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ObjectiveLow serum adiponectin level can predict hypertension development, and adiponectin gene (ADIPOQ) polymorphisms have been reported to be linked with hypertension risk. Whereas, the interaction between ADIPOQ polymorphisms and environmental factors on the susceptibility of hypertension remained unclear. The purpose of this study was to explore the relationship of ADIPOQ polymorphisms with hypertension risk and their interaction with lipid levels in coal miners.MethodsA matched case-control study with 296 case-control pairs was performed in a large coal mining group located in North China. The participants were questioned by trained interviewers, and their ADIPOQ genotype and lipid levels were determined. Logistic regression, stratified analysis, and crossover analysis were applied to evaluate the effects of rs2241766, rs1501299, and rs266729 genotypes and gene-lipid interaction on hypertension risk.ResultsIn this matched case-control study, the genotypes of rs2241766 TG+GG, rs1501299 GT+TT, and rs266729 CG+GG were marginally related to hypertension risk. Individuals with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level were susceptible to hypertension (TC: odds ratio [OR] = 1.807, 95% confidence intervals [95%CI] = 1.266-2.581; LDL-C: OR = 1.981, 95%CI = 1.400-2.803; HDL-C: OR = 1.559, 95%CI = 1.093-2.223). Antagonistic interactions were detected between rs2241766 and TC, rs1501299 and TC, rs2241766 and LDL-C, and rs1501299 and HDL-C (rs2241766 and TC: OR = 0.393, 95%CI = 0.191-0.806; rs1501299 and TC: OR = 0.445, 95%CI = 0.216-0.918; rs2241766 and LDL-C: OR = 0.440, 95%CI = 0.221-0.877; rs1501299 and HDL-C: OR = 0.479, 95%CI = 0.237-0.967). Stratified analysis showed that hypertension risk was high for the subjects with rs2241766 TG+GG or rs1501299 GG under the low lipid level but low for those under the high lipid level. In the case group, the TC and LDL-C levels for rs2241766 TG+GG were lower than those for rs2241766 GG, and the TC and HDL-C levels for rs1501299 GT+TT were higher than those for rs1501299 GG.ConclusionsAlthough the effects of ADIPOQ polymorphisms alone were not remarkable, an antagonistic interaction was observed between ADIPOQ polymorphisms and lipid levels.

To address the problems of high overflow rate of pipe network inspection well and low drainage efficiency, a rainwater control optimization design approach based on a self-organizing feature map neural network model (SOFM) was proposed in this paper. These problems are caused by low precision parameter design in various rainwater control measures such as the diameter of the rainwater pipe network and the green roof area ratio. This system is to be combined with the newly built rainwater pipe control optimization design project of China International Airport in Daxing District of Beijing, China. Through the optimization adjustment of the pipe network parameters such as the diameter of the rainwater pipe network, the slope of the pipeline, and the green infrastructure (GI) parameters such as the sinking green area and the green roof area, reasonable control of airport rainfall and the construction of sustainable drainage systems can be achieved. This research indicates that compared with the result of the drainage design under the initial value of the parameter, the green roof model and the conceptual model of the mesoscale sustainable drainage system, in the case of a hundred-year torrential rainstorm, the overflow rate of pipe network inspection wells has reduced by 36% to 67.5%, the efficiency of drainage has increased by 26.3% to 61.7%, which achieves the requirements for reasonable control of airport rainwater and building a sponge airport and a sustainable drainage system.

ObjectiveThe American College of Critical Care Medicine recommends that children with persistent fluid, catecholamine, and hormone-resistant septic shock be considered for extracorporeal membrane oxygenation (ECMO) support. Current national estimates of ECMO use in hospitalized children with sepsis are unknown. We sought to examine the use of ECMO in these children and to examine the overall outcomes such as in-hospital mortality, length of stay (LOS), and hospitalization charges (HC).MethodsA retrospective analysis of the National Inpatient Sample, which approximates a 20% stratified sample of all discharges from United States community hospitals, was performed. All children (≤ 17 years) who were hospitalized for sepsis between 2012 and 2014 were included. The associations between ECMO and outcomes were examined by multivariable linear and logistic regression models.ResultsA total of 62,310 children were included in the study. The mean age was 4.2 years. ECMO was provided to 415 of the children (0.67% of the cohort with sepsis). Comparative outcomes of sepsis in children who received ECMO versus those who did not included in-hospital mortality rate (41% vs 2.8%), mean HC ($749,370 vs $90,568) and mean LOS (28.8 vs 9.1 days). After adjusting for confounding factors, children receiving ECMO had higher odds of mortality (OR 11.15, 95% CI 6.57-18.92, p < 0.001), longer LOS (6.6 days longer, p = 0.0004), and higher HC ($510,523 higher, p < 0.0001).ConclusionsUse of ECMO in children with sepsis is associated with considerable resource utilization but has 59% survival to discharge. Further studies are needed to examine the post discharge and neurocognitive outcomes in survivors.

