. Taken together, we characterized the oncogenic functions of PKD2/3 in breast cancer and their association with cancer-related pathways, which shed lights on the oncogenic roles and mechanisms of PKDs in breast cancer.

This review presents the synergistic effect in the catalytic system of ionic liquids (ILs) for the synthesis of cyclic carbonate from carbon dioxide and epoxide. The emphasis of this review is on three aspects: the catalytic system of metal-based ionic liquids, the catalytic system of hydrogen bond-promoted ionic liquids and supported ionic liquids. Metal and ionic liquids show a synergistic effect on the cycloaddition reactions of epoxides. The cations and anions of ionic liquids show a synergistic effect on the cycloaddition reactions. The functional groups in cations or supports combined with the anions have a synergistic effect on the cycloaddition reactions. Synergistic catalytic effects of ILs play an important role of promoting the cycloaddition reactions of epoxides. The design of catalytic system of ionic liquids will be possible if the synergistic effect on a molecular level is understood.

BACKGROUND: Relatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels.; METHODS: Participants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay.; RESULTS: In the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference (p<0.01, p<0.01, respectively). Scores of Neonatal Behavioral Neurological Assessment were significantly reduced (p<0.001). Cord plasma ACTH, norepinephrine, and epinephrine levels were significantly increased (p<0.001), but cortisol levels were reduced (p<0.001).; CONCLUSION: Prenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine. Copyright =C2=A9 2015. Published by Elsevier B.V.

Rockfall disasters occur frequently in mountainous areas of western China, and the rockfall disasters along a railway line will seriously affect the safety and normal operation of railways, causing great economic and property losses. Existing rockfall monitoring and early warning methods still have shortcomings, such as accurate warning of single-point disasters and vulnerability to the natural environment. In this study, a rockfall test of a flexible safety protection net along the slope of a railway and a rockfall test of the railway track were carried out, and the vibration signals of the falling rock hitting the different sites of the protective net and hitting different positions of the rails were obtained. Using the signal analysis methods such as Fast Fourier Transformation and Short-Time Fourier Transform, the basic characteristics of the rockfall vibration signal and the vibration signal when the train passes and the propagation law of the rockfall vibration signal are obtained. Finally, a set of monitoring and early warning systems for rockfall disasters along the railway based on the analysis of vibration signal characteristics is established. The monitoring and early warning method has the advantages of all-weather, high-time, semi-automatic and high efficiency performance.

In this study, we first characterized the complete mitogenome of Pygathrix nigripes, and analysed its phylogenetic status. The circular mitogenome was 16,534bp in length, and contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and one non-coding control region (D-loop). These genes except ND6 and 8 tRNA genes were encoded on the H-strand. The phylogenetic analysis exhibited that our sequence formed a sister branch with P. cinereal and P. nemaeus of genus Pygathrix, which showed a closer genetic relationship of the three species. These information contribute to molecular, phylogenetic studies and genetic diversity conservation for this species.

Malus hupehensis Rehd. is often used as rootstock of apple trees. Vacuolar processing enzyme (VPE) is one type of cysteine protease with substrate specificity to residues of asparagine and aspartic acid. The VPE activity, MhVPE gamma gene (GenBank number: FJ891065) expression and the amount of cell death in seedlings of M. hupehensis Rehd. all gradually increased with the increase of temperature from 26 to 42 degrees C. To explore the function of VPE response to temperature stress, the overexpressing vector of MhVPE gamma was constructed and transformed into wild-type Arabidopsis thaliana Columbia. The responses of VPE, MhVPE gamma and apoptosis to high temperature stress were determined in the Arabidopsis seedlings of wild-type, MhVPE gamma-overexpressing lines and the VPE-null mutant. The leaves of MhVPE gamma-overexpressing lines were smaller and VPE activity and MhVPE gamma expression level were both obviously higher than the levels found in the wild-type and VPE-null mutant seedlings. Under high temperature treatment, VPE activity and MhVPE gamma expression level significantly increased accompanied by leaf withering, shorter roots, lipid peroxidation and increased cell death and apoptosis rate in all types of plants. The changes of these indicators were highest in MhVPE gamma-overexpressing transgenic plants, followed by the wild-type and were lowest in VPE-null mutant plants. These results suggest that MhVPE gamma overexpression in Arabidopsis accelerated cell membrane lipid peroxidation, promoted cell death and reduced the tolerance to high temperature stress compared with wild-type plants.

