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Fusarium crown rot of wheat has become more prevalent in China. To investigate the phylogenetic structure of Fusarium causing wheat crown rot in China, wheat basal stems with symptoms of the disease were collected from 2009 to 2013 in Jiangsu, Anhui, Henan, Hebei, and Shandong provinces. In total, 175 Fusarium isolates were collected and their mycotoxin chemotypes and distribution were identified. Among the 175 isolates, 123 were Fusarium asiaticum; 95 of these were the chemotype 3-acetyl-deoxynivalenol (3-AcDON) and 28 were nivalenol (NIV). Thirty-seven isolates belonged to F. graminearum, which were all 15-AcDON. Smaller numbers of isolates consisted of F. acuminatum, F. pseudograminearum, and F. avenaceum. The virulence of F. asiaticum and F. graminearum isolates on wheat crowns and heads was comparable. The virulence of isolates of the DON and NIV chemotype were statistically similar, but DON tended to be more aggressive. The DON concentrations in grains from wheat heads inoculated with isolates causing either Fusarium head blight or crown rot were similar. In the five provinces, F. asiaticum of the 3-AcDON chemotype was the predominant pathogen causing crown rot, followed by F. graminearum. Recent changes in causal Fusarium species, chemotypes, and distribution in China are discussed. [ABSTRACT FROM AUTHOR]

Background: CD166, an adhesion molecule of the immunoglobulin superfamily, is one of the crucial effectors that traffic lymphocytes into tissues. Till now, the expression and role of CD166 in the chronic kidney disease remains unknown. Objectives: In the present study, we are to examine the expression of CD166 in the chronic kidney disease, and to explore its function with CD4+ T cells. Materials and Methods: CD166 expression was tested by Flow Cytometry (FACS) in the primary macrophages stimulated with LPS. In vivo, the expression of CD166 and CD4 were examined in the kidney tissues of adriamycin-induced nephropathy (AN) mice by immnohistochemistry. Macrophages and lymphocytes were co-cultured, the interaction between CD166 and CD4 was tested by immunofluorescent staining. Furthermore, the effects of CD166 on the activation and proliferation of T cells were explored. Results: In this study, CD166 expression was found to be upregulated on activated macrophages and glomerular endothelia in the adriamycin-induced nephropathy (AN) mice and CD4+ T cells were increased with CD166 expression in the AN mice. The interaction between macrophages and CD4+ T cells indicated that CD166 played a key role in the recruitment of lymphocytes in the chronic kidney disease, and neither proliferation nor activation of T cells was affected by CD166. Conclusions: CD166 expressed on macrophages and endothelia in AN kidney, and the function was related to the recruitment of CD4+ T cells into inflamed kidney, indicating that CD166 may be a potential target for reducing the inflammatory infiltrates in the chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Centipeda minima (Ebushicao) has been used for the treatment of various diseases, such as nasal allergies, rhinitis and sinusitis, nasopharyngeal carcinoma, cough, and headache. This study aims to investigate the anticancer activities of Centipeda minima ethanol extracts (CME) against nasopharyngeal carcinoma cell CNE-1 and their underlying mechanism. Methods: CNE-1 cells were treated with diferent concentrations (15-50 µg/mL) of CME for diferent time intervals (24, 48, and 72 h). Cytotoxicity of CME was determined by MTT assay. Cell morphological changes were observed by luorescence microscopy after HO 33258 staining. Cell cycle status was evaluated by low cytometry following propidium iodide staining. Apoptosis was detected by low cytometry following annexin V-FITC/PI staining. The levels of apoptosis-associated and PI3K-Akt-mTOR signaling related proteins were measured by western blotting analysis. Results: CME (15-50 µg/mL) signiicantly inhibited the proliferation of CNE-1 in a dose- and time-dependent manner (P = 0.026 for 15 µg/mL, P < 0.001 for 25, 30, 40, and 50 µg/mL, respectively); the IC50 values (µg/mL) were 41.57 ± 0.17, 30.34 ± 0.06 and 24.98 ± 0.08 for 24, 48 and 72 h treatments, respectively. Signiicant morphological changes of CNE-1 cells displaying apoptosis were observed after CME treatment. CME showed low cytotoxicity toward normal LO2 cells. CNE-1 cells were arrested in the G2/M phase while treated with 15, 25, 40 µg/mL of CME, respectively (P = 0.032, P = 0.0053, P < 0.001). CME (15, 25, 40 µg/mL) down-regulated Bcl-2 expression (P = 0.032, P = 0.0074, P < 0.001), and up-regulated Bax (P = 0.026, P = 0.0056, P < 0.001) with activation of caspase-3, caspase-8, caspase-9, and PARP observed in CNE-1 cells (P = 0.015, P = 0.0067, P < 0.001 for caspase 3; P = 0.210, 0.028, < 0.001 for caspase 8; P = 0.152, 0.082, 0.0080 for caspase 9; P = 0.265, 0.0072, < 0.001 for PARP). CME suppressed the activation of the PI3K-AKT-mTOR pathway (P = 0.03, 0.0007, 0.004, 0.006, 0.022 for p-PI3K, p-Akt-Ser473, p-Akt-Thr308, p-mTOR-Ser2448, p-mTOR-Ser2481, respectively after 40 µg/mL of CME treated for 24 h). Conclusion: CME inhibited the proliferation of CNE-1 cells and activation of the PI3K-AKT-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Centipeda minima (Ebushicao) has been used for the treatment of various diseases, such as nasal allergies, rhinitis and sinusitis, nasopharyngeal carcinoma, cough, and headache. This study aims to investigate the anticancer activities of Centipeda minima ethanol extracts (CME) against nasopharyngeal carcinoma cell CNE-1 and their underlying mechanism. Methods: CNE-1 cells were treated with diferent concentrations (15-50 µg/mL) of CME for diferent time intervals (24, 48, and 72 h). Cytotoxicity of CME was determined by MTT assay. Cell morphological changes were observed by luorescence microscopy after HO 33258 staining. Cell cycle status was evaluated by low cytometry following pro- pidium iodide staining. Apoptosis was detected by low cytometry following annexin V-FITC/PI staining. The levels of apoptosis-associated and PI3K-Akt-mTOR signaling related proteins were measured by western blotting analysis. Results: CME (15-50 µg/mL) signiicantly inhibited the proliferation of CNE-1 in a dose- and time-dependent manner (P = 0.026 for 15 µg/mL, P < 0.001 for 25, 30, 40, and 50 µg/mL, respectively); the IC50 values (µg/mL) were 41.57 ± 0.17, 30.34 ± 0.06 and 24.98 ± 0.08 for 24, 48 and 72 h treatments, respectively. Signiicant morphological changes of CNE-1 cells displaying apoptosis were observed after CME treatment. CME showed low cytotoxicity toward normal LO2 cells. CNE-1 cells were arrested in the G2/M phase while treated with 15, 25, 40 µg/mL of CME, respectively (P = 0.032, P = 0.0053, P < 0.001). CME (15, 25, 40 µg/mL) down-regulated Bcl-2 expression (P = 0.032, P = 0.0074, P < 0.001), and up-regulated Bax (P = 0.026, P = 0.0056, P < 0.001) with activation of caspase-3, caspase-8, caspase-9, and PARP observed in CNE-1 cells (P = 0.015, P = 0.0067, P < 0.001 for caspase 3; P = 0.210, 0.028, < 0.001 for caspase 8; P = 0.152, 0.082, 0.0080 for caspase 9; P = 0.265, 0.0072, < 0.001 for PARP). CME suppressed the activation of the PI3K-AKT-mTOR pathway (P = 0.03, 0.0007, 0.004, 0.006, 0.022 for p-PI3K, p-Akt-Ser473, p-Akt-Thr308, p-mTOR-Ser2448, p-mTOR-Ser2481, respectively after 40 µg/mL of CME treated for 24 h). Conclusion: CME inhibited the proliferation of CNE-1 cells and activation of the PI3K-AKT-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Analytical formulations were derived for bifurcation pressure and non-linear static analysis of a corroded ring under external pressure. The mid-surface inextensional condition was included in the derivation which resulted in much improved accuracy in the prediction of bifurcation pressure. Afterwards, an analytical method was presented to solve the non-linear deformation problem of a corroded ring with initial ovality included under external pressure. A finite element analysis was carried out to verify the accuracy of the developed model. By setting the initial yielding as the failure criterion, a parametric study was carried out to study the effect of corrosion depth and corrosion angular extent. Moreover, the interaction effect of two circumferential corroded regions on the critical pressure was studied. Finally, some comments on the analytical methods were given to consider the case of continuously varying thickness and an alternative perturbative method was proposed. This research is intended to enhance the understanding of instability and failure for a corroded tube under external pressure mainly applicable to offshore industry. [ABSTRACT FROM AUTHOR]