BACKGROUND:Over 90% of outpatient care in China was delivered at public hospitals, making outpatient experience in this setting an important aspect of quality of care. OBJECTIVE:To assess outpatient experience with different aspects of physician services at China's public hospitals and its association with overcrowding of the hospital outpatient departments. RESEARCH DESIGN:Retrospective analysis of a large survey of outpatient experience in Shanghai, China. We tested the hypotheses that patient experience was poorer with physician-patient communication, education, and shared decision-making and where and when there was greater overcrowding of the hospital outpatient departments. Ordered logistic models were estimated separately for general and specialty hospitals. SUBJECTS:7,147 outpatients at 40 public hospitals in Shanghai, China, in 2014. MEASURES:Patient experience with physician services were self-reported based on 12 questions as part of a validated instrument. Indicators of overcrowding included time of visit (morning vs. afternoon, Monday vs. rest of the week) and hospital outpatient volume in the first half of 2014. RESULTS:Overall, patients reported very favorable experience with physician services. Two out of the 12 questions pertaining to both communication and shared decision-making consistently received lower ratings. Hospitals whose outpatient volumes were in the top two quartiles received lower patient ratings, but the relationship achieved statistical significance among specialty hospitals only. CONCLUSIONS:Inadequate physician-patient communication and shared decision-making and hospital overcrowding compromise outpatient experience with physician services at Chinese public hospitals. Effective diversion of patients with chronic and less complex conditions to community health centers will be critical to alleviate the extreme workloads at hospitals with high patient volumes and, in turn, improve patient experience.

Fatty acid desaturases are enzymes that introduce double bonds into fatty acyl chains. Extensive studies of fatty acid desaturases have been done in many plants. However, less is known about the diversity of this gene family in peanut (Arachis hypogaea L.), an important oilseed crop that is cultivated worldwide.In this study, twelve novel AhFADs genes were identified and isolated from peanut. Quantitative real-time PCR analysis indicated that the transcript abundances of AhFAB2-2 and AhFAD3-1 were higher in seeds than in other tissues examined, whereas the AhADS and AhFAD7-1 transcripts were more abundant in leaves. AhFAB2-3, AhFAD3-2, AhFAD4, AhSLD-4, and AhDES genes were highly expressed in flowers, whereas AhFAD7-2, AhSLD-2, and AhSLD-3 were expressed most strongly in stems. During seed development, the expressions of AhFAB2-2, AhFAD3-1, AhFAD7-1, and AhSLD-3 gradually increased in abundance, reached a maximum expression level, and then decreased. The AhFAB2-3, AhFAD3-2, AhFAD4, AhADS, and AhDES transcript levels remained relatively high at the initial stage of seed development, but decreased thereafter. The AhSLD-4 transcript level remained relatively low at the initial stage of seed development, but showed a dramatic increase in abundance at the final stage. The AhFAD7-2 and AhSLD-2 transcript levels remained relatively high at the initial stage of seed development, but then decreased, and finally increased again. The AhFAD transcripts were differentially expressed following exposure to abiotic stresses or abscisic acid. Moreover, the functions of one AhFAD6 and four AhSLD genes were confirmed by heterologous expression in Synechococcus elongates or Saccharomyces cerevisiae.The present study provides valuable information that improves understanding of the biological roles of FAD genes in fatty acid synthesis, and will help peanut breeders improve the quality of peanut oil via molecular design breeding.

Stress is a significant factor in the etiology of depression. Stellate ganglion block (SGB) has been shown to maintain the stability of the autonomic system and to affect the neuroendocrine system, including the hypothalamic-pituitary-adrenal (HPA) axis. The objective of this study was to determine the antidepressant-like effects of SGB on the autonomic system and the HPA axis, apoptosis-related proteins, related spatial learning and memory impairment, and sensorimotor dysfunction.Forty-eight Sprague Dawley rats were assigned to four experimental groups: control + saline (sham group), control + SGB (SGB group), unpredictable chronic mild stress (UCMS) + saline (UCMS group), and UCMS + SGB (UCSG group). Stress-induced effects and the function of SGB were assessed using measures of body weight, coat state, sucrose consumption, and behavior in open-field and Y-maze tests. Neuronal damage was assessed histologically using the hematoxylin-eosin (HE) staining method, while western blotting was used to investigate changes in the expression of apoptosis-related proteins. Plasma corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), corticosterone (CORT), noradrenaline and adrenaline were measured to evaluate changes in the autonomic system and HPA axis.SGB treatment significantly improved sensorimotor dysfunction and spatial learning and memory impairment following UCMS. Moreover, UCMS significantly decreased body weight, sucrose preference and anti-apoptotic protein Bcl-2, and increased scores on measures of coat state, adrenal gland weight, levels of CORT, CRF, ACTH, noradrenaline and adrenaline, as well as increased neuronal loss, cell shrinkage, nuclear condensation, and the pro-apoptotic protein Bax. These symptoms were attenuated by treatment with SGB.These findings suggest that SGB can attenuate depression-like behaviors induced by chronic stress. These protective effects appear to be due to an anti-apoptotic mechanism of two stress pathways-the autonomic system and the HPA axis.

Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet) or a low chromium diet (LC, 0.14 mg chromium/kg diet) during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON), while others remained on the same diet (CON-CON, or LC-LC) for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA methylation which is associated with the insulin signaling pathway in the mice livers.

Emerging evidence supports a key role for the gut microbiota in metabolic diseases, including type 2 diabetes (T2D) and obesity. The dipeptidyl peptidase-4 inhibitor vildagliptin is highly efficacious in treating T2D. However, whether vildagliptin can alter the gut microbiome is still unclear. This study aimed to identify whether vildagliptin modifies the gut microbiota structure during T2D treatment. Diabetic Sprague-Dawley (SD) rats were induced by a high-fat diet and streptozotocin injection (HFD/STZ). Diabetic rats were orally administered a low dose of vildagliptin (LV, 0.01 g/kg/d vildagliptin), high dose of vildagliptin (HV, 0.02 g/kg/d vildagliptin), or normal saline for 12 weeks. Fasting blood glucose, blood glucose after glucose loading, and serum insulin levels were significantly reduced in the LV and HV groups compared with those in the T2D group. The serum GLP-1 level increased more in the vildagliptin-treated group than in the T2D group. Pyrosequencing of the V3-V4 regions of 16S rRNA genes revealed that vildagliptin significantly altered the gut microbiota. The operational taxonomic units (OTUs) and community richness (Chao1) index were significantly reduced in the vildagliptin and diabetic groups compared with those in the control group. At the phylum level, a higher relative abundance of Bacteroidetes, lower abundance of Firmicutes, and reduced ratio of Fimicutes/Bacteroidetes were observed in the vildagliptin-treated group. Moreover, vildagliptin treatment increased butyrate-producing bacteria, including Baceroides and Erysipelotrichaeae, in the diabetic rats. Moreover, Lachnospira abundance was significantly negatively correlated with fasting blood glucose levels. In conclusion, vildagliptin treatment could benefit the communities of the gut microbiota.

BACKGROUND:As a regulator essential for many cell cycle-related proteins, the robust expression of Cell cycle-Related and Expression-elevated Protein in Tumor (CREPT) implicates a poor diagnosis of endoderm and mesoderm-derived tumors. Whether CREPT plays the same role in the tumorigenesis derived from ectodermal tissues remains elusive. METHODS:To explore the role of CREPT in ectoderm-derived tumors, cells from 7oral squamous cell carcinoma (OSCC) lines and 84clinical OSCC samples were exploited in this study. Quantitative PCR, Western blot assay and immunohistochemistry were applied in the evaluation of CREPT, cyclin D1 and c-Myc expression. Knocking-down of CREPT was performed by lentivirus delivering specific shRNA of CREPT. The effects of CREPT on OSCC were examined by cell proliferation, colony formation, apoptosis, cell migration and xenograft implantation experiments. RESULTS:Compared with human normal oral keratinocytes, OSCC cell lines showed a significantly elevated expression of CREPT in both mRNA and protein levels. Consistently, samples from OSCC patients also exhibited a noticeably stronger CREPT expression than the noncancerous samples. In contrast, knocking down of CREPT in OSCC cell lines significantly reduced proliferation, colony formation and migration as well as the expression of cyclin D1 and c-Myc, but promoted apoptosis. Statistical analysis also suggested that CREPT expression was significantly correlated with the T and N classification of OSCC. Furthermore, CAL27 mouse xenograft model confirmed that down-regulation of CREPT prohibited cyclin D1 and c-Myc expression, through which decreased the in vivo tumor growth, but increased the survival ratio of hosts. CONCLUSION:In OSCC cell lines, up-regulated CREPT expression enhanced cell proliferation, migration and cell cycle as well as promoted cyclin D1 and c-Myc expression as it did in endoderm and mesoderm-origin tumors. Our study strongly suggests that CREPT could be used as a marker for the OSCC prognosis and might work as a potential target in future OSCC therapy.

