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Expression of FosB gene in striatum is essential in addiction establishment. Activated glucocorticoid receptors (GRs) induce FosB gene expression in response to stressor. Therefore, elevation of FosB expression in striatum serves as one mechanism by which stress increases risk for addiction. In this study, adult male Sprague-Dawley rats were used to investigate whether chronic stress result in histone modifications at FosB gene promoter in striatum and how these histone modifications affect FosB expression and the establishment of addiction behavior after administration of drugs of abuse. Animals were randomly assigned to three groups: Electric foot shock (EFS) group received 7-day EFS to induce chronic stress; electric foot shock plus mifepristone (EFS + Mif) group were injected with mifepristone, a nonspecific GRs antagonist, before EFS; control group did not receive any EFS. All groups then received 2-day conditioned place preference (CPP) training with morphine (5 mg/kg body weight) to test vulnerability to drug addiction. Before and after morphine administration, FosB mRNA in striatum was quantified by real-time RT-PCR. Levels of histone H3/H4 acetylation and histone H3K4 dimethylation at FosB promoter in striatum after morphine administration were measured by using chromatin immunoprecipitation (ChIP) plus real-time PCR. EFS group had stronger place preference to morphine and had significantly higher level of FosB mRNA in striatum than the other two groups. H3K4 dimethylation was 2.6-fold higher in EFS group than control group, while no statistical difference in H3/H4 acetylation. Mifepristone administration before EFS decreased histone H3K4 dimethylation and FosB mRNA in striatum, and also diminished morphine-induced conditioned place preference. Altogether, increased level of H3K4 dimethylation at FosB promoter in striatum is partially dependent on the activation of GR and responsible for the elevated level of morphine-induced FosB mRNA in chronic stressed animals. [ABSTRACT FROM AUTHOR]

Background: Vitamin D may play a role in skeletal muscle because of the discovery of VDR in skeletal muscle. However, vitamin D deficiency is a global problem, including athletes. Studies examining the effect of vitamin D supplementation on muscle function in athletes have inconsistent results. Therefore, we aimed to quantitatively summarize the evidence for the effect of vitamin D supplementation on skeletal muscle strength and explosive power of athletes using a meta-analysis. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for studies to identify randomized controlled trials or controlled trials meeting the inclusion criteria. By a meta-analysis, effect sizes (standardized mean differences, SMD) with 95% confidence intervals (CI) was calculated to compare reported outcomes across studies, I2 index was used to assessing heterogeneity, and heterogeneity factors were identified by regression analysis. The potential publication and sensitivity analyses were also assessed. Results: Eight RCTs involving 284 athletes were included. The protocols used to evaluate the muscle strength of athletes were inconsistent across the included studies, and muscle explosive power was assessed via vertical jump tests. The results indicated that vitamin D supplementation had no impact on overall muscle strength outcomes (SMD 0.05, 95% CI: -0.39 to 0.48, p = 0.84). In subgroup analysis, vitamin D supplementation had an effect on lower-limb muscle strength (SMD 0.55, 95% CI:0.12 to 0.98, p = 0.01) but not upper-limb muscle strength (SMD -0.19, 95% CI:-0.73 to 0.36, p = 0.50) or muscle explosive power (SMD 0.05, 95% CI:-0.24 to 0.34, p = 0.73). Vitamin D supplementation was more effective for athletes trained indoors (SMD 0.48, 95% CI:0.06 to 0.90, p = 0.02). Conclusions: Vitamin D supplementation positively affected lower limb muscle strength in athletes, but not upper limb muscle strength or muscle power. Different muscle groups and functions may respond differently to vitamin D supplementation. Additional studies should focus on determining the appropriate vitamin D supplementation methods and optimal serum 25(OH)D levels for athletes. Registration: The protocol for our study is registered in the international prospective register of systematic reviews (PROSPERO registration number ). [ABSTRACT FROM AUTHOR]

The DEP1 (dense and erect panicle 1) gene, which corresponds to the erect panicle architecture, shows a pleiotropic effect in increasing grain yield and nitrogen use efficiency (NUE) in rice. Nevertheless, it remains unclear whether the carbon−nitrogen metabolic balance changes as the dep1 allele enhances nitrogen uptake and assimilation. In this study, we generated transgenic Akitakomati plants by overexpressing dep1 and analyzed the carbon−nitrogen metabolic status, gene expression profiles, and grain yield and quality. Under either low or high nitrogen growth conditions, the carbon−nitrogen metabolic balance of dep1-overexpressed lines was broken in stem sheaths and leaves but not in grains; the dep1-overexpressed plants showed higher expressions of glutamine synthetase (GS) and glutamate synthase (GOGAT) genes than the wildtype, along with increased total nitrogen and soluble protein content in the straw at maturity. However, the ribulose-1,5-bisphosphate carboxylase/oxygenase (RUBISCO) and phosphoenolpyruvate carboxylase (PEPC) genes were downregulated in dep1-overexpressed plants, leading to a decreased carbohydrate content and carbon/nitrogen ratio. Although the unbalanced carbon−nitrogen metabolism decreased the grain-filling rate, grain setting percentage, 1000 grain weight, and grain quality in dep1-overexpressed lines, it led to increased grain numbers per panicle and consequently increased grain yield. Our results suggest that an unbalanced carbon−nitrogen metabolic status is a major limiting factor for further improving grain yield and quality in erect panicle varieties. [ABSTRACT FROM AUTHOR]

Traffic congestion in freeway network is a prevalent transportation problem and leads to a strong degradation of freeway network facilities. This paper proposes a new coordinated optimization approach for freeway network, aiming to relieve the traffic congestion in freeway network equipped with the coordinated traffic controllers. The challenge is how to solve the problem between the traffic control goals of each path and those of the network. In this paper, the bi-level programming theory is used to address this problem. More exactly, in the path level, the optimal control model is designed to relieve congestion in each path of the test network. Furthermore, in the network level, the optimal model considers the traffic equilibrium and cost optimization. The efficiency of the proposed approach is tested on a well-known traffic network calibrated by the field test data of freeway network. The results show that the proposed approach has positive effects in balancing traffic load and improving the service level of freeway networks. [ABSTRACT FROM AUTHOR]

During the neonatal period, the ability to generate immune effector and memory responses to vaccines or pathogens is often questioned. This study was undertaken to obtain a global view of the natural differences in the expression of immune genes early in life. Our hypothesis was that transcriptome analyses of peripheral blood mononuclear cells (PBMCs) of foals (on day 1 and day 42 after birth) and adult horses would show differential gene expression profiles that characterize natural immune processes. Gene ontology enrichment analysis provided assessment of biological processes affected by age, and a list of 897 genes with ≥2 fold higher (p<0.01) expression in day 42 when compared to day 1 foal samples. Up-regulated genes included B cell and T cell receptor diversity genes; DNA replication enzymes; natural killer cell receptors; granzyme B and perforin; complement receptors; immunomodulatory receptors; cell adhesion molecules; and cytokines/chemokines and their receptors. The list of 1,383 genes that had higher (p<0.01) expression on day 1 when compared to day 42 foal samples was populated by genes with roles in innate immunity such as antimicrobial proteins; pathogen recognition receptors; cytokines/chemokines and their receptors; cell adhesion molecules; co-stimulatory molecules; and T cell receptor delta chain. Within the 742 genes with increased expression between day 42 foal and adult samples, B cell immunity was the main biological process (p = 2.4E-04). Novel data on markedly low (p<0.0001) TLR3 gene expression, and high (p≤0.01) expression of IL27, IL13RA1, IREM-1, SIRL-1, and SIRPα on day 1 compared to day 42 foal samples point out potential mechanisms of increased susceptibility to pathogens in early life. The results portray a progression from innate immune gene expression predominance early in life to adaptive immune gene expression increasing with age with a putative overlay of immune suppressing genes in the neonatal phase. These results provide insight to the unique attributes of the equine neonatal and young immune system, and offer many avenues of future investigation. [ABSTRACT FROM AUTHOR]