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis. We divided IL-1Ra+/–/apolipoprotein-E (apoE)-/- and IL-1Ra+/+/apoE-/- mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and CRP were quantified in the 3 murine groups. At 16 weeks, plaque thickness in the ascending aortas of the IL-1Ra+/–/apoE-/- mice was significantly greater than that in the IL-1Ra+/+/apoE-/- mice, on ultrasound and histology (P <0.01). In contrast, at 32 weeks, the differences between these 2 genotypes were not statistically significant. Serum IL-1 levels were lower in the IL-1Ra+/–/apoE-/- mice than in the IL-1Ra+/+/apoE-/- mice at 16 and 32 weeks (P <0.05). At 16 weeks, serum CRP levels in the IL-1Ra+/–/apoE-/- mice were higher than in the IL-1Ra+/+/apoE-/- mice (P <0.01). Our results suggest that ultrasound biomicroscopy enables evaluation of atherosclerotic lesions in vivo, noninvasively and in real-time, in apoE-/- mice. Partial IL-1Ra deficiencies might promote early plaque development in 16-week-old apoE-/- mice. The balance of IL-1 and IL-1Ra might influence atherosclerotic development. Finally, CRP might affect the initiation of atherosclerosis, rather than its progression. [ABSTRACT FROM AUTHOR]

Background: Unplanned re-attendance at the Emergency Department (ED) is often monitored as a quality indicator of the care accorded to patients during their index ED visit. High bed occupancy rate (BOR) has been considered as a matter of reduced patient comfort and privacy. Most hospitals in Singapore operate under BORs above 85 %. This study aims to explore factors associated with the unplanned 3-day ED re-attendance rate and, in particular, if higher BOR is associated with higher 3-day unplanned ED re-attendance rate. Methods: This was a multicenter retrospective study using time series data. Three acute tertiary hospitals were selected from all six adult public hospitals in Singapore based on data availability. Daily data from year 2008 to 2013 were collected from the study hospitals' information systems. These included: ED visit date, day of week, month, year, public holiday, daily hospital BOR, daily bed waiting time (BWT) at ED (both median and 95th percentile), daily ED admission rate, and 3-day ED re-attendance rate. The primary outcome of the study was unplanned 3-day ED re-attendance rate from all reasons. Both univariate analysis and generalized linear regression were respectively applied to study the crude and adjusted association between the unplanned 3-day ED reattendance rate and its potential associated factors. All analyses were conducted using SPSS 18 (PASW 18, IBM). Results: The average age of patients who visited ED was 35 years old (SD = 2), 37 years old (SD = 2), and 40 years old (SD = 2) in hospitals A, B, and C respectively. The average 3-day unplanned ED re-attendance rate was 4.9 % (SE = 0.47 %) in hospital A, 3.9 % (SE = 0.35 %) in hospital B, and 4.4 % (SE = 0.30 %) in hospital C. After controlling for other covariates, the unplanned 3-day ED re-attendance rates were significantly associated with hospital, time trend, day of week, daily average BOR, and ED admission rate. Strong day-of-week effect on early ED re-attendance rate was first explored in this study. Thursday had the lowest re-attendance rate, while Sunday has the highest re-attendance rate. The patients who visited at ED on the dates with higher BOR were more likely to re-attend the ED within 3 days for hospitals A and B. There was no significant association between BOR and ED re-attendance rate in hospital C. Conclusions: A study using time series data has been conducted to explore the factors associated with the unplanned 3-day ED re-attendance rate. Strong day-of-week effect was first reported. The association between BOR and the ED re-attendance rate varied with hospital. [ABSTRACT FROM AUTHOR]

The existing heavy-backbone object detection models overlook the crucial role of cross-level interactive fusion of feature information in pyramid networks, resulting in the inability to detect occluded objects or small objects in complex scenes. In this thesis, we present a new heavy-neck object detection model called POD-YOLO based on YOLOv5s. Firstly, we propose the POD-RepC3 module to increase the model's capability to obtain the multi-layer feature. Additionally, addressing the issue of large object size span, we propose a bidirectional partial dynamic fusion module (Bi-PDC) as the detection neck of the pyramid network. This module preserves the accurate positioning signals and facilitates cross-level interactive fusion of feature information. Finally, we design Reparameterized Bi-directional Dynamic Feature Pyramid Network (RepBi-DFPN), a deep feature fusion network that integrates contextual information and enhances both feature expression and fusion capabilities of our model. The experiment results suggest that the suggested method is positive on the PASCAL VOC dataset. The mAP@0.5 and mAP@0.5:0.95 performance reached 81.3% and 58.2%, respectively, which increased by 2.4% and 4.1% compared to original algorithm YOLOv5s. Furthermore, experiment results also demonstrate that model's performance can compete with SOTA object detection models. In this paper, the algorithm optimizes the feature fusion capability of the pyramid network to effectively decrease the false detection and missing detection of the model. The model's ability to accurately detect multi-scale targets is significantly improved. [ABSTRACT FROM AUTHOR]