Salt stress has some remarkable influence on chrysanthemum growth and productivity. To understand the molecular mechanisms associated with salt stress and identify genes of potential importance in cultivated chrysanthemum, we carried out transcriptome sequencing of chrysanthemum. Two cDNA libraries were generated from the control and salt-treated samples (Sample_0510_control and Sample_0510_treat) of leaves. By using the Illumina Solexa RNA sequencing technology, 94 million high quality sequencing reads and 161,522 unigenes were generated and then we annotated unigenes through comparing these sequences to diverse protein databases. A total of 126,646 differentially expressed transcripts (DETs) were identified in leaf. Plant hormones, amino acid metabolism, photosynthesis and secondary metabolism were all changed under salt stress after the complete list of GO term and KEGG enrichment analysis. The hormone biosynthesis changing and oxidative hurt decreasing appeared to be significantly related to salt tolerance of chrysanthemum. Important protein kinases and major transcription factor families involved in abiotic stress were differentially expressed, such as MAPKs, CDPKs, MYB, WRKY, AP2 and HD-zip. In general, these results can help us to confirm the molecular regulation mechanism and also provide us a comprehensive resource of chrysanthemum under salt stress.

To evaluate comparative renal functional preservation, perioperative and oncologic outcomes, and complications of thermal ablation (TA) versus partial nephrectomy (PN) in management of Small renal masses (SRMs) in solitary kidney.Medline, Embase, Web of Science and the Cochrane Library were systematically searched. A meta-analysis for comparative studies comparing TA with PN was performed. According to predefined inclusion criteria, seven datasets were identified from 8 observational studies including a total of 628 patients. Cumulated data showed the changes of creatinine (p=0.02) and estimated glomerular filtration rate (eGFR) (p

In human pathological conditions, the acidification of local environment is a frequent feature, such as tumor and inflammation. As the pH of microenvironment alters, the functions of immune cells are about to change. It makes the extracellular acidification a key modulator of innate immunity. Here we detected the impact of extracellular acidification on neutrophil apoptosis and functions, including cell death, respiratory burst, migration and phagocytosis. As a result, we found that under the acid environment, neutrophil apoptosis delayed, respiratory burst inhibited, polarization augmented, chemotaxis differed, endocytosis enhanced and bacteria killing suppressed. These findings suggested that extracellular acidification acts as a key regulator of neutrophil apoptosis and functions.

Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection.To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers.In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis.The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor "a determinant" and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.

To assess the relationships between the risk factors and the incidence of nonfatal occupational injury of coal mine workers of Shanxi Province.A cross-sectional study was conducted from July 2013 to December 2013, and 4319 workers were recruited from more than 200,000 coal mine employees who are exposed to continuous potential risk of occupational injuries by using a two-stage stratified cluster sampling method. Trained interviewers having necessary medical knowledge conducted face-to-face interviews with the participants. Univariate and multivariable logistic regression models were used to estimate the odds ratio (OR) and the 95% confidence interval (CI).A total number of 3618 effective respondents were got from 4319 participants (83.77%) and the mean age of the participants was 41.5 years with the standard deviation of 8.65. Significant crude odds ratios were observed for all factors considered except for marital status, education, work duration, BMI, EPQ-RSC(P) scale and EPQ-RSC(L) scale. Results from multivariable logistic regression model showed significant adjusted odds ratios for risk factors including gender (female vs male 0.275, 0.094-0.800), age (≥55 vs ≤25yr 0.169, 0.032-0.900), work type (light physical labor vs heavy physical labor 0.504, 0.328-0.774), workplace (underground auxiliary vs underground front-line 0.595, 0.385-0.919), length of shiftwork experience (0~5yr vs no shift 2.075, 1.287-3.344 and ≥15yr vs no shift 2.076, 1.230-3.504) and EPQ-RSC(E) score (extraversion vs introversion 0.538, 0.334-0.867).Several risk factors of nonfatal occupational injury were identified including male, age, heavy physical labor, underground front-line, length of shiftwork experience and introversion. The coal mining enterprises should pay attention to controlling the hazards associated with frontline physical work. Workers' behaviors, life styles and personality traits should also be considered, so that the enterprises could set achievable targets for workers and lessen the exposed period to the risky underground workstation.