Background and Objective: Genetic factors including TNF-β have been considered as important components in the aetiology of migraine. Many studies have investigated the association between TNF-β 252A>G polymorphism and migraine risk, with debatable results. This study was designed to examine whether the TNF-β 252A>G polymorphism confers genetic susceptibility to migraine in diverse populations. Method: Studies eligible for this meta-analysis were searched in the PubMed, Embase, and CNKI by using the keywords “tumor necrosis factor”, “TNF”, “252A>G”, “rs909253”, “polymorphism”, “polymorphisms”, “variant”, “SNP”, combined with “migraine” or “migraine with aura (MA)” or “migraine without aura (MO)”. Pooled ORs and 95% CI were appropriately calculated using the fixed-effect model. Results: We finally included a total of seven studies, providing 5 557 migraineurs and 20 543 unrelated healthy controls. Meta-analysis results showed no statistical evidence of a significant association between TNF-β 252A>G polymorphism and overall migraine risk. Stratified analyses by type of migraine and gender revealed similar results. Interestingly, an OR with 95% CI representing an increased migraine risk was indicated in Asians under the recessive model (GG vs. AG + AA: OR, 1.38; 95%CI, 1.04–1.84; P for heterogeneity, 0.665). Conclusions: Our findings appear to support the hypothesis that genetic variability of 252A>G polymorphism in TNF region may modulate risk of migraine in the population of Asian ancestry. [ABSTRACT FROM AUTHOR]

Radioactive immunoassay (RIA) is a traditional serum hormone assay method, but the application of the method in reproductive studies is limited by the associated radioactivity. The aim of present study was to evaluate the reliability of RIA and to compare its canine serum progesterone concentration determination accuracy to that of the electric chemiluminescence immunoassay (ECLI). In vivo matured oocytes were utilized for canine somatic cell nuclear transfer (SCNT), and serum progesterone levels were assessed to accurately determine ovulation and oocyte maturation. Canine serum progesterone concentrations during both proestrus and estrus were analyzed by RIA and ECLI to determine the ovulation day. Although both methods detected similar progesterone levels before ovulation, the mean progesterone concentration determined using ECLI was significantly higher than of RIA three days before ovulation. Following ovulation, oocytes were collected by surgery, and a lower percentage of mature oocytes were observed using ECLI (39%) as compared to RIA (67%) if 4-8ng/ml of progesterone were used for determination of ovulation. A high percentage of mature oocytes was observed using ECLI when 6–15 ng/mL of progesterone was used for ovulation determination. To determine whether ECLI could be used for canine cloning, six canines were selected as oocyte donors, and two puppies were obtained after SCNT and embryo transfer. In conclusion, compared to the traditional RIA method, the ECLI method is a safe and reliable method for canine cloning. [ABSTRACT FROM AUTHOR]

The aims of this study are to identify the most important predictors of total diagnosed and undiagnosed diabetes and estimate the mean change in the predicted probability among aged 45+ adults in China. We used baseline data collected from 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) (n = 9,513). First, we estimated the prevalence of diagnosed, measured, total diagnosed, and undiagnosed diabetes. Second, we used probit models to determine whether individual attributes, socioeconomic characteristics and behavioral health factors, including smoking, alcohol consumption, obesity, central obesity, are associated with total diagnosed and undiagnosed diabetes. We also consider other factors, including contact with medical system, hypertension and urban/rural settings. Third, we estimated average marginal effects of variables in probit models. Among Chinese people aged 45+, the prevalence of diagnosed, measured, total diagnosed and undiagnosed diabetes were 5.8% (95%CI, 5.3%-6.3%), 14.7% (95%CI, 14.0%-15.4%), 17.0% (95%CI, 16.3%-17.7%), 11.3% (95%CI, 10.6%-12.0%), respectively. The probability of total diagnosed diabetes is 3.3% (95% CI, 1.2%-5.3%) and 10.2% (95% CI, 7.0%-13.5%) higher for overweight and obesity than normal BMI, 5.0% (95% CI, 3.0%-7.1%) higher for central obesity than normal waist circumference, 5.4% (95% CI, 3.7%-7.0%) higher for hypertensive than normotensive and 1.8% (95% CI, 0.8%- 2.7%) higher in urban areas than in rural areas, respectively. The probability of undiagnosed diabetes is 2.7% (95% CI, 1.2%-4.2%) and 7.2% (95% CI, 4.7%-9.6%) higher for overweight and obesity than normal BMI, 2.6% (95% CI, 0.9%-4.4%) higher for central obesity than normal waist circumference and 2.6% (95% CI, 1.2%-4.0%) higher for hypertensive than normotensive, respectively, and -1.5% (95% CI, -2.5% to -0.5%) lower for individuals who were in contact with the medical system. Greater focus on prevention of diabetes is necessary for obesity, central obesity, hypertensive and in urban areas for middle-aged and older in China. [ABSTRACT FROM AUTHOR]

The study objective was to retrospectively analyze the metabolic variables derived from 18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as predictors of progression-free survival (PFS) and overall survival (OS) in advanced lung adenocarcinoma stratified by epidermal growth factor receptor (EGFR) mutation status. A total of 176 patients (91, EGFR mutation; 85, wild-type EGFR) who underwent 18F-FDG PET/CT before treatment were enrolled. The main 18F-FDG PET/CT-derived variables: primary tumor maximum standardized uptake value (SUVmaxT), primary tumor total lesion glycolysis (TLGT), the maximum SUVmax of all selected lesions in whole body determined using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (SUVmaxWBR), and whole-body total TLG determined using the RECIST 1.1 criteria (TLGWBR) were measured. Survival analysis regarding TLGWBR, and other factors in advanced lung adenocarcinoma patients stratified using EGFR mutation status, were evaluated. The results indicated that high TLGWBR (≥259.85), EGFR wild-type, and high serum LDH were independent predictors of worse PFS and OS in all patients with advanced lung adenocarcinoma. Among patients with wild-type EGFR, only TLGWBR retained significance as an independent predictor of both PFS and OS. Among patients with the EGFR mutation, high serum LDH level was an independent predictor of worse PFS and OS, and high TLGWBR (≥259.85) was an independent predictor of worse PFS but not worse OS. In conclusion, TLGWBR is a promising parameter for prognostic stratification of patients with advanced lung adenocarcinoma and EGFR status; however, it cannot be used to further stratify the risk of worse OS for patients with the EGFR mutation. Further prospective studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Water undergoes structural change as it interfaces with hydrophilic surfaces, including the many hydrophilic surfaces within the cell. This interfacial water has become known as “Exclusion Zone (EZ) water” or “fourth-phase water” []. Methods: We tested the hypothesis that anesthetics diminish the amount of EZ water, and that this change may correlate with functional changes in anesthesia. By using the local anesthetics Lidocaine and Bupivacaine as well as a general inhalational anesthetic, Isoflurane, we tracked the EZ size as these anesthetics were introduced. Results: All three anesthetics diminished EZ size in a concentration-dependent manner at concentrations of 0.18 mM and greater for Bupivacaine, 0.85 mM and greater for Lidocaine, and 0.2% for Isoflurane. At extremely low (micromolar) concentrations, however, all three anesthetics increased EZ size. Conclusions: The sharp increase of EZ size associated with micromolar anesthetic concentrations follows a similar pattern to induction of general anesthesia, from the excitation stage (Stage II) to the depression and overdose stages of surgical anesthesia (Stages III and IV). The results are consistent with the hypothesis that anesthetics may act on water, a fundamental organizational component common to all cells. [ABSTRACT FROM AUTHOR]