A method has been developed for the chemo- and stereoselective Suzuki-Miyaura cross-coupling of optically enriched gem-diboronyl compounds with various aryl bromides. Experimental evidence suggests that the Lewis acidity of the second boron group in these substrates plays a significant role in facilitating these otherwise challenging cross-coupling processes. β-Diboronyl esters may be successfully cross-coupled in excellent yield and enantiomeric excess with prior conversion of the pinacol boronate to the corresponding trifluoroborate salt. In contrast, a substrate bearing a Weinreb amide can undergo direct coupling of the Bpin moiety, likely due to the stronger coordination of the more basic amide carbonyl group. The resulting optically enriched secondary boronate may be used in a second enantioselective cross-coupling to afford pharmaceutically relevant diarylmethane products. The use of a Weinreb amide substrate allows for facile postcoupling modification, as demonstrated by a transformation to the corresponding ketone. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of study is to solve the multi-modal transportation routing planning problem that aims to select an optimal route to move a consignment of goods from its origin to its destination through the multi-modal transportation network. And the optimization is from two viewpoints including cost and time. Design/methodology/approach: In this study, a bi-objective mixed integer linear programming model is proposed to optimize the multi-modal transportation routing planning problem. Minimizing the total transportation cost and the total transportation time are set as the optimization objectives of the model. In order to balance the benefit between the two objectives, Pareto optimality is utilized to solve the model by gaining its Pareto frontier. The Pareto frontier of the model can provide the multi-modal transportation operator (MTO) and customers with better decision support and it is gained by the normalized normal constraint method. Then, an experimental case study is designed to verify the feasibility of the model and Pareto optimality by using the mathematical programming software Lingo. Finally, the sensitivity analysis of the demand and supply in the multi-modal transportation organization is performed based on the designed case. Findings: The calculation results indicate that the proposed model and Pareto optimality have good performance in dealing with the bi-objective optimization. The sensitivity analysis also shows the influence of the variation of the demand and supply on the multi-modal transportation organization clearly. Therefore, this method can be further promoted to the practice. Originality/value: A bi-objective mixed integer linear programming model is proposed to optimize the multi-modal transportation routing planning problem. The Pareto frontier based sensitivity analysis of the demand and supply in the multi-modal transportation organization is performed based on the designed case. [ABSTRACT FROM AUTHOR]

Cervical cancer is the third most common malignancy worldwide, accounting for 250,000 mortalities annually. Notch1, an important regulator of cell-fate decisions and differentiation, has been found to be overexpressed in certain types of cancer. However, the role of Notch1 in cervical carcinogenesis remains unclear. In the present study, immunohistochemical staining and western blot analysis revealed that Notch1 expression was significantly higher in cervical cancer tissues than that in normal cervical tissues. Furthermore, statistical analysis revealed that Notch1 expression was significantly associated with tumor differentiation and tumor stage. These findings indicated that Notch1 expression was associated with the progression of cervical cancer. The western blot assay also identified a positive correlation between Notch1 and Ki67 expression in cervical cancer tissues, which suggested that Notch1 expression may be associated with the proliferation of cervical cancer. In order to further evaluate the specific role of Notch1 in cervical cancer progression, its expression in SiHa and C33A cells was knocked down using small interfering RNA. It was revealed that the knockdown of Notch1 in SiHa and C33A cells resulted in significant inhibition of cell proliferation and colony formation in vitro. These results indicated that Notch1 was able to promote cell proliferation in cervical cancer. In conclusion, the results of the present study indicated that Notch1 may function as a promoter in cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in the brain, and is predominantly expressed in astrocytes, but at lower levels also in excitatory terminals. We generated a conditional GLT-1 knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation of the GLT-1 gene was achieved in either neurons or astrocytes by expression of synapsin-Cre or inducible human GFAPCreERT2. Elimination of GLT-1 from astrocytes resulted in loss of ~80% of GLT-1 protein and of glutamate uptake activity that could be solubilized and reconstituted in liposomes. This loss was accompanied by excess mortality, lower body weight, and seizures suggesting that astrocytic GLT-1 is of major importance. However, there was only a small (15%) reduction that did not reach significance of glutamate uptake into crude forebrain synaptosomes. In contrast, when GLT-1 was deleted in neurons, both the GLT-1 protein and glutamate uptake activity that could be solubilized and reconstituted in liposomes were virtually unaffected. These mice showed normal survival, weight gain, and no seizures. However, the synaptosomal glutamate uptake capacity (Vmax) was reduced significantly (40%). In conclusion, astrocytic GLT-1 performs critical functions required for normal weight gain, resistance to epilepsy, and survival. However, the contribution of astrocytic GLT-1 to glutamate uptake into synaptosomes is less than expected, and the contribution of neuronal GLT-1 to synaptosomal glutamate uptake is greater than expected based on their relative protein expression. These results have important implications for the interpretation of the many previous studies assessing glutamate uptake capacity by measuring synaptosomal uptake. [ABSTRACT FROM AUTHOR]

Attributive recognition model of coalmining-based cities ecosystem classification is developed in terms of attributive mathematical theory. Based on the analysis of main causes of coalmining-based cities ecosystem, the city vitality, city structure strength, city resilience ability, service functions and health status are chosen as the criterion indicators of coalmining-based cities ecosystem classification; the attributive measurement functions are constructed to compute the attributive measurement of single indicator and multi-indicator; and the synthetic attributive measurement is calculated by the AHP; the health classification of cities ecosystem are recognized by the confidence criterion. An empirical analysis is made by the proposed model and method, the synthetic evaluation results are better than fuzzy comprehensive evaluation method which validates the proposed model feasible, effective and reliable in coalmining-based cities ecosystem classification. As attributive recognition theory can success fully resolve certain issues with a number of fuzzy attribution in comprehensive evaluation, its confidence criterion is established on the basis of the ordered evaluation sets, consequently it will make the evaluation results more reliable. [ABSTRACT FROM AUTHOR]

Using a monotone iterative method combined with some inequalities associated with the Green's function, we investigate the existence of positive solutions for a fractional differential equation with integral boundary conditions. In addition, two examples are given to illustrate the results. [ABSTRACT FROM AUTHOR]

Background: The clinical and prognostic significance of C-reactive protein (CRP) in nonsmall-cell lung cancer (NSCLC) remains inconsistent. To clarify a precise determinant of the clinical significance of CRP, we conducted a systematic review and meta-analysis to evaluate the overall risk of elevated CRP for survival in NSCLC. Materials and Methods: Related studies were identified and evaluated for quality through multiple search strategies. Data were collected from studies comparing overall survival in patients with elevated CRP levels and those having lower levels. The meta-analysis was performed by Review Manager version 5.2 (RevMan; the Cochrane Collaboration, Oxford, England). The pooled hazard ratios (HRs) and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight eligible studies involved 1649 patients were ultimately identified. Combined HRs suggested that elevated CRP had an unfavorable impact on survival of patients with NSCLC. The HRs (95% CI) was 1.55 (1.19-2.01) overall, 1.78 (1.33-2.38) in Asian patients, 1.33 (1.00-1.77) in non-Asian patients, 1.78 (1.47-2.15) in primary resectable NSCLC, 1.28 (0.95-1.73) in primary unresectable NSCLC, 1.78 (1.33-2.38) in group of cut-off value <5 mg/L, 1.33 (1.00-1.77) in group of cut-off value >10 mg/L. onclusions: With the available evidence, CRP might serve as an efficient prognostic indicator in NSCLC. This marker should be taken into consideration in the development of new diagnostic and therapeutic program for NSCLC. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p = 0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p = 0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p > 0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study. [ABSTRACT FROM AUTHOR]