Microphthalmia-associated transcription factor (MITF) plays a crucial role in the melanogenesis and proliferation of melanocytes that is dependent on its abundance and modification. Here, we report that epidermal growth factor (EGF) induces senescence and cyclin-dependent kinase inhibitor 1A (CDKN1A) expression that is related to MITF. We found that MITF could bind TP53 to regulate CDKN1A. Furthermore, the interaction between MITF and TP53 is dependent on AKT activity. We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Meanwhile, the unphosphorylative MITF promotes TYR expression. The levels of p-MITF-S510 are low in 90% human melanoma samples. Thus the level of p-MITF-S510 could be a possible diagnostic marker for melanoma. Our findings reveal a mechanism for regulating MITF functions in response to EGF stimulation and suggest a possible implementation for preventing the over proliferation of melanoma cells. (C) 2016 The Authors. Published by Elsevier Ltd.

Evidence suggests long-term chronic inflammation, as the pathological basis of formation and development, plays an important part in atherosclerosis. Immunoglobulins (Igs) provided key information on the humoral immune status. However, few studies have evaluated the correlation between Igs and hypertension and blood pressure (BP) in a general population. We designed a cross-sectional study to evaluate whether serum Ig levels are related to BP and the prevalence of hypertension. About 12,373 participants in Tianjin, China were recruited for this study. Hypertension was diagnosed according to the criteria of the JNC 7 and serum levels of Igs were determined by the immunonephelometric technique. Multiple logistic regression analysis and analysis of covariance were used to assess relationships between serum Ig concentrations and the prevalence of hypertension and BP. The overall prevalence of hypertension was 35.5%. The means (standard deviation) of immunoglobulins [immunoglobulin G (IgG), immunoglobulin E (IgE), immunoglobulin M (IgM), and immunoglobulin A (IgA)] were 1206.0 (249.0) mg/dL, 93.8 (235.4) IU/mL, 105.3 (56.8) mg/dL, and 236.7 (98.1) mg/dL, respectively. The multivariable-adjusted odds ratios (95% confidence interval) of hypertension for the highest immunoglobulins (IgG, IgE, IgM, and IgA) quintile, when compared to the lowest quintile were 1.10 (0.96-1.26), 1.04 (0.91-1.19), 0.83 (0.72-0.96), and 1.32 (1.15-1.51), respectively. Decreased IgM and increased IgG and IgA were related to a higher prevalence of hypertension. IgM was negatively correlated with BP, while IgG and IgA were positively correlated with BP.=20

Purpose Excessive consumption of soft drinks is associated with nonalcoholic fatty liver disease (NAFLD). However, the association between soft drinks consumption and NAFLD is unclear in non-Caucasian adults with relatively low soft drinks consumption. The aim of this study was to assess the association between soft drinks consumption and NAFLD in Chinese adults. Methods A cross-sectional study was conducted with 26,790 adults living in Tianjin, China. NAFLD (with elevated alanine aminotransferase [ALT]) was diagnosed by the liver ultrasonography and serum ALT concentrations. Soft drinks consumption was assessed using a validated self-administered food frequency questionnaire, and it was summarized as three categories for analysis: almost never reference), < 1 cup/week, and >=3D 1 cups/week. Metabolic syndrome (MetS) was defined according to the criteria of the American Heart Association scientific statements of 2009. The association between soft drinks consumption and NAFLD was assessed by multiple logistic regression analysis. Results The prevalence of NAFLD and NAFLD with elevated ALT was 27.1 and 6.5%, respectively. After adjustment for potential confounding variables (including MetS), the odds ratios (95% confidence intervals) for NAFLD or NAFLD with elevated ALT across soft drinks consumption were 1.00 (reference) for almost never, 1.14 (1.02-1.27) or 1.16 (0.98-1.37) for < 1 cup/week, and 1.26 (1.14-1.40) or 1.32 (1.13-1.53) for >=3D 1 cups/week (both P for trend <0.001), respectively. Conclusions This is the first study to demonstrate that soft drinks consumption is associated with NAFLD independent of MetS in Chinese adults with relatively low soft drinks consumption. These results suggest that reducing soft drinks consumption might be beneficial to the prevention of NAFLD.