Virtually all studies of plant-herbivore-natural enemy interactions focus on plant quality as the major constraint on development and survival. However, for many gregarious feeding insect herbivores that feed on small or ephemeral plants, the quantity of resources is much more limiting, yet this area has received virtually no attention. Here, in both lab and semi-field experiments using tents containing variably sized clusters of food plants, we studied the effects of periodic food deprivation in a tri-trophic system where quantitative constraints are profoundly important on insect performance. The large cabbage white Pieris brassicae, is a specialist herbivore of relatively small wild brassicaceous plants that grow in variable densities, with black mustard (Brassica nigra) being one of the most important. Larvae of P. brassicae are in turn attacked by a specialist endoparasitoid wasp, Cotesia glomerata. Increasing the length of food deprivation of newly molted final instar caterpillars significantly decreased herbivore and parasitoid survival and biomass, but shortened their development time. Moreover, the ability of caterpillars to recover when provided with food again was correlated with the length of the food deprivation period. In outdoor tents with natural vegetation, we created conditions similar to those faced by P. brassicae in nature by manipulating plant density. Low densities of B. nigra lead to potential starvation of P. brassicae broods and their parasitoids, replicating nutritional conditions of the lab experiments. The ability of both unparasitized and parasitized caterpillars to find corner plants was similar but decreased with central plant density. Survival of both the herbivore and parasitoid increased with plant density and was higher for unparasitized than for parasitized caterpillars. Our results, in comparison with previous studies, reveal that quantitative constraints are far more important that qualitative constraints on the performance of gregarious insect herbivores and their gregarious parasitoids in nature. [ABSTRACT FROM AUTHOR]

One of the reasons for the progressive yield decline observed in cereals production is the rapid build-up of populations of the cereal cyst nematode (CCN, Heterodera avenae). These nematodes secrete so-call effectors into their host plant to suppress the plant defense responses, alter plant signaling pathways and then induce the formation of syncytium after infection. However, little is known about its molecular mechanism and parasitism during incompatible infection. To gain insight into its repertoire of parasitism genes, we investigated the transcriptome of the early parasitic second-stage (30 hours, 3 days and 9 days post infection) juveniles of the CCN as well as the CCN infected tissue of the host Aegilops variabilis by Illumina sequencing. Among all assembled unigenes, 681 putative genes of parasitic nematode were found, in which 56 putative effectors were identified, including novel pioneer genes and genes corresponding to previously reported effectors. All the 681 CCN unigenes were mapped to 229 GO terms and 200 KEGG pathways, including growth, development and several stimulus-related signaling pathways. Sixteen clusters were involved in the CCN unigene expression atlas at the early stages during infection process, and three of which were significantly gene-enriched. Besides, the protein-protein interaction network analysis revealed 35 node unigenes which may play an important role in the plant-CCN interaction. Moreover, in a comparison of differentially expressed genes between the pre-parasitic juveniles and the early parasitic juveniles, we found that hydrolase activity was up-regulated in pre J2s whereas binding activity was upregulated in infective J2s. RT-qPCR analysis on some selected genes showed detectable expression, indicating possible secretion of the proteins and putative role in infection. This study provided better insights into the incompatible interaction between H. avenae and the host plant Ae. varabilis. Moreover, RNAi targets with potential lethality were screened out and primarily validated, which provide candidates for engineering-based control of cereal cyst nematode in crops breeding. [ABSTRACT FROM AUTHOR]

The objective of this paper is to extract concave and convex feature regions via segmenting surface mesh of a mechanical part whose surface geometry exhibits drastic variations and concave-convex features are equally important when modeling. Referring to the original approach based on the minima rule (MR) in cognitive science, we have created a revised minima rule (RMR) and presented an improved approach based on RMR in the paper. Using the logarithmic function in terms of the minimum curvatures that are normalized by the expectation and the standard deviation on the vertices of the mesh, we determined the solution formulas for the feature vertices according to RMR. Because only a small range of the threshold parameters was selected from in the determined formulas, an iterative process was implemented to realize the automatic selection of thresholds. Finally according to the obtained feature vertices, the feature edges and facets were obtained by growing neighbors. The improved approach overcomes the inherent inadequacies of the original approach for our objective in the paper, realizes full automation without setting parameters, and obtains better results compared with the latest conventional approaches. We demonstrated the feasibility and superiority of our approach by performing certain experimental comparisons. [ABSTRACT FROM AUTHOR]

The present study was mainly conducted to determine whether dietary leucine supplementation could attenuate the decrease of the mucin production in the jejunal mucosa of weaned pigs infected by porcine rotavirus (PRV). A total of 24 crossbred barrows weaned at 21 d of age were assigned randomly to 1 of 2 diets supplemented with 1.00% L-leucine or 0.68% L-alanine (isonitrogenous control) for 17 d. On day 11, all pigs were orally infused PRV or the sterile essential medium. During the first 10 d of trial, dietary leucine supplementation could improve the feed efficiency (P = 0.09). The ADG and feed efficiency were impaired by PRV infusion (P<0.05). PRV infusion also increased mean cumulative score of diarrhea, serum rotavirus antibody concentration and crypt depth of the jejunal mucosa (P<0.05), and decreased villus height: crypt depth (P = 0.07), goblet cell numbers (P<0.05), mucin 1 and 2 concentrations (P<0.05) and phosphorylated mTOR level (P<0.05) of the jejunal mucosa in weaned pigs. Dietary leucine supplementation could attenuate the effects of PRV infusion on feed efficiency (P = 0.09) and mean cumulative score of diarrhea (P = 0.09), and improve the effects of PRV infusion on villus height: crypt depth (P = 0.06), goblet cell numbers (P<0.05), mucin 1 (P = 0.08) and 2 (P = 0.07) concentrations and phosphorylated mTOR level (P = 0.08) of the jejunal mucosa in weaned pigs. These results suggest that dietary 1% leucine supplementation alleviated the decrease of mucin production and goblet cell numbers in the jejunal mucosa of weaned pigs challenged by PRV possibly via activation of the mTOR signaling. [ABSTRACT FROM AUTHOR]

In 2010 the American Heart Association proposed a definition of ideal health behaviors and health factors to measure cardiovascular health, from which Huffman et al. created the Cardiovascular Health Score (CVH score) to estimate these metrics on an individual level. We performed a prospective cohort study among employees of the Kailuan Group Corporation, who underwent a physical examination in 2006–2007 to investigate the relationship between the CVH score and the risk of cardiovascular disease (CVD). A total of 91,598 individuals free of stroke and myocardial infarction at baseline were included in the final analysis. We calculated baseline CVH score for each metric (poor=0, intermediate=1, ideal=2 points; range=0–14 points for all seven metrics) and categorized them into three groups: inadequate (0–4 points), average (5–9 points), and optimum (10–14 points). Incidence of total number of CVD events, myocardial infarction, and stroke was analyzed among these three groups and each incremental point on the CVH score. During an average 6.81 years of follow-up, there were 3276 CVD events, 2579 strokes and 747 myocardial infarction occurred. After adjusting for several confounding factors, each better health category of the CVH score was associated with reduced odds of 47% for all CVD events, and each point higher on the CVH score was associated with reduced odds of 18%. Similar trends were detected in the risks for myocardial infarction and stroke. A higher CVH score is therefore a protective factor for CVD, myocardial infarction, and stroke. [ABSTRACT FROM AUTHOR]

Nanoimprinting lithography (NIL) is a manufacturing process that can produce macroscale surface areas with nanoscale features. In this paper, this technique is used to solve three fundamental issues for the application of localized surface plasmonic resonance (LSPR) in practical clinical measurements: assay sensitivity, chip-to-chip variance, and the ability to perform assays in human serum. Using NIL, arrays of 140 nm square features were fabricated on a sensing area of 1.5 mm x 1.5 mm with low cost. The high reproducibility of NIL allowed for the use of a one-chip, one-measurement approach with 12 individually manufactured surfaces with minimal chip-to-chip variations. To better approximate a real world setting, all chips were modified with a biocompatible, multi-component monolayer and inter-chip variability was assessed by measuring a bioanalyte standard (2.5−75 ng/ml) in the presence of a complex biofluid, human serum. In this setting, nanoimprinted LSPR chips were able to provide sufficient characteristics for a ‘low-tech’ approach to laboratory-based bioanalyte measurement, including: 1) sufficient size to interface with a common laboratory light source and detector without the need for a microscope, 2) high sensitivity in serum with a cardiac troponin limit of detection of 0.55 ng/ml, and 3) very low variability in chip manufacturing to produce a figure of merit (FOM) of 10.5. These findings drive LSPR closer to technical comparability with ELISA-based assays while preserving the unique particularities of a LSPR based sensor, suitability for multiplexing and miniaturization, and point-of-care detections. [ABSTRACT FROM AUTHOR]

LIN28B is involved in “stemness” and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