Isolated torsion of a fallopian tube in the third trimester of pregnancy is an uncommon event. Its common symptoms are lower abdominal pain, vomiting, and nausea. Because these symptoms are nonspecific, isolated torsion of a fallopian tube may be misdiagnosed, delaying treatment and the opportunity to preserve the tube. This is a case report of a primipara in her third trimester, who was misdiagnosed as having acute appendicitis and ovarian cyst torsion. The ultrasound-assisted examination was useful, but the specific diagnosis was made after laparotomy and histopathology. The patient was managed by simultaneous salpingectomy and cesarean section. This surgical intervention prevented adverse obstetric sequelae. We summarize our experience, provide our conclusions, and review 17 relevant studies from the literature to aid clinicians in understanding, diagnosing, and managing this condition in a timely fashion. [ABSTRACT FROM AUTHOR]

A new replacement name is proposed for the species Tropidocephala speciosa Ding, 2006 (Hemiptera: Fulgoromorpha: Delphacidae: Tropidocephalini), preoccupied by Tropidocephala speciosa (Bierman, 1908): Tropidocephala dingi Sun, Yang & Chen, nom. n. = Tropidocephala speciosa Ding, 2006. The photographs and illustrations of this species are also provided. [ABSTRACT FROM AUTHOR]

Background Most nemerteans (phylum Nemertea) are free-living, but about 50 species are known to be firmly associated with other marine invertebrates. For example, Gononemertes parasita is associated with ascidians, and Nemertopsis tetraclitophila with barnacles. There are 12 complete or near-complete mitochondrial genome (mitogenome) sequences of nemerteans available in GenBank, but no mitogenomes of none free-living nemerteans have been determined so far. In the present paper complete mitogenomes of the above two parasitic/commensal nemerteans are reported. Methods The complete mitochondrial genomes (mitogenome) of G. parasita and N. tetraclitophila were amplified by conventional and long PCR. Phylogenetic analyses of maximum likelihood (ML) and Bayesian inference (BI) were performed with both concatenated nucleotide and amino acid sequences. Results Complete mitogenomes of G. parasita and N. tetraclitophila are 14742 bp and 14597 bp in size, respectively, which are within the range of published Hoplonemertea mitogenomes. Their gene orders are identical to that of published Hoplonemertea mitogenomes, but different from those of Palaeo- and Heteronemertea species. All the coding genes, as well as major non-coding regions (mNCRs), are AT rich, which is especially pronounced at the third codon position. The AT/GC skew pattern of the coding strand is the same among nemertean mitogenomes, but is variable in the mNCRs. Some slight differences are found between mitogenomes of the present species and other hoplonemerteans: in G. parasita the mNCR is biased toward T and C (contrary to other hoplonemerteans) and the rrnS gene has a unique 58-bp insertion at the 5' end; in N. tetraclitophila the nad3 gene starts with the ATT codon (ATG in other hoplonemerteans). Phylogenetic analyses of the nucleotide and amino acid datasets show early divergent positions of G. parasita and N. tetraclitophila within the analyzed Distromatonemertea species, and provide strong support for the close relationship between Hoplonemertea and Heteronemertea. Conclusion Gene order is highly conserved within the order Monostilifera, particularly within the Distromatonemertea, and the special lifestyle of G. parasita and N. tetraclitophila does not bring significant variations to the overall structures of their mitogenomes in comparison with free-living hoplonemerteans. [ABSTRACT FROM AUTHOR]

Background: Cytochrome P450 (CYP) 2C19 is a very important drug metabolizing enzyme. Although the single nucleotide polymorphisms (SNPs) of CYP2C19 G681A and G636A have been suggested that they may increase the incidence of cardiovascular events, the relationship between SNPs in CYP2C19 and cerebral ischemic stroke (CIS) are unclear. The aim of this study was to investigate the correlation between the distribution of G681A and G636A polymorphisms in CYP2C19 gene and the risk of CIS in Chinese. Methods: The peripheral blood DNA was extracted from 299 patients with CIS and 295 healthy controls. The genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism. The sampled sequencing was applied to verify the correctness of genotyping results. Both the genotype and allele distributions were compared in patients with CIS and healthy controls. Results: The frequencies of CYP2C19 681AA (11.7% vs. 2.7%; P = 0.000), 636AA (4.0% vs. 0.7%; P = 0.007), 636AG (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (30.9% vs. 20.8%; P = 0.000) and 636A (13.0% vs. 5.8%; P = 0.000) allele in the CIS group are significantly higher than those in the controls. The frequencies of CYP2C19 681AA (16.7% vs. 8.6%; P = 0.036), CYP2C19 636AA (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (36.4% vs. 27.6%; P = 0.023) and CYP2C19 636A (17.5% vs.10.3%; P = 0.010) allele in the recurrent stroke group are significantly higher than those in the first onset group. Multivariate logistic regression analysis of risk factors for cerebral ischemic stroke and recurrent stroke respectively suggests that the CYP2C19 681AA genotype may be an independent risk factor for CIS (OR = 6.179, 95% CI: 2.285 ~ 16.708; P = 0.000) and recurrent stroke (OR = 2.305, 95% CI: 1.121 ~ 4.743; P = 0.023). Conclusions: The AA genotype and A allele of CYP2C19 G681A may be related to the occurrence and recurrence of cerebral ischemic stroke. [ABSTRACT FROM AUTHOR]

Solitary metastatic renal tumors are rarely encountered. We report the case of a 63-year-old man who developed a solitary renal metastasis after undergoing an esophagectomy for esophageal squamous cell carcinoma and subsequent nephrectomy of the right kidney. [ABSTRACT FROM AUTHOR]