Diacylglycerol acyltransferase (DGAT) catalyzes the final and only committed acylation step in the synthesis of triacylglycerols. In this study, three novel AhDGATs genes were identified and isolated from peanut. Quantitative real-time RT-PCR analysis indicated that the AhDGAT1-2 transcript was more abundant in roots, seeds, and cotyledons, whereas the transcript abundances of AhDGAT1-1 and AhDGAT3-3 were higher in flowers than in the other tissues examined. During seed development, transcript levels of AhDGAT1-1 remained relatively low during the initial developmental stage but increased gradually during later stages, peaking at 50 days after pegging (DAP). Levels of AhDGAT1-2 transcripts were higher at 10 and 60 DAPs and much lower during other stages, whereas AhDGAT3-3 showed higher expression levels at 20 and 50 DAPs. In addition, AhDGAT transcripts were differentially expressed following exposure to abiotic stresses or abscisic acid. The activity of the three AhDGAT genes was confirmed by heterologous expression in a Saccharomyces cerevisiae TAG-deficient quadruple mutant. The recombinant yeasts restored lipid body formation and TAG biosynthesis, and preferentially incorporated unsaturated C18 fatty acids into lipids. The present study provides significant information useful in modifying the oil deposition of peanut through molecular breeding.

Plant health and soil fertility are affected by plant-microbial interactions in soils. Peanut is an important oil crop worldwide and shows considerable adaptability, but growth and yield are negatively affected by continuous cropping. In this study, 16S rRNA gene clone library analyses were used to study the succession of soil bacterial communities under continuous peanut cultivation. Six libraries were constructed for peanut over three continuous cropping cycles and during its seedling and pod-maturing growth stages. Cluster analyses indicated that soil bacterial assemblages obtained from the same peanut cropping cycle were similar, regardless of growth period. The diversity of bacterial sequences identified in each growth stage library of the three peanut cropping cycles was high and these sequences were affiliated with 21 bacterial groups. Eight phyla: Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Gemmatimonadetes, Planctomycetes, Proteobacteria and Verrucomicrobia were dominant. The related bacterial phylotypes dynamic changed during continuous cropping progress of peanut. This study demonstrated that the bacterial populations especially the beneficial populations were positively selected. The simplification of the beneficial microbial communities such as the phylotypes of Alteromonadales, Burkholderiales, Flavobacteriales, Pseudomonadales, Rhizobiales and Rhodospirillales could be important factors contributing to the decline in peanut yield under continuous cropping. The microbial phylotypes that did not successively changed with continuous cropping, such as populations related to Rhizobiales and Rhodospirillales, could potentially resist stress due to continuous cropping and deserve attention. In addition, some phylotypes, such as Acidobacteriales, Chromatiales and Gemmatimonadales, showed a contrary tendency, their abundance or diversity increased with continuous peanut cropping progress. Some bacterial phylotypes including Acidobacteriales, Burkholderiales, Bdellovibrionales, and so on, also were affected by plant age.

p300 is a well-known histone acetyltransferase (HAT) and coactivator that plays vital roles in many physiological processes. Despite extensive research on the involvement of p300 in the regulation of transcription in numerous cell lines, the roles of this protein in regulating pluripotency genes and odontogenic differentiation in human dental pulp cells (HDPCs) are poorly understood. To address this issue, we investigated the expression of OCT4, NANOG and SOX2 and the proliferation and odontogenic differentiation capacity of HDPCs following p300 overexpression. We found that p300 overexpression did not overtly affect the ability of HDPCs to proliferate. The overexpression of p300 upregulated the promoter activity and the mRNA and protein expression of NANOG and SOX2. The HAT activity of p300 appeared to partially mediate the regulation of these factors; indeed, when a mutant form of p300 lacking the HAT domain was overexpressed, the promoter activity and expression of NANOG and SOX2 decreased relative to p300 overexpression but was greater than in the control. Furthermore, we demonstrated that the mRNA levels of the odontogenic marker genes dentine matrix protein-1 (DMP-1), dentin sialophosphoprotein (DSPP), dentin sialoprotein (DSP), osteopontin (OPN) and osteocalcin (OCN) were significantly decreased in HDPCs overexpressing p300 cultured under normal culture conditions and increased in HDPCs inducted to undergo odontogenic differentiation. This finding was further confirmed by measuring levels of alkaline phosphatase (ALP) activity and assessing the formation of mineralized nodules. The HAT activity of p300 had no significant effect on odontogenic differentiation. p300 was recruited to the promoter regions of OCN and DSPP and might be acting as a coactivator to increase the acetylation of lysine 9 of histone H3 of OCN and DSPP. Collectively, our results show that p300 plays an important role in regulating the expression of key pluripotency genes in HDPCs and modifying odontogenic differentiation.