Background: Angiotensin II (AngII) participates in endothelial damage and inflammation, and accelerates atherosclerosis. Endothelial lipase (EL) is involved in the metabolism and clearance of high density lipoproteins (HDL), the serum levels of which correlate negatively with the onset of cardiovascular diseases including atherosclerosis. However, the relationship between AngII and EL is not yet fully understood. In this study, we investigated the effects of AngII on the expression of EL and the signaling pathways that mediate its effects in human umbilical vein endothelial cells (HUVECs). Methods and Findings: HUVECs were cultured in vitro with different treatments as follows: 1) The control group without any treatment; 2) AngII treatment for 0 h, 4 h, 8 h, 12 h and 24 h; 3) NF-κB activation inhibitor pyrrolidine dithiocarbamate (PDTC) pretreatment for 1 h before AngII treatment; and 4) mitogen-activated protein kinase (MAPK) p38 inhibitor (SB203580) pretreatment for 1 h before AngII treatment. EL levels in each group were detected by immunocytochemical staining and western blotting. HUVECs proliferation was detected by MTT and proliferating cell nuclear antigen (PCNA) immunofluorescence staining. NF-kappa B (NF-κB) p65, MAPK p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) expression levels were assayed by western blotting. The results showed that the protein levels of EL, NF-κB p65, MAPK p38, JNK, and p-ERK protein levels, in addition to the proliferation of HUVECs, were increased by AngII. Both the NF-kB inhibitor (PDTC) and the MAPK p38 inhibitor (SB203580) partially inhibited the effects of AngII on EL expression. Conclusion: AngII may upregulate EL protein expression via the NF-κB and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase resistance has been well documented in many insects, including several mosquito species. We tested the resistance of five wild, Chinese strains of the mosquito Culex pipiens quinquefasciatus to two kinds of pesticides, dichlorvos and propoxur. An acetylcholinesterase gene (ace1) was cloned and sequenced from a pooled sample of mosquitoes from these five strains and the amino acids of five positions were found to vary (V185M, G247S, A328S, A391T, and T682A). Analysis of the correlation between mutation frequencies and resistance levels (LC50) suggests that two point mutations, G247S (r2 = 0.732, P = 0.065) and A328S (r2 = 0.891, P = 0.016), are associated with resistance to propoxur but not to dichlorvos. Although the V185M mutation was not associated with either dichlorvos or propoxur resistance, its RS genotype frequency was correlated with propoxur resistance (r2 = 0.815, P = 0.036). And the HWE test showed the A328S mutation is linked with V185M, also with G247S mutation. This suggested that these three mutations may contribute synergistically to propoxur resistance. The T682A mutation was negatively correlated with propoxur (r2 = 0.788, P = 0.045) resistance. Knowledge of these mutations may help design strategies for managing pesticide resistance in wild mosquito populations. [ABSTRACT FROM AUTHOR]

Background: As one of the most common types of co-regulatory motifs, feed-forward loops (FFLs) control many cell functions and play an important role in human cancers. Therefore, it is crucial to reconstruct and analyze cancer-related FFLs that are controlled by transcription factor (TF) and microRNA (miRNA) simultaneously, in order to find out how miRNAs and TFs cooperate with each other in cancer cells and how they contribute to carcinogenesis. Current FFL studies rely on predicted regulation information and therefore suffer the false positive issue in prediction results. More critically, FFLs generated by existing approaches cannot represent the dynamic and conditional regulation relationship under different experimental conditions. Methodology/Principal Findings: In this study, we proposed a novel filter-wrapper feature selection method to accurately identify co-regulatory mechanism by incorporating prior information from predicted regulatory interactions with parallel miRNA/mRNA expression datasets. By applying this method, we reconstructed 208 and 110 TF-miRNA co-regulatory FFLs from human pan-cancer and prostate datasets, respectively. Further analysis of these cancer-related FFLs showed that the top-ranking TF STAT3 and miRNA hsa-let-7e are key regulators implicated in human cancers, which have regulated targets significantly enriched in cellular process regulations and signaling pathways that are involved in carcinogenesis. Conclusions/Significance: In this study, we introduced an efficient computational approach to reconstruct co-regulatory FFLs by accurately identifying gene co-regulatory interactions. The strength of the proposed feature selection method lies in the fact it can precisely filter out false positives in predicted regulatory interactions by quantitatively modeling the complex co-regulation of target genes mediated by TFs and miRNAs simultaneously. Moreover, the proposed feature selection method can be generally applied to other gene regulation studies using parallel expression data with respect to different biological contexts. [ABSTRACT FROM AUTHOR]

The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21WAF/Cip1 (P<0.01), cleaved caspase 3, and the caspase-cleaved product of cytokeratin 18. Decreased levels of VEGF (P<0.01) and reduced vessel size (P<0.05) were also observed, the latter only in the ZM198,615-pretreatment group. Furthermore, we performed a series of in vitro studies using the colon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells. [ABSTRACT FROM AUTHOR]

Th17 cells have been implicated in the pathogenesis of myocarditis. Interleukin (IL)-17A produced by Th17 cells is dispensable for viral myocarditis but essential for the progression to dilated cardiomyopathy (DCM). This study investigated whether the adenoviral transfer of the IL-17 receptor A reduces myocardial remodeling and dysfunction in viral myocarditis leading to DCM. In a mouse model of Coxsackievirus B3 (CVB3)-induced chronic myocarditis, the delivery of the adenovirus-containing IL-17 receptor A (Ad-IL17RA:Fc) reduced IL-17A production and decreased the number of Th17 cells in the spleen and heart, leading to the down-regulation of systemic TNF-α and IL-6 production. Cardiac function improved significantly in the Ad-IL17R:Fc- compared with the Ad-null-treated mice 3 months after the first CVB3 infection. Ad-IL17R:Fc reduced the left ventricle dilation and decreased the mortality in viral myocarditis, leading to DCM (56% in the Ad-IL17R:Fc versus 76% in the Ad-null group). The protective effects of Ad-IL17R-Fc on remodeling correlated with the attenuation of myocardial collagen deposition and the reduction of fibroblasts in CVB3-infected hearts, which was accompanied by the down-regulation of A distintegrin and metalloprotease with thrombospondin type 1 motifs (ADAMTS-1), Matrix metalloproteinase-2(MMP-2), and collagen subtypes I and III in the heart. Moreover, in cultured cardiac fibroblasts, IL-17A induced the expression of ADAMTS-1, MMP-2, and collagen subtypes I and III and increased the proliferation of fibroblasts. We determined that the delivery of IL-17-RA:Fc reduces cardiac remodeling, improves function, and decreases mortality in viral myocarditis leading to DCM, possibly by suppressing fibrosis. Therefore, the adenoviral transfer of the IL-17 receptor A may represent an alternative therapy for chronic viral myocarditis and its progression to DCM. [ABSTRACT FROM AUTHOR]

Objective: To examine the distribution of HIV-1 genotypes among injecting drug users (IDUs) from Dehong, Yunnan province. Materials and Methods: Blood samples from a total of 95 HIV-positive IDUs were retrospectively analyzed. Samples were collected between 2005 and 2009 from four cities in Dehong prefecture, western Yunnan province, the geographical origin of the HIV epidemic in China. HIV-1 gag, partial pol, vpr-env fragment, half-genome, or near-full-length sequences were analyzed to determine the HIV-1 genotypes of each subject. Results were compared with findings from past studies of IDUs in Dehong and in neighboring Myanmar. Results: We observed a high prevalence of B′/C recombinants (82.4%) among IDUs in Dehong, the structural profiles of which do not match those previously reported in Dehong or in Myanmar. Furthermore, statistically significant differences in geographical and temporal distributions of HIV-1 genotypes were characterized by a predominance of HIV-1 B′/C recombinant forms among older subjects(p = 0.034), subjects from Longchuan district (p = 0.022), and subjects diagnosed between 2000 and 2004 (p = 0.004). Conclusions: The increasing prevalence of multiple, new B′/C recombinant forms suggest that HIV-1 intersubtype recombination is substantial and ongoing in western Yunnan. This reflects the high-risk behavior of IDUs in this region and argues the need for stronger monitoring and prevention measures in Dehong and other high-prevalence areas around China. [ABSTRACT FROM AUTHOR]