Background A new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) has recently been published. This study aimed to investigate the utility of the new histological classification for identifying the prognostic subtypes of adenocarcinomas in stage IB patients.Correlations between the classification and the presence of epidermal growth factor receptor (EGFR) mutation status was also studied. Methods One hundred and thirty-six patients with stage IB lung adenocarcinoma operated on in Zhejiang Cancer Hospital were identified between 2002 and 2011. Patients overall survival and disease-free survival were calculated using Kaplan-Meier and Cox regression analyses. EGFR mutations were detected using the amplification refractory mutation system. Results A total of 136 cases were included in current study, of which 38 were papillary predominant, 39 were acinar predominant, 22 were micropapillary predominant, 21 were lepidic predominant subtypes, 14 were solid predominant, and 2 were variants of invasive adenocarcinoma. Patients with micropapillary- and solid-predominant tumors had the lowest five-year disease-free survival (28.4 and 36.7%, respectively). Univariate and multivariate analysis showed that the micropapillary-predominant subtype was an independent predictor of disease-free survival (P = 0.0041 and 0.048, respectively), but not overall survival (P = 0.175 and 0.214, respectively). EGFR mutations were significantly associated with the micropapillary-predominant subtype patients (P = 0.0026). The EGFR mutation frequency is lower in the solid-predominant subtype than other subtypes (P = 0.0508). Conclusions The predominant subtype in the primary tumor was associated with prognosis in resected stage IB lung adenocarcinoma. The EGFR mutation frequency of micropapillarypredominant subtype is higher than other subtypes. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aim to design a mathematical model for railway freight volume prediction which can provide an accurate direction for railway freight resource allocation. Based on the precise prediction, railway freight enterprises are able to optimize and integrate the limited resources to organize freight transport more efficiently and economically. Design/methodology/approach: In this study, we design a PSO-GRNN model to predict railway freight volume. In the proposed model, GRNN carries out the nonlinear regression analysis between railway freight volume and its influencing factors which can be described by detailed and measurable indexes and outputs the prediction value. PSO algorithm with time linear decreasing inertia weight and time varying acceleration coefficients is applied to optimize the basic GRNN model by searching the optimal smoothing parameter. Findings: The simulation result in this study indicates that (1) the PSO-GRNN model is able to predict railway freight volume by using the value of other relevant indexes as its input to fit the variation of railway freight volume; (2) Through optimization for GRNN model based on PSO algorithm, the proposed model performs well prediction accuracy; (3) Compared with RBFNN model and BPNN model, the superiority of the proposed model in prediction accuracy and curve fitting capacity is verified. Originality/value: In the empirical study from China, we establish a railway freight volume prediction index system containing seventeen prediction indexes from five influencing factors. Then we construct the PSO-GRNN model to predict the railway freight volume from 2007 to 2011 by using data from 1990 to 2006 as training samples. In order to verify the feasibility and prediction accuracy of the proposed model, we also use two widely applied neural network models, including RBFNN model and BPNN model, to estimate the railway freight volume prediction during the same period. Compared with RBFNN model and BPNN model, the simulation results indicate that the proposed model has higher prediction accuracy and better curve fitting capacity. Therefore, PSO-GRNN model can be further applied in practical railway freight production. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that miRNA regulatory circuits play important roles in tumorigenesis. We previously reported that miR-124 is correlated with prognosis of colorectal cancer due to PKM-dependent regulation of glycolysis. However, the mechanism by which miR-124 regulates apoptosis in colorectal cancer remains largely elusive. Here, we show that miR-124 induced significant apoptosis in a panel of colorectal cancer cell lines. The mitochondrial apoptosis pathway was activated by miR-124. Furthermore, the pro-apoptotic role of miR-124 was dependent on the status of PKM1/2 level. PKM1 was required for miR-124-induced apoptosis. Via direct protein-protein interaction, PKM1 promoted HNF4a binding to the promoter region of miR-124 and transcribing miR-124. Moreover, HNF4a or PKM1 had a more dramatic effect on colorectal cancer cell apoptosis in the presence of miR-124. However, inhibition of miR-124 blocked cell apoptosis induced by HNF4a or PKM1. These data indicate that miR-124 not only alters the expression of genes involved in glucose metabolism but also stimulates cancer cell apoptosis. In addition, the positive feedback loop between miR-124 and PKM1/HNF4a plays an important role in colorectal cancer cell apoptosis; it suggests that disrupting this regulatory circuit might be a potential therapeutic tool for colorectal cancer treatment. [ABSTRACT FROM AUTHOR]

We present the results of a 6.7 GHz methanol maser survey from the Effelsberg 100 m radio telescope. A sample of 404 sources from the Bolocam Galactic Plane Survey (BGPS) 1.1 mm dust clump survey that met specific Galactic Legacy Infrared Mid-Plane Survey Extraodinaire (GLIMPSE) point-source color criteria was selected and 318 of these were observed. The new observations resulted in the detection of 29 methanol masers, including 12 new ones. Together with the additional 74 detections from the literature, this means that a total of 103 methanol masers are coincident with 1.1 mm dust clumps, yielding an overall detection rate of 26%. A comparison of the properties of a 1.1 mm dust clump and a 6.7 GHz methanol maser indicates that methanol masers with a higher flux density and/or luminosity are generally associated with more massive but less dense 1.1 mm dust clumps. The overall detection rate of 26% appears to vary as a function of the derived H2 column density of the associated 1.1 mm dust clump. The methanol masers were primarily detected toward the brighter and more massive 1.1 mm dust clumps. A subsample of 194 sources that overlapped sources with observations of the 95 GHz methanol line was investigated in more detail for the properties of 1.1 mm dust clumps. The statistical analysis reveals that 1.1 mm dust clumps with both class I and II counterparts have much higher mean and median values of mass, column density, and flux density than those with only class I or II counterparts. Based on our much larger sample, we slightly revise the boundary defined previously for selecting BGPS sources associated with a class II methanol maser, wherein -80% of expected class II methanol masers will be detected with a detection rate in the range of 40-50%. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a key process in the tumor metastatic cascade that is characterized by the loss of cell-cell junctions and cell polarity, resulting in the acquisition of migratory and invasive properties. Recent evidence showed that altered microRNA-10b (miR-10b) expression was implicated in the occurrence of EMT of breast cancer. However, the exact role and underlying mechanisms of miR-10b in the EMT of breast cancer still remain unknown. In this study, miR-10b was found to be upregulated in breast cancer tissues and breast cancer cell lines and the expression of miR-10b was shown to be closely correlated with aggressiveness in breast cancer. Treating breast cancer cells with the miR-10b inhibitor increased E-cadherin expression while decreasing vimentin expression. At the same time, on inhibition of miR-10b, the invasion and proliferation ability of breast cancer cells also decreased. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces EMT in multiple cell types. Here, we identified miR-10b as a target gene of TGF-β1. The expression of miR-10b increased during TGF-β1-induced EMT of breast cancer cells. Further study showed that inhibition of miR-10b expression partially reversed the EMT, invasion and proliferation induced by TGF-β1 in breast cancer cells. Taken together, these results demonstrated a novel function for miR-10b in TGF-β1-induced EMT in breast cancer and increased their metastatic potential. MiR-10b might become a possible target for gene therapy in breast cancer. [ABSTRACT FROM AUTHOR]

High atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) contents in the environment threaten the health conditions of organisms. We examined the effects of ATR exposure on Sprague-Dawley rats during gestation and on the dopaminergic neurons of offspring during lactation. Pregnant dams were orally treated with 0 mg/kg/day to 50 mg/kg/day of ATR from gestational day 5 to postnatal day 22. Afterward, neither offspring nor dams received ATR. Dopamine (DA) content was examined in striatum samples by HPLC-FL; the mRNA expressions of tyrosine hydroxylase (TH), orphan nuclear hormone (Nurr1), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) in the ventral midbrain samples were examined by fluorescence PCR when the offspring reached one year of age. After the pregnant rats were exposed to ATR, the DA concentrations and mRNA levels of Nurr1 were decreased in their offspring. Decreased Nurr1 levels were also accompanied by changes in the mRNA levels of VMAT2, which controls the transport and reuptake of DA. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine (TCM) is explained in the language of engineering cybernetics (EC), an engineering science with the tradition of rigor and long history of practice. The inherent connection is articulated between EC, as a science of interrelations, and the Chinese conception of Wuxing. The combined cybernetic model of Wuxing seems to have significant explaining power for the TCM and could potentially facilitate better communications of the insights of the TCM to the West. In disturbance rejection, an engineering concept, a great metaphor, is found to show how the TCM is practiced, using the liver cancer pathogenesis and treatment as a case study. The results from a series of experimental studies seem to lend support to the cybernetic model of Wuxing and the principles of disturbance rejection. [ABSTRACT FROM AUTHOR]

Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) is a viral endoribonuclease with an unknown function. The regulation of cellular gene expression by nsp11 was examined by RNA microarrays using MARCnsp11 cells constitutively expressing nsp11. In these cells, the interferon-β, interferon regulatory factor 3, and nuclear factor-κB activities were suppressed compared to those of parental cells, suggesting that nsp11 might serve as a viral interferon antagonist. Differential cellular transcriptome was examined using Affymetrix exon chips representing 28,536 transcripts, and after statistical analyses 66 cellular genes were shown to be upregulated and 104 genes were downregulated by nsp11. These genes were grouped into 5 major signaling pathways according to their functional relations: histone-related, cell cycle and DNA replication, mitogen activated protein kinase signaling, complement, and ubiquitin-proteasome pathways. Of these, the modulation of cell cycle by nsp11 was further investigated sincemany of the regulated genes fell in this particular pathway. Flow cytometry showed that nsp11 caused the delay of cell cycle progression at the S phase and the BrdU staining confirmed the cell cycle arrest in nsp11-expressing cells. The study provides insights into the understanding of specific cellular responses to nsp11 during PRRSV infection. [ABSTRACT FROM AUTHOR]

We study the existence and uniqueness of positive solutions for a class of singular m-point boundary value problems of second order differential equations on a measure chain. A sharper sufficient condition for the existence and uniqueness of Crd¹[0, T] positive solutions as well as Crd¹[0, T] positive solutions is obtained by the technique of lower and upper solutions and the maximal principle theorem. [ABSTRACT FROM AUTHOR]

It is crucial to ascertain the comprehensive influence factors on personality for making effective cultivating plan. However, most existing literatures focus on the effect of individual factor on the personality. In order to comprehensively investigate the causal influences of preschool children's temperament, school factors (teacher expectation and peer acceptance), and family factors (parental coparenting style, parental education value, and parental parenting style) on the personality and the probability of the dependencies among these influence factors, we constructed the influencing factor model of personality development based on the Bayesian network. The models not only reflect the influence on personality development as a whole, but also obtain the probability relationships among the factors. Compared with other influence factors including family and school factors, temperament has more effect on the personality. In addition, teacher expectation also has an important influence on the personality. The experimental results show that it is a valuable exploration to construct the Bayesian network for comprehensively investigating the causal relationships between preschool children's personality and related influence factors. Further, these results will be helpful to the cultivation of healthy personality. [ABSTRACT FROM AUTHOR]

Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4R in leptin receptor mutant (Leprdb/db) females result in restoration of fertility and lactation despite the persistence of obesity and insulin resistance. The overarching hypothesis in the present study is that the absence or reduction of leptin's inhibition of AGRP/NPY neurons leads to suppression of GnRH release in cases of leptin signaling deficiency. Since TAC2 (NKB)-TAC3R signaling plays a role in puberty maturation and is modulated by metabolic status, the other aim of this study is to test whether TAC2/NKB neurons in ARC regulated by melanocortinergic signals herein affect leptin's action on puberty and reproduction. Our data showed that AGRP deficiency in Leprdb/db females restores normal timing of vaginal opening and estrous cycling, although uterine weight gain and mammary gland development are morphologically delayed. Nonetheless, Agrp-/- Leprdb/db females are fertile and sustain adequate nutrition of pups with lactation to weaning age. AGRP deficiency results in advanced vaginal opening in wild-type female mice. The postpubertal increase in hypothalamic TAC2 mRNA was not observed in Leprdb/db females, whereas AGRP deficiency restored it in Leprdb/db females. Additionally, MC4R activation with MTII induced FOS expression in TAC2 neurons, supporting the concept of melanocortinergic regulation of TAC2 neurons. These studies suggest that AGRP imposes an inhibitory effect on puberty and that TAC2 neurons may transmit melanocortinergic inhibition of GnRH neurons. [ABSTRACT FROM AUTHOR]

In this study, a rapid and simple method which combines drop coating deposition and Raman spectroscopy (DCDR) was developed to characterize the dry embryo culture media (ECM) droplet. We demonstrated that Raman spectra obtained from the droplet edge presented useful and characteristic signatures for protein and amino acids assessment. Using a different analytical method, scanning electron microscopy coupled with energy dispersive X-ray analysis, we further confirmed that Na, K, and Cl were mainly detected in the central area of the dry ECM droplet while sulphur, an indicative of the presence of macromolecules such as proteins, was mainly found at the periphery of the droplet. In addition, to reduce sample preparation time, different temperatures for drying the droplets were tested. The results showed that drying temperature at 50°C can effectively reduce the sample preparation time to 6 min (as compared to 50 min for drying at room temperature, ~25°C) without inducing thermal damage to the proteins. This work demonstrated that DCDR has potential for rapid and reliable metabolomic profiling of ECM in clinical applications. [ABSTRACT FROM AUTHOR]

One transcription factor mediator of Ca2+-signals is cAMP response element-binding protein (CREB). CREB expression and/or activity negatively correlates with vascular smooth muscle (VSM) cell proliferation and migration. Multifunctional Ca2+/calmodulin-dependent protein kinases, including CaMKII, have been demonstrated to regulate CREB activity through both positive and negative phosphorylation events in vitro, but the function of CaMKII as a proximal regulator of CREB in intact cell systems, including VSM, is not clear. In this study, we used gain- and loss-of-function approaches to determine the function of CaMKIIδ in regulating CREB phosphorylation, localization, and activity in VSM. Overexpression of constitutively active CaMKIIδ specifically increased CREB phosphorylation on Ser142 and silencing CaMKIIδ expression by siRNA or blocking endogenous CaMKII activity with KN93 abolished thrombin- or ionomycin-induced CREB phosphorylation on Ser142 without affecting Ser133 phosphorylation. CREB-Ser142 phosphorylation correlated with transient nucleocyto-plasmic translocation of CREB. Thrombin-induced CREB promoter activity, CREB binding to Sik1 and Rgs2 promoters, and Sik1/Rgs2 transcription were enhanced by a kinase-negative CaMKIIδ2 (K43A) mutant and inhibited by a constitutively active (T287D) mutant. Taken together, these studies establish negative regulation of CREB activity by endogenous CaMKIIδ-dependent CREB-Ser142 phosphorylation and suggest a potential mechanism for CaMKIIδ/CREB signaling in modulating proliferation and migration in VSM cells. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion injury (IRI) occurs frequently during reperfusion of ischemic myocardium, and preconditioning has been regarded as one of the best strategies to prevent myocardial injury during the ischemia/reperfusion process. Our previous studies indicated that a small dose of sulfur dioxide (SO2) used as preconditioning exerts cardioprotection. However, the mechanisms underlying the cardioprotection remain unclear. The present study was designed to examine if the extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway mediated protection against cardiac dysfunction after SO2 preconditioning in isolated rat hearts subjected to ischemia/reperfusion (I/R). Langendorff heart perfusion was performed in vitro, where 56 male Wistar rats were randomly divided into seven groups: control group, 5 µmol/L SO2 group (S5), 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) + 5 µmol/L SO2 (PD98059 + S5) group, PD98059 group, I/R group, 5 µmol/L SO2 + I/R (S5 + I/R) group and PD98059 + 5 µmol/L SO2 + I/R (PD98059 + S5 + I/R) group. Cardiac function and myocardial phosphorylated ERK1/2 protein were measured. We found that I/R in isolated rat heart resulted in cardiac dysfunction with a significant increase in phosphorylated ERK1/2 protein. SO2 preconditioning markedly suppressed phosphorylated ERK1/2 protein and improved cardiac function in isolated rat heart with I/R (p < 0.05). However, pre-treatment with PD98059 could prevent the above effects of SO2 preconditioning. In conclusion, SO2 preconditioning protected against cardiac dysfunction in isolated rat heart subjected to I/R via suppression of the over-activation of the ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