Our previous study showed that the patients with more metabolic risk factors had higher risk of high ankle-brachial index (ABI), but the relationship between high ABI and the risk of severe cardiovascular and cerebrovascular diseases is still under debate. This study aims to evaluate this association in the general population. 1486 subjects of South China were recruited in the study. 61 subjects were defined as high ABI group (ABI≥1.3) and 65 subjects were randomly selected as normal ABI group (0.9

OBJECTIVES: Behavioral interventions are effective strategies for HIV/AIDS prevention and control. However, implementation of such strategies relies heavily on the accurate estimation of the high-risk population size. The multiplier method and generalized network scale-up method were recommended to estimate the population size of those at high risk for HIV by UNAIDS/WHO in 2003 and 2010, respectively. This study aims to assess and compare the two methods for estimating the size of populations at high risk for HIV, and to provide practical guidelines and suggestions for implementing the two methods. METHODS: Studies of the multiplier method used to estimate the population prevalence of men who have sex with men in China published between July 1, 2003 and July 1, 2013 were reviewed. The generalized network scale-up method was applied to estimate the population prevalence of men who have sex with men in the urban district of Taiyuan, China. RESULTS: The median of studies using the multiplier method to estimate the population prevalence of men who have sex with men in China was 4-8 times lower than the national level estimate. Meanwhile, the estimate of the generalized network scale-up method fell within the range of national level estimate. CONCLUSIONS: When high-quality existing data are not readily available, the multiplier method frequently yields underestimated results. We thus suggest that the generalized network scale-up method is preferred when sampling frames for the general population and accurate demographic information are available.

Cdc7-Dbf4 kinase or DDK (Dbf4-dependent kinase) is required to initiate DNA replication by phosphorylating and activating the replicative Mcm2-7 DNA helicase. DDK is overexpressed in many tumor cells and is an emerging chemotherapeutic target since DDK inhibition causes apoptosis of diverse cancer cell types but not of normal cells. PHA-767491 and XL413 are among a number of potent DDK inhibitors with low nanomolar IC50 values against the purified kinase. Although XL413 is highly selective for DDK, its activity has not been extensively characterized on cell lines. We measured anti-proliferative and apoptotic effects of XL413 on a panel of tumor cell lines compared to PHA-767491, whose activity is well characterized. Both compounds were effective biochemical DDK inhibitors but surprisingly, their activities in cell lines were highly divergent. Unlike PHA-767491, XL413 had significant anti-proliferative activity against only one of the ten cell lines tested. Since XL413 did not effectively inhibit DDK in multiple cell lines, this compound likely has limited bioavailability. To identify potential leads for additional DDK inhibitors, we also tested the cross-reactivity of ∼400 known kinase inhibitors against DDK using a DDK thermal stability shift assay (TSA). We identified 11 compounds that significantly stabilized DDK. Several inhibited DDK with comparable potency to PHA-767491, including Chk1 and PKR kinase inhibitors, but had divergent chemical scaffolds from known DDK inhibitors. Taken together, these data show that several well-known kinase inhibitors cross-react with DDK and also highlight the opportunity to design additional specific, biologically active DDK inhibitors for use as chemotherapeutic agents.

BACKGROUND: Germin-like superfamily members are ubiquitously expressed in various plant species and play important roles in plant development and defense. Although several GLPs have been identified in peanut (Arachis hypogaea L.), their roles in development and defense remain unknown. In this research, we study the spatiotemporal expression of AhGLPs in peanut and their functions in plant defense. RESULTS: We have identified three new AhGLP members (AhGLP3b, AhGLP5b and AhGLP7b) that have distinct but very closely related DNA sequences. The spatial and temporal expression profiles revealed that each peanut GLP gene has its distinct expression pattern in various tissues and developmental stages. This suggests that these genes all have their distinct roles in peanut development. Subcellular location analysis demonstrated that AhGLP2 and 5 undergo a protein transport process after synthesis. The expression of all AhGLPs increased in responding to Aspergillus flavus infection, suggesting AhGLPs' ubiquitous roles in defense to A. flavus. Each AhGLP gene had its unique response to various abiotic stresses (including salt, H2O2 stress and wound), biotic stresses (including leaf spot, mosaic and rust) and plant hormone stimulations (including SA and ABA treatments). These results indicate that AhGLPs have their distinct roles in plant defense. Moreover, in vivo study of AhGLP transgenic Arabidopsis showed that both AhGLP2 and 3 had salt tolerance, which made transgenic Arabidopsis grow well under 100 mM NaCl stress. CONCLUSIONS: For the first time, our study analyzes the AhGLP gene expression profiles in peanut and reveals their roles under various stresses. These results provide an insight into the developmental and defensive roles of GLP gene family in peanut.