The shoot apical meristem (SAM) is the source of all of the above-ground tissues and organs in post-embryonic development in higher plants. Studies have proven that the expression of genes constituting the WUSCHEL (WUS)-CLAVATA (CLV) feedback loop is critical for the SAM maintenance. Several histone lysine acetylation and methylation markers have been proven to regulate the transcription level of WUS. However, little is known about how histone arginine methylation regulates the expression of WUS and other genes. Here, we report that H4R3 symmetric dimethylation (H4R3sme2) mediated by SKB1/PRMT5 represses the expression of CORYNE (CRN) to maintain normal SAM geometrics. SKB1 lesion results in small SAM size in Arabidopsis, as well as down-regulated expression of WUS and CLV3. Up-regulation of WUS expression enlarges SAM size in skb1 mutant plants. We find that SKB1 and H4R3sme2 associate with the chromatin of the CRN locus to down-regulate its transcription. Mutation of CRN rescues the expression of WUS and the small SAM size of skb1. Thus, SKB1 and SKB1-mediated H4R3sme2 are required for the maintenance of SAM in Arabidopsis seedlings. [ABSTRACT FROM AUTHOR]

Background: Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear. Methods: Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery. These specimens were divided into three groups based on age: group A (age 0–6 months), group B (age, 7–12 months), and group C (>12 months). Each tissue specimen was subjected to DNA extraction, RNA extraction, and immunofluorescence. Results: Immunofluorescence and qRT-PCR analysis revealed that DNA damage markers—mitochondrial DNA copy number, oxoguanine 8, and phosphorylated ataxia telangiectasia mutated—were highest in Group B. However immunofluorescence and qRT-PCR demonstrated that two cell proliferation markers, Ki67 and cyclin D2, were decreased with age. In addition, wheat germ agglutinin-staining indicated that the average size of cardiomyocytes increased with age. Conclusions: Oxidative DNA damage of cardiomyocytes was not correlated positively with age in human beings. Oxidative DNA damage is unable to fully explain the reduced proliferation of human cardiomyocytes. [ABSTRACT FROM AUTHOR]

Leaves of C4 crops usually have higher radiation, water and nitrogen use efficiencies compared to the C3 species. Engineering C4 traits into C3 crops has been proposed as one of the most promising ways to repeal the biomass yield ceiling. To better understand the function of C4 photosynthesis, and to identify candidate genes that are associated with the C4 pathways, a comparative transcription network analysis was conducted on leaf developmental gradients of three C4 species including maize, green foxtail and sorghum and one C3 species, rice. By combining the methods of gene co-expression and differentially co-expression networks, we identified a total of 128 C4 specific genes. Besides the classic C4 shuttle genes, a new set of genes associated with light reaction, starch and sucrose metabolism, metabolites transportation, as well as transcription regulation, were identified as involved in C4 photosynthesis. These findings will provide important insights into the differential gene regulation between C3 and C4 species, and a good genetic resource for establishing C4 pathways in C3 crops. [ABSTRACT FROM AUTHOR]

Genotyping by sequencing (GBS) provides opportunities to generate high-resolution genetic maps at a low genotyping cost, but for highly heterozygous species, missing data and heterozygote undercalling complicate the creation of GBS genetic maps. To overcome these issues, we developed a publicly available, modular approach called HetMappS, which functions independently of parental genotypes and corrects for genotyping errors associated with heterozygosity. For linkage group formation, HetMappS includes both a reference-guided synteny pipeline and a reference-independent de novo pipeline. The de novo pipeline can be utilized for under-characterized or high diversity families that lack an appropriate reference. We applied both HetMappS pipelines in five half-sib F1 families involving genetically diverse Vitis spp. Starting with at least 116,466 putative SNPs per family, the HetMappS pipelines identified 10,440 to 17,267 phased pseudo-testcross (Pt) markers and generated high-confidence maps. Pt marker density exceeded crossover resolution in all cases; up to 5,560 non-redundant markers were used to generate parental maps ranging from 1,047 cM to 1,696 cM. The number of markers used was strongly correlated with family size in both de novo and synteny maps (r = 0.92 and 0.91, respectively). Comparisons between allele and tag frequencies suggested that many markers were in tandem repeats and mapped as single loci, while markers in regions of more than two repeats were removed during map curation. Both pipelines generated similar genetic maps, and genetic order was strongly correlated with the reference genome physical order in all cases. Independently created genetic maps from shared parents exhibited nearly identical results. Flower sex was mapped in three families and correctly localized to the known sex locus in all cases. The HetMappS pipeline could have wide application for genetic mapping in highly heterozygous species, and its modularity provides opportunities to adapt portions of the pipeline to other family types, genotyping technologies or applications. [ABSTRACT FROM AUTHOR]

Vitamin E intake has been implicated in reduction of bladder cancer risk. However, the mechanisms remain elusive. Here we reported that δ-tocotrienol (δ-T3), one of vitamin E isomers, possessed the most potent cytotoxic capacity against human bladder cancer cells, compared with other Vitamin E isomers. δ-T3 inhibited cancer cell proliferation and colonogenicity through induction of G1 phase arrest and apoptosis. Western blotting assay revealed that δ-T3 increased the expression levels of cell cycle inhibitors (p21, p27), pro-apoptotic protein (Bax) and suppressed expression levels of cell cycle protein (Cyclin D1), anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1), resulting in the Caspase-3 activation and cleavage of PARP. Moreover, the δ-T3 treatment inhibited ETK phosphorylation level and induced SHP-1 expression, which was correlated with downregulation of STAT3 activation. In line with this, δ-T3 reduced the STAT3 protein level in nuclear fraction, as well as its transcription activity. Knockdown of SHP-1 partially reversed δ-T3-induced cell growth arrest. Importantly, low dose of δ-T3 sensitized Gemcitabine-induced cytotoxic effects on human bladder cancer cells. Overall, our findings demonstrated, for the first time, the cytotoxic effects of δ-T3 on bladder cancer cells and suggest that δ-T3 might be a promising chemosensitization reagent for Gemcitabine in bladder cancer treatment. [ABSTRACT FROM AUTHOR]

By using entropy and local neighborhood information, we present in this study a robust adaptive Gaussian regularizing Chan–Vese (CV) model to segment the myocardium from magnetic resonance images with intensity inhomogeneity. By utilizing the circular Hough transformation (CHT) our model is able to detect epicardial and endocardial contours of the left ventricle (LV) as circles automatically, and the circles are used as the initialization. In the cost functional of our model, the interior and exterior energies are weighted by the entropy to improve the robustness of the evolving curve. Local neighborhood information is used to evolve the level set function to reduce the impact of the heterogeneity inside the regions and to improve the segmentation accuracy. An adaptive window is utilized to reduce the sensitivity to initialization. The Gaussian kernel is used to regularize the level set function, which can not only ensure the smoothness and stability of the level set function, but also eliminate the traditional Euclidean length term and re-initialization. Extensive validation of the proposed method on patient data demonstrates its superior performance over other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Background: Anomala corpulenta is an important insect pest and can cause enormous economic losses in agriculture, horticulture and forestry. It is widely distributed in China, and both larvae and adults can cause serious damage. It is difficult to control this pest because the larvae live underground. Any new control strategy should exploit alternatives to heavily and frequently used chemical insecticides. However, little genetic research has been carried out on A. corpulenta due to the lack of genomic resources. Genomic resources could be produced by next generation sequencing technologies with low cost and in a short time. In this study, we performed de novo sequencing, assembly and characterization of the antennal transcriptome of A. corpulenta. Results: Illumina sequencing technology was used to sequence the antennal transcriptome of A. corpulenta. Approximately 76.7 million total raw reads and about 68.9 million total clean reads were obtained, and then 35,656 unigenes were assembled. Of these unigenes, 21,463 of them could be annotated in the NCBI nr database, and, among the annotated unigenes, 11,154 and 6,625 unigenes could be assigned to GO and COG, respectively. Additionally, 16,350 unigenes could be annotated in the Swiss-Prot database, and 14,499 unigenes could map onto 258 pathways in the KEGG Pathway database. We also found 24 unigenes related to OBPs, 6 to CSPs, and in total 167 unigenes related to chemodetection. We analyzed 4 OBPs and 3CSPs sequences and their RT-qPCR results agreed well with their FPKM values. Conclusion: We produced the first large-scale antennal transcriptome of A. corpulenta, which is a species that has little genomic information in public databases. The identified chemodetection unigenes can promote the molecular mechanistic study of behavior in A. corpulenta. These findings provide a general sequence resource for molecular genetics research on A. corpulenta. [ABSTRACT FROM AUTHOR]

