Abscisic acid (ABA) is the most important hormone for plants to resist drought and other abiotic stresses. ABA binds directly to the PYR/PYL family of ABA receptors, resulting in inhibition of type 2C phosphatases (PP2C) and activation of downstream ABA signaling. It is envisioned that intervention of ABA signaling by small molecules could help plants to overcome abiotic stresses such as drought, cold and soil salinity. However, chemical instability and rapid catabolism by plant enzymes limit the practical application of ABA itself. Here we report the identification of a small molecule ABA mimic (AM1) that acts as a potent activator of multiple members of the family of ABA receptors. In Arabidopsis, AM1 activates a gene network that is highly similar to that induced by ABA. Treatments with AM1 inhibit seed germination, prevent leaf water loss, and promote drought resistance. We solved the crystal structure of AM1 in complex with the PYL2 ABA receptor and the HAB1 PP2C, which revealed that AM1 mediates a gate-latch-lock interacting network, a structural feature that is conserved in the ABA-bound receptor/PP2C complex. Together, these results demonstrate that a single small molecule ABA mimic can activate multiple ABA receptors and protect plants from water loss and drought stress. Moreover, the AM1 complex crystal structure provides a structural basis for designing the next generation of ABA-mimicking small molecules.
abscisic acid; plant hormone; drought resistance; crystal structure; ABA-mimicking ligand
In the the title compound, C19H18BrNO3, the furanone ring is almost planar [maximum atomic deviation = 0.019 (3) Å] and is nearly perpendicular to the two phenyl rings, making dihedral angles of 88.96 (17) and 87.71 (17)°. Intermolecular C—H⋯O hydrogen bonding is present in the crystal structure.
The title compound, C19H30BrNO5, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dibromo-5-[(S)-l-menthyloxy]furan-2(5H)-one and l-valine in the presence of potassium hydroxide. The molecular structure contains an approximately planar (r.m.s. deviation = 0.0204 Å) five-membered furanone ring and a six-membered menthyloxy ring adopting a chair conformation. The crystal packing is stabilized by intermolecular O—H⋯O and N—H⋯O hydrogen bonding.
The title compound, C19H30ClNO5, was obtained by the tandem asymmetric Michael addition–elimination reaction of (5S)-3,4-dichloro-5-(l-menthyloxy)furan-2(5H)-one and l-valine in the presence of potassium hydroxide. The furanone unit is approximately planar (r.m.s. deviation = 0.0204 Å) and the six-membered cyclohexane ring adopts a chair conformation. The crystal structure is stabilized by a network of O—H⋯O and N—H⋯O hydrogen bonds.
The title compound, C17H26ClNO5, was prepared via a tandem asymmetric Michael addition–elimination reaction of (5S)-3,4-dichloro-5-(l-menthyloxy)furan-2(5H)-one and l-alanine in the presence of potassium hydroxide. The five-membered furanone ring is approximately planar while the six-membered menthyloxy ring adopts a chair conformation. The crystal packing is stabilized by intermolecular O—H⋯O and N—H⋯O hydrogen bonds.
Ixodes scapularis transmits the agent of human granulocytic anaplasmosis, among other pathogens. The mechanisms used by the tick to control Anaplasma phagocytophilum are not known. We demonstrate that the I. scapularis Janus kinase (JAK)–signaling transducer activator of transcription (STAT) pathway plays a critical role in A. phagocytophilum infection of ticks. The A. phagocytophilum burden increases in salivary glands and hemolymph when the JAK-STAT pathway is suppressed by RNA interference. The JAK-STAT pathway exerts its anti-Anaplasma activity presumably through STAT-regulated effectors. A salivary gland gene family encoding 5.3-kDa antimicrobial peptides is highly induced upon A. phagocytophilum infection of tick salivary glands. Gene expression and electrophoretic mobility shift assays showed that the 5.3-kDa antimicrobial peptide–encoding genes are regulated by tick STAT. Silencing of these genes increased A. phagocytophilum infection of tick salivary glands and transmission to mammalian host. These data suggest that the JAK-STAT signaling pathway plays a key role in controlling A. phagocytophilum infection in ticks by regulating the expression of antimicrobial peptides.
