Description: Background: Plants attenuate their responses to a variety of bacterial and fungal pathogens, leading to higher incidences of pathogen infection at night. However, little is known about the molecular mechanism responsible for the light-induced defence response; transcriptome data would likely facilitate the elucidation of this mechanism. Results: In this study, we observed diurnal changes in tomato resistance to Pseudomonas syringae pv. tomato DC3000 (Pto DC3000), with the greatest susceptibility before midnight. Nightly light treatment, particularly red light treatment, significantly enhanced the resistance; this effect was correlated with increased salicylic acid (SA) accumulation and defence-related gene transcription. RNA-seq analysis revealed that red light induced a set of circadian rhythm-related genes involved in the phytochrome and SA-regulated resistance response. The biosynthesis and signalling pathways of multiple plant hormones (auxin, SA, jasmonate, and ethylene) were co-ordinately regulated following Pto DC3000 infection and red light, and the SA pathway was most significantly affected by red light and Pto DC3000 infection. This result indicates that SA-mediated signalling pathways are involved in red light-induced resistance to pathogens. Importantly, silencing of nonexpressor of pathogensis-related genes 1 (NPR1) partially compromised red light-induced resistance against Pto DC3000. Furthermore, sets of genes involved in redox homeostasis (respiratory burst oxidase homologue, RBOH; glutathione S-transferases, GSTs; glycosyltransferase, GTs), calcium (calmodulin, CAM; calmodulin-binding protein, CBP), and defence (polyphenol oxidase, PPO; nudix hydrolase1, NUDX1) as well as transcription factors (WRKY18, WRKY53, WRKY60, WRKY70) and cellulose synthase were differentially induced at the transcriptional level by red light in response to pathogen challenge. Conclusions: Taken together, our results suggest that there is a diurnal change in susceptibility to Pto DC3000 with greatest susceptibility in the evening. The red light induced-resistance to Pto DC3000 at night is associated with enhancement of the SA pathway, cellulose synthase, and reduced redox homeostasis.

Description: Background: Alcohol consumption has been inconsistently associated with the risk of ovarian cancer. The purpose of this study was to summarize the data from prospective cohort studies on the relationship between alcohol consumption and ovarian cancer using a meta-analytic approach. Methods: We performed electronic searches of PubMed, Embase, and the Cochrane Library in May 2014 to identify studies that examined the effects of alcohol consumption on the incidence of ovarian cancer. Only prospective cohort studies that reported effect estimates about the incidence of ovarian cancer with 95% confidence intervals (CIs) of alcohol intake were included. Results: Collectively, we included 13 prospective studies that reported on data from 1,996,841 individuals and included 5,857 cases of ovarian cancer. Alcohol consumption had little to no effect on ovarian cancer incidence when compared to non-drinkers (risk ratio [RR], 1.03; 95% CI, 0.96–1.10; P = 0.473). Similarly, low (RR, 0.96; 95% CI, 0.93–1.00; P = 0.059), moderate (RR, 1.08; 95% CI, 0.92–1.27; P = 0.333), and heavy (RR, 0.99; 95% CI, 0.88–1.12; P = 0.904) alcohol consumption was not associated with the risk of ovarian cancer. Furthermore, subgroup analyses suggested that low alcohol intake was associated with a reduced risk of ovarian cancer whereas heavy alcohol intake was associated with an increased risk of ovarian cancer in multiple subpopulations. Conclusions: Our study suggests that alcohol intake is not associated with an increased risk of ovarian cancer. Subgroup analyses indicated that alcohol consumption might be associated with the risk of ovarian cancer in specific population or in studies with specific characteristics.