The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China. A large-scale national survey we conducted on HIV-1 strains among MSM in 11 provinces in China from 2008 to 2013 (n = 920) identified a novel transmission cluster consisting of six strains (0.7%) that belonged to a new circulating recombinant form (designated CRF59_01B). CRF59_01B contains two subtype B segments of U.S.-European origin (in the pol and vpu-env regions) in a CRF01_AE backbone. CRF59_01B is the second CRF (after CRF55_01B) circulating primarily among MSM in China. CRF59_01B occurs at a low frequency (less than 1%), but it was detected in four different provinces/regions in China: Liaoning (northeast China) (n = 3); Hunan (central China) (n = 1); Guangdong (south China) (n = 1); Yunnan (southwest China) (n = 1). One additional recombinant strain was detected in a heterosexual individual in Liaoning province but is not the focus of this paper. Bayesian molecular clock analyses indicate that CRF59_01B emerged as a result of recombination between CRF01_AE and subtype B around the year 2001. The emergence of multiple forms of recombinants and CRFs reflects the ever-increasing contribution of homosexual transmission in China's HIV epidemic and indicates an active HIV transmission network among MSM in China. [ABSTRACT FROM AUTHOR]

Unless the targeted mesh is developable, metric distortion is inevitable during the process of surface mesh parameterization, thus one important objective of all involved parametric studies is to reduce the metric distortion. In order to further reduce area and angle distortion, a novel method of boundary-free mesh parameterization is presented in the paper. Firstly, the initial boundary-fixed conformal parameterization from 3D surface mesh patch to a plane is performed in the method. Then, based on the initial parameterization, the iterations of boundary-free quasi-harmonic parameterization are developed, where the tensor field is updated in each iterative step and the principal curvature direction is utilized to terminate the iteration. The solution of the novel method is convenient to calculate since it involves a series of linear systems. In our novel parameterization method, lower metric distortion and considerable efficiency have been obtained in experiments. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cardiovascular disease (CVD) risk factors in adults with overweight and obesity. Methods: Twenty-two articles were included by searching six databases, the total number of subjects was 620 in these articles. Outcomes were synthesised using a random-effects meta-analysis of the Standardized mean difference (SMD) in CVD risk factors. Results: HIIT and MICT resulted in statistically significant reductions in Weight, BMI, fat%, total cholesterol(TC), and improvement in VO2max. Compared with MICT, subgroup of durations of HIIT training interval ≥2 min can significantly increase VO2max (SMD = 0.444, 95% CI:0.037~0.851,P = 0.032), subgroup of energy expenditure of HIIT equal to MICT can significantly increase VO2max (SMD = 0.399, 95% CI:0.106~0.692,P = 0.008). Conclusions: HIIT appears to provide similar benefits to MICT for improving body composition, VO2maxand TC, but HIIT spent less time than MICT by 9.7 min on one session. HIIT is superior to MICT in improving cardiopulmonary fitness when durations of HIIT training interval ≥2 min or energy expenditure of HIIT same as MICT. PROSPERO ID: CRD42016045835. [ABSTRACT FROM AUTHOR]

Numerous data mining models have been proposed to construct computer-aided medical expert systems. Bayesian network classifiers (BNCs) are more distinct and understandable than other models. To graphically describe the dependency relationships among clinical variables for thyroid disease diagnosis and ensure the rationality of the diagnosis results, the proposed k-dependence causal forest (KCF) model generates a series of submodels in the framework of maximum spanning tree (MST) and demonstrates stronger dependence representation. Friedman test on 12 UCI datasets shows that KCF has classification accuracy advantage over the other state-of-the-art BNCs, such as Naive Bayes, tree augmented Naive Bayes, and k-dependence Bayesian classifier. Our extensive experimental comparison on 4 medical datasets also proves the feasibility and effectiveness of KCF in terms of sensitivity and specificity. [ABSTRACT FROM AUTHOR]

The correspondence of a stack of planar contours in ICT (industrial computed tomography)-based reverse engineering, a key step in surface reconstruction, is difficult when the contours or topology of the object are complex. Given the regularity of industrial parts and similarity of the inter-layer contours, a specialized shape-based inter-layer contours correspondence method for ICT-based reverse engineering was presented to solve the above problem based on the vectorized contours. In this paper, the vectorized contours extracted from the slices consist of three graphical primitives: circles, arcs and segments. First, the correspondence of the inter-layer primitives is conducted based on the characteristics of the primitives. Second, based on the corresponded primitives, the inter-layer contours correspond with each other using the proximity rules and exhaustive search. The proposed method can make full use of the shape information to handle industrial parts with complex structures. The feasibility and superiority of this method have been demonstrated via the related experiments. This method can play an instructive role in practice and provide a reference for the related research. [ABSTRACT FROM AUTHOR]

Breast cancer is recognized as a major public health problem in developing countries; however, there is very little evidence of behavioral factors associated with breast cancer risk. This study was conducted to identify lifestyles as risk factors for breast cancer among Central African women. A case-control study was conducted with 174 cases confirmed histologically by the pathology unit of the National Laboratory and 348 age-matched controls. Data collection tools included a questionnaire with interviews and medical records of patients. Data were analyzed using SPSS software version 20. Odd ratio (OR) and 95% confidence intervals (95% CI) were obtained by unconditional logistic regression. In total, 522 women were studied with a mean age of 45.8 (SD = 13.4) years. By unconditional logistic regression model, women with breast cancer were more likely to have attained illiterate and elementary education level [11.23 (95% CI, 4.65–27.14) and 2.40 (95% CI, 1.15–4.99)], married [2.09 (95% CI, 1.18–3.71)], positive family history [2.31 (95% CI, 1.36–3.91)], radiation exposure [8.21 (95% CI, 5.04–13.38)], consumption charcuterie [10.82 (95% CI, 2.39–48.90)], fresh fish consumption [4.26 (95% CI, 1.56–11.65)], groundnut consumption [6.46 (95% CI, 2.57–16.27)], soybean consumption [16.74 (95% CI, 8.03–39.84)], alcohol [2.53 (95% CI, 1.39–4.60)], habit of keeping money in bras[3.57 (95% CI, 2.24–5.69)], overweight [5.36 (95% CI, 4.46–24.57)] and obesity [3.11(95% CI, 2.39–20.42)]. However, decreased risk of breast cancer was associated with being employed [0.32 (95% CI, 0.19–0.56)], urban residence [0.16 (95% CI, 0.07–0.37)], groundnut oil consumption [0.05 (95% CI, 0.02–0.14)], wine consumption [0.16 (95% CI, 0.09–0.26)], non habit of keeping cell phone in bras [0.56 (95% CI, 0.35–0.89)] and physical activity [0.71(95% CI, 0.14–0.84)]. The study showed that little or no education, marriage, positive family history of cancer, radiation exposure, charcuterie, fresh fish, groundnut, soybean, alcohol, habit of keeping money in bras, overweight and obesity were associated with breast cancer risk among Central African women living in Bangui. Women living in Bangui should be more cautious on the behavioral risk associated with breast cancer. [ABSTRACT FROM AUTHOR]