The subgrade bed, which serves as an important foundation for supporting the slab track structure of high-speed railways, is usually filled with the graded crushed stone. The infiltration of rainwater into the graded crushed stone in the subgrade bed through cracks in the expansion joints can have a negative impact on the dynamic performance of the subgrade bed to affect the operational comfort and safety of high-speed rail travel. To prevent water from infiltrating into the subgrade bed, this study proposes a new waterproof seal layer made of the polyurethane polymer-improved gravels, which is placed on the surface of the subgrade bed. A variety of laboratory tests were performed to analyze the mixture parameters of the polyurethane polymer-improved gravels. A suitable gradation of the gravel used for the polyurethane polymer-improved gravels and its optimum composition were determined based on the test results employed in this research. In addition, two experimental models were established to investigate the dynamic and waterproofing performance of the subgrade bed with and without the new waterproof seal layer under cyclic dynamic loading. According to the model test results, the subgrade bed covered by the new waterproof seal layer displayed significantly better performance compared with that of the conventional subgrade bed when water was poured on the surface of the subgrade bed during cyclic dynamic loading. (C) 2019 Published by Elsevier Ltd.

Tumor suppressor PTEN regulates cellular activities and controls genome stability through multiple mechanisms. In this study, we report that PTEN is necessary for the protection of DNA replication forks against replication stress. We show that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea. PTEN is physically associated with replication protein A 1 (RPA1) via the RPA1 C-terminal domain. STORM and iPOND reveal that PTEN is localized at replication sites and promotes RPA1 accumulation on replication forks. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. RPA1 deletion confers a phenotype like that observed in PTEN knockout cells with stalling of replication forks. Expression of PTEN and RPA1 shows strong correlation in colorectal cancer. Heterozygous disruption of RPA1 promotes tumorigenesis in mice. These results demonstrate that PTEN is essential for DNA replication fork protection. We propose that RPA1 is a target of PTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.

Background: Metabolic syndrome (MetS) is a cluster of cardiovascular and metabolic risk factors in the same individual. Inflammation has been reported to be directly involved in the development of metabolic disease. Complement component 3 (C3) and complement component 4 (C4) have been identified as important inflammatory markers relevant to metabolic disease. However, few studies have analyzed the association between C3 and/or C4 and MetS. In this study, our aim is to evaluate sex-specific association between C3 and C4 levels and risk of MetS in an adult population. Methods: A cohort of 4635 adults was followed from 2010 to 2016. Serum C3 and C4 levels were measured using an immunonephelometric technique. MetS was defined by the American Heart Association scientific statements of 2009. Cox proportional hazard regression models were used to assess sex-specific association between C3 and C4 levels and the incidence of MetS. Results: During the approximate to 6 years of follow-up, 1445 new cases of MetS were identified. After being adjusted to confounding factors, the hazard ratios (95% confidence interval) of MetS for gradually increasing quintiles of C3 were 1.00, 1.23 (0.98-1.54), 1.50 (1.21-1.87), 1.64 (1.32-2.04), and 1.75 (1.41-2.18) (P for trend <0.0001) in men and 1.00, 0.96 (0.60-1.53), 1.61 (1.06-2.44), 2.01 (1.34-3.03), and 2.43 (1.63-3.63) (P for trend <0.0001) in women, respectively. Similar results were also obtained for gradually increasing quintiles of C4 in women, but not in men. Conclusions: The levels of C3 were significantly associated with the incidence of MetS in both men and women. The levels of C4 contributed to risk of MetS only in women.

In view of the limited use of foam concrete for backfilling high-speed railway bridge approach and no publication considering the associated foundation treatment cost, this article presents a series of laboratory tests to study the mechanical properties of fiberglass-reinforced foam concrete with different contents of fiberglass, whereby the optimal values of target density and fiberglass content for fiberglass-reinforced foam concrete are obtained. A numerical model is developed to investigate the performance of bridge approach filled with fiberglass-reinforced foam concrete under different levels of foundation treatment in comparison with the control group with traditional backfills (combination of graded crushed stone and cement). Results indicate that the application of fiberglass-reinforced foam concrete to fill high-speed railway bridge approach can significantly improve the bridge approach performance (decreasing the horizontal displacement and ground surface settlement, respectively, by 58% and 21% than the control group) and cut down the foundation treatment cost by 19% concurrently.