Cells use complex mechanisms to regulate glucose transport and metabolism to achieve optimal energy and biomass production while avoiding accumulation of toxic metabolites. Glucose transport and glycolytic metabolism carry the risk of the buildup of phosphosugars, which can inhibit growth at high concentrations. Many enteric bacteria cope with phosphosugar accumulation and associated stress (i.e., sugar-phosphate stress) by producing a small RNA (sRNA) regulator, SgrS, which decreases phosphosugar accumulation in part by repressing translation of sugar transporter mRNAs (ptsG and manXYZ) and enhancing translation of a sugar phosphatase mRNA (yigL). Despite a molecular understanding of individual target regulation by SgrS, previously little was known about how coordinated regulation of these multiple targets contributes to the rescue of cell growth during sugar-phosphate stress. This study examines how SgrS regulation of different targets impacts growth under different nutritional conditions when sugar-phosphate stress is induced. The severity of stress-associated growth inhibition depended on nutrient availability. Stress in nutrient-rich media necessitated SgrS regulation of only sugar transporter mRNAs (ptsG or manXYZ). However, repression of transporter mRNAs was insufficient for growth rescue during stress in nutrient-poor media; here SgrS regulation of the phosphatase (yigL) and as-yet-undefined targets also contributed to growth rescue. The results of this study imply that regulation of only a subset of an sRNA's targets may be important in a given environment. Further, the results suggest that SgrS and perhaps other sRNAs are flexible regulators that modulate expression of multigene regulons to allow cells to adapt to an array of stress conditions. [ABSTRACT FROM AUTHOR]

Background: Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study. Methods: A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk. Results: Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke patients. Conclusions: Five year post-stroke survival and rehospitalization due to stroke recurrence as well as their associations with patient demographics were studied for different stroke types in Singapore. Specific preventive strategies are needed to target the high risk groups to improve their long-term outcomes after acute stroke. [ABSTRACT FROM AUTHOR]

Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca2+]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca2+]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca2+]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca2+]i rise decreased in OAB and NB BUC to 43.40 ± 6.45 and 38.82 ± 3.5%, respectively. OXO tended to increase ACh release by OAB vs. NB BUC (9.02 ± 0.1 vs. 7.04 ± 0.09 μM, respectively; P < 0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated twofold in OAB BUC. OXO evoked greater increase in [Ca2+]i and ACh release in OAB BUC, although these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC. [ABSTRACT FROM AUTHOR]

The importance of genetic factors in substance addiction has long been established. The rationale for this work is that understanding of the function of addiction genes and delineation of the key molecular pathways of these genes would enhance the development of novel therapeutic targets and biomarkers that could be used in the prevention and management of substance abuse. Over the past few years, there has been a substantial increase in the number of genetic studies conducted on addiction in China; these studies have primarily focused on heroin, alcohol, and nicotine dependence. Most studies of candidate genes have concentrated on the dopamine, opioid, and serotonin systems. A number of genes associated with substance abuse in Caucasians are also risk factors in Chinese, but several novel genes and genetic risk factors associated with substance abuse in Chinese subjects have also been identified. This paper reviews the genetic studies of substance abuse performed by Chinese researchers. Genotypes and alleles related to addictive behavior in Chinese individuals are discussed and the contributions of Chinese researchers to the international corpus of knowledge about the genetic understanding of substance abuse are described. [ABSTRACT FROM AUTHOR]

T2DM is complex in its dynamical dependence on multiple tissues, disease states, and factors' interactions. However, most existing work devoted to characterizing its pathophysiology from one static tissue, individual factors, or single state. Here we perform a spatio-temporal analysis onT2DMby developing a new form of molecular network, i.e. 'differential expression network' (DEN), which can reflect phenotype differences at network level. Static DENs show that three tissues (white adipose, skeletal muscle, and liver) all suffer from severe inflammation and perturbed metabolism, among which metabolic functions are seriously affected in liver. Dynamical analysis on DENs reveals metabolic function changes in adipose and liver are consistent with insulin resistance (IR) deterioration. Close investigation on IR pathway identifies 'disease interactions', revealing that IR deterioration is earlier than that on SlC2A4 in adipose and muscle. Our analysis also provides evidence that rising of insulin secretion is the root cause of IR in diabetes [ABSTRACT FROM AUTHOR]

New treatment strategies are required for renal cell carcinoma (RCC) due to its relative insensitivity to conventional radio- and chemotherapies. The promising strategy of tumor inhibition using human telomerase reverse transcriptase (hTERT)-controlled herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) in the hTERT promoter-driven HSV-TK/GCV suicide gene system was investigated. Tumor volume, weight, relative proliferation rate, and cell-apoptosis levels were examined in mice injected with adenovirus (Ad)-hTERT-HSV-TK and GCV. Increased cell death occurred following treatment with Ads carrying hTERT-HSV-TK/GCV or cytomegalovirus promoter-controlled (CMV)-HSV-TK/GCV for human RCC 786-0 and fibroblast MRC-5 cells. In mice, Ad-hTERT-HSV-TK/GCV more specifically inhibited tumor and RCC xenograft growth than Ad-CMV-HSV-TK/GCV (P < 0.05). Furthermore, Ad-hTERT-HSV-TK/GCV did not significantly damage normal fibroblasts or organ systems (heart, lung, liver, brain, kidney, and spleen). Thus, Ad-hTERT-HSV-TK/GCV is an effective RCC inhibitor in human cells in vitro and in vivo mouse models, indicating potential usefulness in RCC-targeted gene therapy. [ABSTRACT FROM AUTHOR]

In wireless sensor networks (WSNs), periodical sleeping scheme on sensor nodes is an effective way to save energy. However, it will hinder the capability of the network to provide real-time data reporting due to relay node being sleep. Motivated by this, we propose an adaptive scheduling and routing scheme for guaranteeing dynamic end-to-end delay requirement while minimizing the energy consumption. First of all, we utilize an optimal wake-up scheduling algorithm to achieve the initial wake-up schedules and routes and design an adaptive adjustment algorithm. When the end-to-end delay requirement of a region changes, our proposed adaptive adjustment algorithm can locally adjust the wake-up schedules or the routing tables of the nodes which are the nearest ones to the source node, so as to minimize energy consumption and the impact on other regions while guaranteeing the new end-to-end delay requirement of the region. Through experiments in a real wireless sensor network and extensive simulations, we can get that the proposed scheme can conserve at least 20% energy consumption comparing to other existing adjustment algorithms, and its performance approaches that of the optimal solution. [ABSTRACT FROM AUTHOR]