Gastric intestinal metaplasia (GIM) is a precancerous lesion of the stomach. The detection of GIM using conventional white-light endoscopy (WLE) is difficult. In this study, we determined whether acetic acid-enhanced narrow band imaging (AA-NBI) improves the detection of GIM. A consecutive cohort of 132 individuals aged 40 years or older was subjected to upper gastrointestinal endoscopy using WLE, NBI and AA-NBI. The ability of the three methods to diagnose GIM in patients was compared. Histological assessment (per-patient and per-biopsy) was used for the accuracy assessment. Sixty-six (50.0%) out of the 132 individuals examined were found to have GIM, of which 44 (66.7%) were diagnosed correctly by NBI (sensitivity 66.7% and specificity 68.2%) and 58 (87.9%) were correctly identified by AA–NBI (sensitivity 87.9% and specificity 68.2%), as compared to only 22 (33.3%) by WLE (sensitivity 33.3% and specificity 28.8%). Therefore, the sensitivity of AA–NBI in the diagnosis of GIM was significantly higher than NBI (p<0.05) and WLE (p < 0.001). Our study indicates that AA-NBI can improve the accuracy of endoscopy-targeted biopsies for GIM. [ABSTRACT FROM AUTHOR]

Phosphorylation is catalyzed by protein kinases and is irreplaceable in regulating biological processes. Identification of phosphorylation sites with their corresponding kinases contributes to the understanding of molecular mechanisms. Mass spectrometry analysis of phosphor-proteomes generates a large number of phosphorylated sites. However, experimental methods are costly and time-consuming, and most phosphorylation sites determined by experimental methods lack kinase information. Therefore, computational methods are urgently needed to address the kinase identification problem. To this end, we propose a new kernel-based machine learning method called Supervised Laplacian Regularized Least Squares (SLapRLS), which adopts a new method to construct kernels based on the similarity matrix and minimizes both structure risk and overall inconsistency between labels and similarities. The results predicted using both Phospho.ELM and an additional independent test dataset indicate that SLapRLS can more effectively identify kinases compared to other existing algorithms. [ABSTRACT FROM AUTHOR]

In this study, we aimed to predict newly diagnosed patient responses to antiepileptic drugs (AEDs) using resting-state functional magnetic resonance imaging tools to explore changes in spontaneous brain activity. We recruited 21 newly diagnosed epileptic patients, 8 drug-resistant (DR) patients, 11 well-healed (WH) patients, and 13 healthy controls. After a 12-month follow-up, 11 newly diagnosed epileptic patients who showed a poor response to AEDs were placed into the seizures uncontrolled (SUC) group, while 10 patients were enrolled in the seizure-controlled (SC) group. By calculating the amplitude of fractional low-frequency fluctuations (fALFF) of blood oxygen level-dependent signals to measure brain activity during rest, we found that the SUC patients showed increased activity in the bilateral occipital lobe, particularly in the cuneus and lingual gyrus compared with the SC group and healthy controls. Interestingly, DR patients also showed increased activity in the identical cuneus and lingual gyrus regions, which comprise Brodmann’s area 17 (BA17), compared with the SUC patients; however, these abnormalities were not observed in SC and WH patients. The receiver operating characteristic (ROC) curves indicated that the fALFF value of BA17 could differentiate SUC patients from SC patients and healthy controls with sufficient sensitivity and specificity prior to the administration of medication. Functional connectivity analysis was subsequently performed to evaluate the difference in connectivity between BA17 and other brain regions in the SUC, SC and control groups. Regions nearby the cuneus and lingual gyrus were found positive connectivity increased changes or positive connectivity changes with BA17 in the SUC patients, while remarkably negative connectivity increased changes or positive connectivity decreased changes were found in the SC patients. Additionally, default mode network (DMN) regions showed negative connectivity increased changes or negative changes with BA17 in the SUC patients. The abnormal increased in BA17 activity may be a key point that plays a substantial role in facilitating seizure onset. [ABSTRACT FROM AUTHOR]

Background: Public hospitals deliver over ninety percent of all outpatient and inpatient services in China. Their quality is graded into three levels (A, B, and C) largely based on structural resources, but empirical evidence on the quality of process and outcome of care is extremely scarce. As expectations for quality care rise with higher living standards and cost of care, such evidence is urgently needed and vital to improve care and to inform future health reforms. Methods: We compiled and analyzed a multicenter database of over 4 million inpatient discharge summary records to provide a comprehensive assessment of the level and variations in clinical outcomes of hospitalization at 39 tertiary hospitals in Beijing. We assessed six outcome measures of clinical quality: in-hospital mortality rates (RSMR) for AMI, stroke, pneumonia and CABG, post-procedural complication rate (RS-CR), and failure-to-rescue rate (RS-FTR). The measures were adjusted for pre-admission patient case-mix using indirect standardization method with hierarchical linear mixed models. Results: We found good overall quality with large variations by hospital and condition (mean/range, in %): RSMR-AMI: 6.23 (2.37–14.48), RSMR-stroke: 4.18 (3.58–4.44), RSMR-pneumonia: 7.78 (7.20–8.59), RSMR-CABG: 1.93 (1.55–2.23), RS-CR: 11.38 (9.9–12.88), and RS-FTR: 6.41 (5.17–7.58). Hospital grade was not significantly associated with any risk-adjusted outcome measures. Conclusions: Going to a higher grade public hospital does not always lead to better patient outcome because hospital grade only contains information about hospital structural resources. A hospital report card with some outcome measures of quality would provide valuable information to patients in choosing providers, and for regulators to identify gaps in health care quality. Reducing the variations in clinical practice and patient outcome should be a focus for policy makers in the next round of health sector reforms in China. [ABSTRACT FROM AUTHOR]

PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Focal segmental glomerulosclerosis (FSGS) lesions are similar in characteristics to S lesions of the Oxford classification of IgA nephropathy (IgAN) and may predict poor prognosis. In the present study, we aimed to explore the association between plasma soluble urokinase receptor (suPAR) levels and S lesions and podocytes damage in IgAN patients. Methods: We enrolled 569 IgAN patients with follow-up data and detected plasma suPAR levels at renal biopsy by enzyme-linked immunosorbent assay. Results: Plasma suPAR levels in IgAN patients with or without S lesions did not differ significantly (P = 0.411). However, suPAR levels were positively correlated with proteinuria (r = 0.202, P < 0.001), and negatively correlated with estimated glomerular filtration rate (eGFR, r = –0.236, P < 0.001). In the partial correlation to adjust for eGFR, plasma suPAR levels remained positively correlated with proteinuria (r = 0.112, P = 0.023). In a Cox proportional hazards model, higher levels of plasma suPAR were not associated with poor renal outcome. Plasma suPAR levels of IgAN and primary FSGS patients with nephrotic syndrome were not significantly different (P = 0.306). Plasma suPAR levels in patients with extensive effacement of the epithelial cell foot processes of glomerular podocytes were significantly higher than those with segmental effacement on the basis of comparable eGFR (P = 0.036). Conclusions: In IgAN patients, plasma suPAR levels were not associated with S lesions. However, they were positively associated with proteinuria and negatively associated with eGFR. In addition, plasma suPAR levels were positively associated with the effacement degree of the foot processes, which might partially contribute to the development of proteinuria in patients with IgAN. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease. [ABSTRACT FROM AUTHOR]

Background: After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Complement factor H (CFH) is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression. Methods: A total of 351patients with IgAN participated in this study. They were followed up for an average of 51.8±26.6 months. Renal outcome was defined as a composite endpoint, that included instances of end-stage renal disease (ESRD),≥ 50% decline in estimated glomerular filtration rate (eGFR) or doubling of plasma creatinine levels. Urinary CFH levels were measured by enzyme-linked immunosorbent assay and calculated as the ratio of urinary CFH over creatinine (uCFH/uCr). Results: In the whole cohort, uCFH/uCr values were associated with disease progression either as continuous [log(uCFH/uCr)] or categorical traits (dichotomous and quartile variables) after adjusting for eGFR, proteinuria, mean arterial blood pressure, histological grading and immunosuppressive therapy in the Cox proportional hazard model. Kaplan-Meier analysis showed that higher uCFH/uCr values at baseline predicted worse renal outcome during follow-up (log-rank, P<0.001). Receiver operating characteristic curve (ROC) analysis showed that log(uCFH/uCr) had predictive value for renal outcome (area under curve [AUC]=0.745), and the AUC increased to 0.805 after being incorporated into baseline eGFR and proteinuria. In subgroup analysis with eGFR≥60 mL/min/1.73m2, log(uCFH/uCr) had better predictive value (AUC= 0.724, P=0.002) for renal outcome compared to eGFR (AUC = 0.582, P=0.259) and proteinuria (AUC = 0.615, P=0.114). Conclusions: Urinary CFH levels are associated with renal function decline and increased urinary CFH levels are a risk factor for progression of IgA nephropathy. [ABSTRACT FROM AUTHOR]