Mammaglobin A (MGBA) is a novel breast cancer-associated antigen almost exclusively over-expressed in primary and metastatic human breast cancers, making it a potential therapeutic target for breast cancer. The development of dendritic cell (DC)-induced tumor antigen specific CD8(+) cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. In this study we constructed recombinant replication-defective adenoviral (Ad) vectors encoding MGBA and evaluated their ability to trigger anti-tumor immunity in vitro. DCs were isolated from the human peripheral blood monocyte cells (PBMCs) of two HLA-A33(+) healthy female volunteers, and infected with adenovirus carrying MGBA cDNA (Ad-MGBA). After that, the Ad-MGBA-infected DCs were used to stimulate CD8(+) CTLs in vitro and the latter was used for co-culture with breast cancer cell lines. The data revealed that infection with Ad-MGBA improved DC maturation and up-regulated the expression of co-stimulatory molecules and the secretion of interleukin-12 (IL-12), but down-regulated interleukin-10 (IL-10) secretion from DCs. Ad-MGBA-infected DC-stimulated CD8(+)CTLs displayed the highest cytotoxicity towards HLA-A33(+)/MGBA(+) breast cancer MDA-MB-415 cells compared with other CD8(+)CTL populations, and compared with the cytotoxicity towards HLA-A33(-)/MGBA(+) breast cancer HBL-100 cells and HLA-A33(-)/MGBA(-) breast cancer MDA-MB 231 cells. In addition, Ad-MGBA-infected DC-stimulated CD8(+) CTLs showed a high level of IFNγ secretion when stimulated with HLA-A33(+)/MGBA(+) breast cancer MDA-MB-415 cells, but not when stimulated with HLA-A33(-)/MGBA(+) HBL-100 and HLA-A33(-)/MGBA(-)MDA-MB-231 cells. In addition, killing of CD8(+)CTLs against breast cancer was in a major histocompability complex (MHC)-limited pattern. Finally, the data also determined the importance of TNF-α in activating DCs and T cells. These data together suggest that MGBA recombinant adenovirus-infected DCs could induce specific anti-tumor immunity against MGBA(+) breast cancers, which could provide a novel strategy in the immunotherapy of breast cancer.

HIV-1 DNA in blood monocytes is considered a viral source of various HIV-1 infected tissue macrophages, which is also known as "Trojan horse" hypothesis. However, whether these DNA can produce virions has been an open question for years, due to the inability of isolating high titer and infectious HIV-1 directly from monocytes.In this study, we demonstrated successful isolation of two strains of M-HIV-1 (1690 M and 1175 M) from two out of four study subjects, together with their in vivo controls, HIV-1 isolated from CD4+ T-cells (T-HIV-1), 1690 T and 1175 T. All M- and T- HIV-1 isolates were detected CCR5-tropic. Both M- HIV-1 exhibited higher levels of replication in monocyte-derived macrophages (MDM) than the two T- HIV-1. Consistent with our previous reports on the subject 1175 with late infection, compartmentalized env C2-V3-C3 sequences were identified between 1175 M and 1175 T. In contrast, 1690 M and 1690 T, which were isolated from subject 1690 with relatively earlier infection, showed homogenous env C2-V3-C3 sequences. However, multiple reverse transcriptase (RT) inhibitor resistance-associated variations were detected in the Gag-Pol region of 1690 M, but not of 1690 T. By further measuring HIV DNA intracellular copy numbers post-MDM infection, 1690 M was found to have significantly higher DNA synthesis efficiency than 1690 T in macrophages, indicating a higher RT activity, which was confirmed by AZT inhibitory assays.These results suggested that the M- and T- HIV-1 are compartmentalized in the two study subjects, respectively. Therefore, we demonstrated that under in vitro conditions, HIV-1 infected human monocytes can productively release live viruses while differentiating into macrophages.

Peanut is an important oil crop worldwide and shows considerable adaptability but growth and yield are negatively affected by continuous cropping. Soil micro-organisms are efficient bio-indicators of soil quality and plant health and are critical to the sustainability of soil-based ecosystem function and to successful plant growth. In this study, 18S rRNA gene clone library analyses were employed to study the succession progress of soil eukaryotic micro-organisms under continuous peanut cultivation. Eight libraries were constructed for peanut over three continuous cropping cycles and its representative growth stages. Cluster analyses indicated that soil micro-eukaryotic assemblages obtained from the same peanut cropping cycle were similar, regardless of growth period. Six eukaryotic groups were found and fungi predominated in all libraries. The fungal populations showed significant dynamic change and overall diversity increased over time under continuous peanut cropping. The abundance and/or diversity of clones affiliated with Eurotiales, Hypocreales, Glomerales, Orbiliales, Mucorales and Tremellales showed an increasing trend with continuous cropping but clones affiliated with Agaricales, Cantharellales, Pezizales and Pyxidiophorales decreased in abundance and/or diversity over time. The current data, along with data from previous studies, demonstrated that the soil microbial community was affected by continuous cropping, in particular, the pathogenic and beneficial fungi that were positively selected over time, which is commonplace in agro-ecosystems. The trend towards an increase in fungal pathogens and simplification of the beneficial fungal community could be important factors contributing to the decline in peanut growth and yield over many years of continuous cropping.

Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells. We posit FTY720 can induce an anergy-polarized phenotype switch on DCs in vitro, especially upon endotoxic activation. A lipopolysaccharide (LPS)-induced mouse bone marrow-derived dendritic cell (BMDC) activation model was employed to test FTY720-induced phenotypic changes on immature and mature DCs. Specifically, methods for morphology, nanostructure, cytokine production, phagocytosis, endocytosis and specific antigen presentation studies were used. FTY720 induced significant alterations of surface markers, as well as decline of shape indices, cell volume, surface roughness in LPS-activated mature BMDCs. These phenotypic, morphological and topographical changes were accompanied by FTY720-mediated down-regulation of proinflammatory cytokines, including IL-6, TNF-α, IL-12 and MCP-1. Together with suppressed nitric oxide (NO) production and CCR7 transcription in FTY720-treated BMDCs with or without LPS activation, an inhibitory mechanism of NO and cytokine reciprocal activation was suggested. This implication was supported by the impaired phagocytotic, endocytotic and specific antigen presentation abilities observed in the FTY720-treated BMDCs. In conclusion, we demonstrated FTY720 can induce anergy-polarization in both immature and LPS-activated mature BMDCs. A possible mechanism is FTY720-mediated reciprocal suppression on the intrinsic activation pathway and cytokine production with endpoint exhibitions on phagocytosis, endocytosis, antigen presentation as well as cellular morphology and topography.

Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer's disease (AD). Pharmacological inhibition of this kinase may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in AD. Here we test the ability of harmine, and numerous additional β-carboline compounds, to inhibit the DYRK1A dependent phosphorylation of tau protein on serine 396, serine 262/serine 356 (12E8 epitope), and threonine 231 in cell culture assays and in vitro phosphorylation assays. Results demonstrate that the β-carboline compounds (1) potently reduce the expression of all three phosphorylated forms of tau protein, and (2) inhibit the DYRK1A catalyzed direct phosphorylation of tau protein on serine 396. By assaying several β-carboline compounds, we define certain chemical groups that modulate the affinity of this class of compounds for inhibition of tau phosphorylation.

HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system's microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease.MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species.These observations provide unique insights into glial crosstalk during disease by supporting astrocyte-mediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery and therapeutics that may influence the course of HIV-1-mediated neurodegeneration.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients is common. Neuromuscular Electrical Stimulation (NMES) is a powerful exercise training that may relieve muscle dysfunction in COPD. This study investigated whether electrical stimulation may have atypical adaptations via activation of miRNA related pathways in counteracting COPD muscle dysfunction. Forty-eight male Sprague-Dawley rats were randomly assigned to 3 groups. With the exception of the rats in the control group, the experimental rats were exposed to chronic intermittent hypoxia-hypercapnia (CIHH) (9~11%O2,5.5~6.5%CO2) for 2 or 4 weeks. Electrical stimulation was performed immediately after each CIHH session. Following assessment of the running capacity, biopsy samples were obtained from the gastrocnemius of the rats. The miR-1, miR-133a and miR-133b levels were measured, as well as their related proteins: phosphorylation of Akt (p-AKT), PGC-1alpha (PGC-1α), histone deacetylase 4 (HDAC4) and serum response factor (SRF). Myosin heavy chainlla (MHClla) and myosin heavy chainllb (MHCllb) were also measured to assess fiber type changes. After 2 weeks, compared with the controls, only miR-1 and miR-133a were significantly increased (p<0.05) in the exposure group. After 4 weeks, the exposure group exhibited a decreased running distance (p = 0.054) and MHClla-to-MHCllb shift (p<0.05). PGC-1α (p = 0.051), nuclear HDAC4 (p = 0.058), HDAC4, p-AKT, PGC-1α and SRF was also significantly decreased (p<0.05). In contrast, miR-1 and miR-133a were significantly increased (p<0.05). Four weeks of electrical stimulation can partly reversed those changes, and miR-133b exhibited a transient increase after 2 weeks electrical stimulation. Our study indicate miRNAs may have roles in the response of CIHH-impaired muscle to changes during electrical stimulation. [ABSTRACT FROM AUTHOR]