BACKGROUND: Hypertension is a significant global public health challenge. Low-grade inflammation is known to facilitate the development of essential hypertension and target-organ hypertensive damage. Neutrophil to lymphocyte ratio (NLR) is a simple and reliable indicator of inflammation that may also be useful in the prediction of hypertension.; METHODS: Participants were recruited from Tianjin Medical University's General Hospital-Health Management Centre. A total of 28,850 initially hypertension-free subjects were followed from 2007 to 2013. Adjusted Cox proportional hazards regression models were used to assess relationships between NLR categories and incidence of hypertension.; RESULTS: During the ~6-year follow-up period (median duration of follow-up (interquartile range): 2.63 (2.58-2.68)), 1,824 subjects developed hypertension. The hazard ratios of hypertension incidence were evaluated in increasing NLR quintiles. Compared with participants with the lowest NLR levels, the multivariable-adjusted hazard ratios (95% confidence interval) of hypertension were related to increasing NLR quintiles and were as follows: 1.08 (0.92, 1.26), 0.97 (0.83, 1.14), 1.10 (0.94, 1.28), and 1.23 (1.06, 1.43), respectively (P for trend < 0.01). Similar results also were observed in the white blood cell and neutrophil counts, but not lymphocyte counts.; CONCLUSIONS: The study is the first to show the elevated NLR levels significantly correlate with an increased risk of developing hypertension. This result may be useful in elucidating the mechanism underlying the development of hypertension. New therapeutic approaches aimed at inflammation might be proposed to control hypertension and hypertensive damage. =C2=A9 American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Histochemical staining and RNA-seq data demonstrated that the ROS- and plant hormone-regulated stress responses are the key early events of narciclasine signaling in Arabidopsis root cells.Narciclasine, an amaryllidaceae alkaloid isolated from Narcissus tazetta bulbs, employs a broad range of functions on plant development and growth. However, its molecular interactions that modulate these roles in plants are not fully understood. To elucidate the global responses of Arabidopsis roots to short-term narciclasine exposure, we first measured the accumulation of H2O2 and O-2 (-) with histochemical staining, and then profiled the gene expression pattern in Arabidopsis root tips treated with 0.5 A mu M narciclasine across different exposure times by RNA-seq. Physiological measurements showed a significant increase in H2O2 began at 30-60 min of narciclasine treatment and O-2 (-) accumulated by 120 min. Compared with controls, 236 genes were upregulated and 54 genes were downregulated with 2 h of narciclasine treatment, while 968 genes were upregulated and 835 genes were downregulated with 12 h of treatment. The Gene Ontology analysis revealed that the differentially expressed genes were highly enriched during oxidative stress, including those involved in the "regulation of transcription", "response to oxidative stress", "plant-pathogen interaction", "ribonucleotide binding", "plant cell wall organization", and "ribosome biogenesis". Moreover, Kyoto Encyclopedia of Genes and Genomes pathway enrichment statistics suggested that carbohydrate metabolism, amino acid metabolism, amino sugar and nucleotide sugar metabolism, and biosynthesis of phenylpropanoid and secondary metabolites were significantly inhibited by 12 h of narciclasine exposure. Hence, our results demonstrate that hormones and H2O2 are important regulators of narciclasine signaling and help to uncover the factors involved in the molecular interplay between narciclasine and phytohormones in Arabidopsis root cells.

Pavement skid resistance plays a key role in traffic safety. Meanwhile, tire-pavement noise is a major source of traffic noise in urban areas. Current asphalt mixture design methods, however, mostly focus on volumetric and mechanical properties and pay little attention to the skid resistance and noise reduction performance of asphalt mixtures, which are significantly affected by the surface textures of asphalt mixtures. Incorporating the evaluation of surface texture into the mixture design would aid in a more rational selection of materials considering both mechanical and functional properties of asphalt mixtures. In this paper, the surface texture properties of several types of asphalt mixtures are measured using a recently developed 2-Dimensional Image Texture Analysis Method. A prediction model correlating the mixture surface texture levels at different central texture wavelength in octave band with the important mix design parameters is established using a multivariate non-linear regression analysis. The model is validated through laboratory test and imaging measurement indicating its capability of predicting the level and distributions of mixture surface texture. The prediction model is anticipated to provide a basis of optimised mixture design considering the skid resistance and noise reduction performances of asphalt pavement.