Description: Aims Toll-like receptor 7 (TLR7) agonists has been applied into cancer immunotherapy, but the heterogeneity of tumor renders TLR7 behaves versatile in tumor microenvironment and the characteristic of TLR7 in oral squamous cell carcinoma (OSCC) is unclear. Methods and results 20 healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR7 in tumor cells (TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR7 in stroma fibroblast-like cells (FLCs) had low tumor stage, no lymph node metastasis (LNM) and better prognosis. Furthermore, ki-67, CD3, CD4, CD8 and Foxp3 + tumor-infiltrated lymphocytes were assessed and found that TLR7 high TCs were infiltrated with fewer CD3 + CD4 + but more Foxp3 + lymphocytes. Importantly, patients with TLR7 low TCs and TLR7 high FLCs had less Foxp3 + lymphocytes infiltration and longer survival time than those who with TLR7 high TCs/TLR7 low FLCs, although TLR7 was not an independent prognostic factor for OSCC. Conclusions The low expression of TLR7 in tumor and high expression of TLR7 in stroma predict a good clinical outcome for OSCC patients and stroma FLCs might be conducive to immunotherapy by TLR7 agonist. This article is protected by copyright. All rights reserved.

Description: Soil respiration in water-limited ecosystems is affected intricately by soil water content (SWC), temperature, and soil properties. Eight sites on sand-fixed dunes revegetated in different years since1950s, with several topographical positions and various biological soil crusts (BSCs) and soil properties, were selected, as well as a moving sand dune (MSD) and a reference steppe in the Tengger Desert of China. Intact soil samples of 20 cm in depth were taken and incubated randomly at twelve levels of SWC (0 to 0.4 m 3 m −3 ) and at nine levels of temperature (5 to 45 °C) in a growth chamber; additionally, cryptogamic and microbial respiration (R M ) were measured. Total soil respiration (R T , including cryptogamic, microbial, and root respiration) was measured for two years at the MSD and five sites of sand-fixed dunes. The relationship between R M and SWC under the optimal SWC condition (0.25 m 3 m −3 ) is linear, as is the entire range of R T and SWC. The slope of linear function describes sensitivity of soil respiration to water (SRW) and reflects to soil water availability, which is related significantly to soil physical properties, BSCs, and soil chemical properties, in decreasing importance. Inversely, Q 10 for R M is related significantly to abovementioned factors in increasing importance. However, Q 10 for R T and respiration rate at 20 °C are related significantly to soil texture and depth of BSCs and subsoil only. In conclusion, through affecting SRW, soil physical properties produce significant influences on soil respiration, especially for R T . This indicates that a definition of the biophysical meaning of SRW is necessary, considering the water-limited and coarse-textured soil in most desert ecosystems.

Description: Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of invasive breast cancer in which approximately half the patients will progress to invasive cancer. Gaining a better understanding of DCIS progression may reduce overtreatment of patients. Expression of the pro-inflammatory cytokine interleukin-6 increases with pathological stage and grade, and is associated with poorer prognosis in breast cancer patients. Carcinoma associated fibroblasts (CAFs), which are present in the stroma of DCIS patients are known to secrete pro-inflammatory cytokines and promote tumor progression. Methods: We hypothesized that IL-6 paracrine signaling between DCIS cells and CAFs mediates DCIS proliferation and migration. To test this hypothesis, we utilized the mammary architecture and microenvironment engineering or MAME model to study the interactions between human breast CAFs and human DCIS cells in 3D over time. We specifically inhibited autocrine and paracrine IL-6 signaling to determine its contribution to early stage tumor progression. Results: Here, DCIS cells formed multicellular structures that exhibited increased proliferation and migration when cultured with CAFs. Treatment with an IL-6 neutralizing antibody inhibited growth and migration of the multicellular structures. Moreover, selective knockdown of IL-6 in CAFs, but not in DCIS cells, abrogated the migratory phenotype. Conclusion: Our results suggest that paracrine IL-6 signaling between preinvasive DCIS cells and stromal CAFs represent an important factor in the initiation of DCIS progression to invasive breast carcinoma.

Description: IntroductionThere are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized. Methods: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers. Results: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification. Conclusion: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.