Crocin is a carotenoid of the saffron extract that exhibits antitumor activity against many human tumors. However, the effects of crocin on HL-60 cells in vivo have not been evaluated. This study aimed to examine the effects of crocin on HL-60 cells in vitro and in vivo and investigate the underlying mechanisms. HL-60 cells were treated by crocin, and cell proliferation, apoptosis, and cell cycle profiles were examined by MTT assay, AO/EB staining, and flow cytometry, respectively. Furthermore, HL-60 cells were xenografted into nude mice and treated by crocin, the tumor weight and size were calculated, and the expression of Bcl-2 and Bax in xenografts was detected by immunohistochemical staining. The results showed that crocin (0.625-5 mg/mL) inhibited HL-60 cell proliferation and induced apoptosis and cell cycle arrest at G0/G1 phase, in a concentration and time-dependent manner. In addition, crocin (6.25,25 mg/kg) inhibited the tumor weight and size of HL-60 xenografts in nude mice, inhibited Bcl-2 expression, and increased Bax expression in xenografts. In summary, crocin inhibits the proliferation and tumorigenicity of HL-60 cells, which may be mediated by the induction of apoptosis and cell cycle arrest and the regulation of Bcl-2 and Bax expression. [ABSTRACT FROM AUTHOR]

The authors establish some new inequalities of P'olya type for multiple integrals on the n-dimensional ellipsoid, spherical shell, and ball, in terms of bounds of the higher order derivatives of the integrands. These results generalize the main result in the paper by Feng Qi, Inequalities for a multiple integral, Acta Mathematica Hungarica (1999). [ABSTRACT FROM AUTHOR]

We establish some new existence theorems on the positive solutions for nonlinear integro-differential equations which do not possess any monotone properties in ordered Banach spaces by means of Banach contraction mapping principle and cone theory based on some new comparison results. [ABSTRACT FROM AUTHOR]

The Wu-Huberman clustering is a typical linear algorithm among many clustering algorithms, which illustrates data points relationship as an artificial "circuit" and then applies the Kirchhoff equations to get the voltage value on the complex circuit. However, the performance of the algorithm is crucially dependent on the selection of pole points. In this paper, we present a novel pole point selection strategy for theWu-Huberman algorithm (named asPSWH algorithm), which aims at preserving the merit and increasing the robustness of the algorithm. The pole point selection strategy is proposed to filter the pole point by introducing sparse rate. Experiments results demonstrate that the PSWH algorithm is significantly improved in clustering accuracy and efficiency compared with the originalWu-Huberman algorithm. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) was recently identified as a factor produced by multiple myeloma (MM) cells, which may contribute to bone resorption and disease progression in MM, though the molecular mechanism of this process is not well understood. The purpose of this study was to test the effect of BDNF on bone disease and growth of MM cells both in vitro and in vivo. Co- and triple-culture systems were implemented. The in vitro results demonstrate that BDNF augmented receptor activator of nuclear factor kappa B ligand (RANKL) expression in human bone marrow stromal cells, thus contributing to osteoclast formation. To further clarify the effect of BDNF on myeloma bone disease in vivo, ARH-77 cells were stably transfected with an antisense construct to BDNF (AS-ARH) or empty vector (EV-ARH) to test their capacity to induce MM bone disease in SCID--rab mice. Mice treated with AS-ARH cells were preserved, exhibited no radiologically identifiable lytic lesions and, unlike the controls treated with EV-ARH cells, lived longer and showed reduced tumor burden. Consistently, bones harboring AS-ARH cells showed marked reductions of RANKL expression and osteoclast density compared to the controls harboring EV-ARH cells. These results provide further support for the potential osteoclastogenic effects of BDNF, which may mediate stromal--MM cell interactions to upregulate RANKL secretion, in myeloma bone diseases. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is a novel gasotransmitter that inhibits L-type calcium currents (I Ca, L). However, the underlying molecular mechanisms are unclear. In particular, the targeting site in the L-type calcium channel where H2S functions remains unknown. The study was designed to investigate if the sulfhydryl group could be the possible targeting site in the L-type calcium channel in rat cardiomyocytes. Cardiac function was measured in isolated perfused rat hearts. The L-type calcium currents were recorded by using a whole cell voltage clamp technique on the isolated cardiomyocytes. The L-type calcium channel containing free sulfhydryl groups in H9C2 cells were measured by using Western blot. The results showed that sodium hydrosulfide (NaHS, an H2S donor) produced a negative inotropic effect on cardiac function, which could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM). H2S donor inhibited the peak amplitude of I Ca, L in a concentration-dependent manner. However, dithiothreitol (DTT), a reducing sulfhydryl modifier markedly reversed the H2S donor-induced inhibition of I Ca, L in cardiomyocytes. In contrast, in the presence of DM, H2S donor could not alter cardiac function and L type calcium currents. After the isolated rat heart or the cardiomyocytes were treated with DTT, NaHS could markedly alter cardiac function and L-type calcium currents in cardiomyocytes. Furthermore, NaHS could decrease the functional free sulfhydryl group in the L-type Ca2+ channel, which could be reversed by thiol reductant, either DTT or reduced glutathione. Therefore, our results suggest that H2S might inhibit L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes. [ABSTRACT FROM AUTHOR]

Background: Small sample sizes used in previous studies result in a lack of overlap between the reported gene signatures for prediction of chemotherapy response. Although morphologic features, especially tumor nuclear morphology, are important for cancer grading, little research has been reported on quantitatively correlating cellular morphology with chemotherapy response, especially in a large data set. In this study, we have used a large population of patients to identify molecular and morphologic signatures associated with chemotherapy response in serous ovarian carcinoma. Methodology/Principal Findings: A gene expression model that predicts response to chemotherapy is developed and validated using a large-scale data set consisting of 493 samples from The Cancer Genome Atlas (TCGA) and 244 samples from an Australian report. An identified 227-gene signature achieves an overall predictive accuracy of greater than 85% with a sensitivity of approximately 95% and specificity of approximately 70%. The gene signature significantly distinguishes between patients with unfavorable versus favorable prognosis, when applied to either an independent data set (P = 0.04) or an external validation set (P,0.0001). In parallel, we present the production of a tumor nuclear image profile generated from 253 sample slides by characterizing patients with nuclear features (such as size, elongation, and roundness) in incremental bins, and we identify a morphologic signature that demonstrates a strong association with chemotherapy response in serous ovarian carcinoma. Conclusions: A gene signature discovered on a large data set provides robustness in accurately predicting chemotherapy response in serous ovarian carcinoma. The combination of the molecular and morphologic signatures yields a new understanding of potential mechanisms involved in drug resistance. [ABSTRACT FROM AUTHOR]

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS. [ABSTRACT FROM AUTHOR]