Background: Tumor single nucleotide polymorphism (SNP) array is a common platform for investigating the cancer genomic aberration and the functionally important altered genes. Original SNP array signals are usually corrupted by noise, and need to be de-convoluted into absolute copy number profile by analytical methods. Unfortunately, in contrast with the popularity of tumor Affymetrix SNP array, the methods that are specifically designed for this platform are still limited. The complicated characteristics of noise in signals is one of the difficulties for dissecting tumor Affymetrix SNP array data, as they inevitably blur the distinction between aberrations and create an obstacle for the copy number aberration (CNA) identification. Results: We propose a tool named TAFFYS for comprehensive analysis of tumor Affymetrix SNP array data. TAFFYS introduce a wavelet-based de-noising approach and copy number-specific signal variance model for suppressing and modelling the noise in signals. Then a hidden Markov model is employed for copy number inference. Finally, by using the absolute copy number profile, statistical significance of each aberration region is calculated in term of different aberration types, including amplification, deletion and loss of heterozygosity (LOH). The result shows that copy number specific-variance model and wavelet de-noising algorithm fits well with the Affymetrix SNP array signals, leading to more accurate estimation for diluted tumor sample (even with only 30% of cancer cells) than other existed methods. Results of examinations also demonstrate a good compatibility and extensibility for different Affymetrix SNP array platforms. Application on the 35 breast tumor samples shows that TAFFYS can automatically dissect the tumor samples and reveal statistically significant aberration regions where cancer-related genes locate. Conclusions: TAFFYS provide an efficient and convenient tool for identifying the copy number alteration and allelic imbalance and assessing the recurrent aberrations for the tumor Affymetrix SNP array data. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine whether hypoxia preconditioning could improve therapeutic effects of adipose derived mesenchymal stem cells (AMSCs) for diabetes induced erectile dysfunction (DED). AMSCs were pretreated with normoxia (20% O2, N-AMSCs) or sub-lethal hypoxia (1% O2, H-AMSCs). The hypoxia exposure up-regulated the expression of several angiogenesis and neuroprotection related cytokines in AMSCs, including vascular endothelial growth factor (VEGF) and its receptor FIK-1, angiotensin (Ang-1), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). DED rats were induced via intraperitoneal injection of streptozotocin (60 mg/kg) and were randomly divided into three groups—Saline group: intracavernous injection with phosphate buffer saline; N-AMSCs group: N-AMSCs injection; H-AMSCs group: H-AMSCs injection. Ten rats without any treatment were used as normal control. Four weeks after injection, the mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured. The contents of endothelial, smooth muscle, dorsal nerve in cavernoursal tissue were assessed. Compared with N-AMSCs and saline, intracavernosum injection of H-AMSCs significantly raised ICP and ICP/MAP (p<0.05). Immunofluorescent staining analysis demonstrated that improved erectile function by MSCs was significantly associated with increased expression of endothelial markers (CD31 and vWF) (p<0.01) and smooth muscle markers (α-SMA) (p<0.01). Meanwhile, the expression of nNOS was also significantly higher in rats receiving H-AMSCs injection than those receiving N-AMSCs or saline injection. The results suggested that hypoxic preconditioning of MSCs was an effective approach to enhance their therapeutic effect for DED, which may be due to their augmented angiogenesis and neuroprotection. [ABSTRACT FROM AUTHOR]

Venenum Bufonis, a well-known traditional Chinese medicine, has been widely used in Asia and has gained popularity in Western countries over the last decade. Venenum Bufonis has obvious side effects that have been observed in clinical settings, but few studies have reported on its cardiotoxicity. In this work, the cardiotoxicity of Venenum Bufonis was investigated using a 11H NMR-based metabolomics approach. The 1H NMR profiles of the serum, myocardial extracts and liver extracts of specific-pathogen-free rats showed that Venenum Bufonis produced significant metabolic perturbations dose-dependently with a distinct time effect, peaking at 2 hr after dosing and attenuating gradually. Clinical chemistry, electrocardiographic recordings, and histopathological evaluation provided additional evidence of Venenum Bufonis-induced cardiac damage that complemented and supported the metabolomics findings. The combined results demonstrated that oxidative stress, mitochondrial dysfunction, and energy metabolism perturbations were associated with the cardiac damage that results from Venenum Bufonis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Measures of specific knowledge of coping with pre-hospital stroke symptoms can help educate high-risk patients and family caregivers. This study aimed to develop and validate the Pre-hospital Stroke Symptoms Coping Test (PSSCT). Materials and Methods: Reliability and validity were analyzed using multiple data sources. The Delphi expert consultation method was applied to assess the test’s surface validity and content validity index. The final edition of the 19-item PSSCT contained 3 sections assessing coping with typical symptoms and symptoms associated with vomiting and twitching. Its psychometric properties were investigated in a community sample of 300 high-risk patients and family members. Results: The PSSCT was readily accepted by participants. It demonstrated adequate surface validity and content validity, and good internal consistency (KR20 = 0.822) and test-retest reliability (0.769), with difficulty (P) and degree of differentiation (D) ranges of 0.28–0.83 and 0.15–0.66, respectively. It was also able to distinguish between individuals who had/had not experienced a stroke. Experienced individuals scored significantly higher overall and on coping with typical symptoms and twitching (P<0.01). Conclusions: The PSSCT can practically and directly assess critical knowledge regarding coping with pre-hospital stroke symptoms and has good reliability and validity. [ABSTRACT FROM AUTHOR]

Objectives:To assess the potential immunological and virological effects that result from short-course antiretroviral treatment during primary HIV infection (PHI). And to investigate whether treatment initiation time, treatment duration and follow-up time after treatment interruption would affect these post-treatment immunovirological outcomes. Methods:We systematically searched PubMed, Cochrane Library (to September 2013) and retrieved conference abstracts for studies regarding effects of early treatment during PHI on CD4 count and viral load (VL). Using the method of calculating weighted mean differences with Stata11.0, we conducted meta-analyses on the effect of early treatment on CD4 count and VL. Then we performed subgroup analyses by follow-up time after treatment interruption, treatment initiation time and treatment duration. Baseline immunovirological characteristics were also analyzed to account for potential bias. Results:Compared to the untreated arm, treatment during PHI not only increased CD4 count by 85.92 cells/μl but also lowered viral load by 0.30 log copies/ml within one year after treatment interruption. However, the benefits declined gradually, reaching no significance 12-24 months after treatment interruption. Baseline immunovirological characteristics and sensitivity analyses of randomized controlled trials indicated that the benefits mentioned above were underestimated. Extending treatment duration beyond 12 months did not increase efficacy. Conclusions:Short-course treatment during PHI was associated with immunological and virological benefits which last for at least one year after treatment interruption. The conclusions from our study would help the decision-making in the clinical management of PHI. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerotic plaque in rabbit model. The abdominal aortas of thirty-six male New Zealand rabbits were damaged by balloon expansion and the animals were then fed a high fat diet for 12 weeks. Twenty-seven plaques on the near aortic wall were detected using conventional ultrasound examination. The maximum thickness of each plaque was recorded. CEUS was performed on these 27 plaques and the time-intensity curves (TICs) were analyzed offline. Using the quantitative ACQ software, features such as the arrival time (AT), time to peak (TTP), baseline intensity (BI), peak intensity (PI) and enhanced intensity (EI) (EI = PI-BI) were assessed. Inter- and intra-observer agreement of EI were assessed using the Bland-Altman test. After CEUS examination, the rabbits were sacrificed for pathological examination and CD34 monoclonal antibody immunohistochemical detection. Microvessel density (MVD) was counted under the microscope. The relationship between indexes of CEUS and the level of MVD was analyzed. There was a good positive linear correlation between EI and MVD (γ = 0. 854, P<0. 001), the intraclass correlations for inter- and intra-observer agreement for EI were 0.73 and 0.82 respectively, suggesting that EI may be act as a useful index for plaque risk stratification in animal models. [ABSTRACT FROM AUTHOR]