Description: Background: I t is established that adipose-derived stem cells (ADSCs) produce and secrete cytokines/growth factors that antagonize mucosal injury. However, the exact molecular basis underlying the treatment effects exerted by ADSCs is ill understood, and whether ADSCs cooperate with adipose tissue particles to improve mucosal function in patients with empty nose syndrome (ENS) has not been explored. We investigated the impact of ADSCs on nasal mucosa, the associated mechanisms, and their use in the treatment of patients with ENS. Results: The nasal endoscope and mucociliary clearance assessments were significantly improved (P 

Description: ABSTRACT We propose new implicit staggered-grid finite-difference schemes with optimal coefficients based on the sampling approximation method to improve the numerical solution accuracy for seismic modelling. We first derive the optimized implicit staggered-grid finite-difference coefficients of arbitrary even-order accuracy for the first-order spatial derivatives using the plane-wave theory and the direct sampling approximation method. Then, the implicit staggered-grid finite-difference coefficients based on sampling approximation, which can widen the range of wavenumber with great accuracy, are used to solve the first-order spatial derivatives. By comparing the numerical dispersion of the implicit staggered-grid finite-difference schemes based on sampling approximation, Taylor series expansion, and least squares, we find that the optimal implicit staggered-grid finite-difference scheme based on sampling approximation achieves greater precision than that based on Taylor series expansion over a wider range of wavenumbers, although it has similar accuracy to that based on least squares. Finally, we apply the implicit staggered-grid finite difference based on sampling approximation to numerical modelling. The modelling results demonstrate that the new optimal method can efficiently suppress numerical dispersion and lead to greater accuracy compared with the implicit staggered-grid finite difference based on Taylor series expansion. In addition, the results also indicate the computational cost of the implicit staggered-grid finite difference based on sampling approximation is almost the same as the implicit staggered-grid finite difference based on Taylor series expansion.

Description: Background: Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature of AML. GATA4 has been suggested to be a tumor suppressor gene regulated by promoter hypermethylation in various types of human cancers although the expression and promoter methylation of GATA4 in pediatric AML is still unclear. Methods: Transcriptional expression levels of GATA4 were evaluated by semi-quantitative and real-time PCR. Methylation status was investigated by methylation-specific PCR (MSP) and bisulfate genomic sequencing (BGS). The prognostic significance of GATA4 expression and promoter methylation was assessed in 105 cases of Chinese pediatric acute myeloid leukemia patients with clinical follow-up records. Results: MSP and BGS analysis showed that the GATA4 gene promoter is hypermethylated in AML cells, such as the HL-60 and MV4-11 human myeloid leukemia cell lines. 5-Aza treatment significantly upregulated GATA4 expression in HL-60 and MV4-11 cells. Aberrant methylation of GATA4 was observed in 15.0 % (3/20) of the normal bone marrow control samples compared to 56.2 % (59/105) of the pediatric AML samples. GATA4 transcript levels were significantly decreased in AML patients (33.06 ± 70.94; P = 0.011) compared to normal bone marrow/idiopathic thrombocytopenic purpura controls (116.76 ± 105.39). GATA4 promoter methylation was correlated with patient leukocyte counts (WBC, white blood cells) (P = 0.035) and minimal residual disease MRD (P = 0.031). Kaplan-Meier survival analysis revealed significantly shorter overall survival time in patients with GATA4 promoter methylation (P = 0.014). Conclusions: Epigenetic inactivation of GATA4 by promoter hypermethylation was observed in both AML cell lines and pediatric AML samples; our study implicates GATA4 as a putative tumor suppressor gene in pediatric AML. In addition, our findings imply that GATA4 promoter methylation is correlated with WBC and MRD. Kaplan-Meier survival analysis revealed significantly shorter overall survival in pediatric AML with GATA4 promoter methylation but multivariate analysis shows that it is not an independent factor. However, further research focusing on the mechanism of GATA4 in pediatric leukemia is required.

Description: Shear stress provided by a hydrocyclone was employed to remove the oil from oil-contaminated catalysts. Understanding the deoiling mechanism and providing quantitative analysis of the interaction between shear stress fields and deoiling are necessary to improve deoiling efficiency. In this study, a numerical simulation was conducted for the velocity field and shear stress field of a hydrocyclone, both of which are difficult to measure using other methods. Results showed that the shear stress field in the wall layer, where oil-contaminated catalysts are usually located, was robust. Increasing inlet flow rates resulted in a higher shear rate distribution along the wall layer. Numerical results were also compared with the experimental data. In the deoiling process, higher shear stress rates promoted faster transport of oil from catalysts into the fluid, thereby increasing the deoiling efficiency. Deoiling by the shear stress of a hydrocyclone is an efficient method for cleaning oil-contaminated catalysts within a short period of time.