Genome-wide association studies (GWAS) are popular for identifying genetic variants which are associated with disease risk. Many approaches have been proposed to test multiple single nucleotide polymorphisms (SNPs) in a region simultaneously which considering disadvantages of methods in single locus association analysis. Kernel machine based SNP set analysis is more powerful than single locus analysis, which borrows information from SNPs correlated with causal or tag SNPs. Four types of kernel machine functions and principal component based approach (PCA) were also compared. However, given the loss of power caused by low minor allele frequencies (MAF), we conducted an extension work on PCA and used a new method called weighted PCA (wPCA). Comparative analysis was performed for weighted principal component analysis (wPCA), logistic kernel machine based test (LKM) and principal component analysis (PCA) based on SNP set in the case of different minor allele frequencies (MAF) and linkage disequilibrium (LD) structures. We also applied the three methods to analyze two SNP sets extracted from a real GWAS dataset of non-small cell lung cancer in Han Chinese population. Simulation results show that when the MAF of the causal SNP is low, weighted principal component and weighted IBS are more powerful than PCA and other kernel machine functions at different LD structures and different numbers of causal SNPs. Application of the three methods to a real GWAS dataset indicates that wPCA and wIBS have better performance than the linear kernel, IBS kernel and PCA.
Clinical studies have shown the evidence that the bladder wall thickness is an effective biomarker for bladder abnormalities. The clinical optical cystoscopy, the current gold standard, cannot show the wall thickness. The use of ultrasound by experts may generate some local thickness information, but the information is limited in field-of-view and is user dependent. Recent advances in magnetic resonance (MR) imaging technologies lead MR-based virtual cystoscopy or MR cystography toward a potential alternative to map the wall thickness for the entire bladder. From a high resolution structural MR volumetric image of the abdomen, a reasonable segmentation of the inner and outer borders of the bladder wall can be achievable. Starting from here, this paper reviews the limitation of a previous distance field-based approach of measuring the thickness between the two borders and then provides a solution to overcome the limitation by an electric field-based strategy. In addition, this paper further investigates a surface fitting strategy to minimize the discretization errors on the voxel-like borders and facilitate the thickness mapping on the three-dimensional patient-specific bladder model. The presented thickness calculation and mapping were tested on both phantom and human subject datasets. The results are preliminary but very promising with a noticeable improvement over the previous distance field-based approach.
Bladder imaging; MR cystography; bladder wall thickness; iso-surface; distance field; electric field; surface fitting; moving least squares
Insulin-like growth factor-1 (IGF1) and its most abundant binding protein, insulin-like growth factor binding protein-3 (IGFBP3), have been implicated in fibrotic lung diseases and persistent acute respiratory distress syndrome (ARDS) because of profibrogenic and antiapoptotic activity. Whether levels of circulating IGF1 and IGFBP3 are altered in ARDS, and whether they predict progression of and survival from ARDS remains unknown. This study aims to characterize circulating levels of IGF1 and IGFBP3 in patients at risk for ARDS in relation to (1) development of ARDS, and (2) mortality among ARDS cases.
In this case-cohort study, consecutive patients with risk factors for ARDS admitted to the intensive care unit (ICU) were enrolled and followed prospectively for development of ARDS. Cases were followed for all-cause mortality through Day 60. Of 2397 patients enrolled in the parent study, plasma samples were available in 531 (22%) patients (356 controls, 175 cases) from early in presentation. Total plasma IGF1 and IGFBP3 were measured.
After adjusting for relevant clinical covariates including severity of illness, IGF1 and IGFBP3 levels were significantly lower in ARDS cases than controls (odds ratio [OR], 0.58; P =0.006; OR, 0.57; P=0.0015, respectively). Among ARDS cases, IGF1 and IGFBP3 levels were significantly lower in the 78 (45%) non-survivors (hazard ratio [HR], 0.70; P =0.024; HR, 0.69; P=0.021, respectively).
Lower levels of circulating IGF1 and IGFBP3 were independently associated with ARDS case status. Furthermore, lower levels were associated with mortality among ARDS cases. This data supports a role of the IGF pathway in ARDS.
Adult Respiratory Distress Syndrome; Insulin-Like Growth Factor-1; Insulin-Like Growth Factor Binding Protein-3; Molecular Epidemiology; Serum Biomarkers
Polygoni Perfoliati Herba is widely used in China with antibacterium, anti-inflammatory, expectorant, antitumor, and antivirus activities. To reveal the mechanisms of the activities of Polygoni Perfoliati Herba, the relationship between the fingerprinting profile and its bioactivities was investigated. In the present study, high-performance liquid chromatographic (HPLC) fingerprinting method was developed. The established method was applied to analyze 51 batches of Polygoni Perfoliati Herba samples collected from different locations or in different harvesting times in China. Chemometrics, including similarity analysis, hierarchical clustering analysis, and principal component analysis, were used to express their similarities. It was found that similarity values of the samples were in the range of 0.432–0.998. The results of analgesic tests indicated that Polygoni Perfoliati Herba could significantly inhibit pain induced by hot plate and acetic acid in mice. The results of anti-inflammatory tests showed that Polygoni Perfoliati Herba had good anti-inflammatory effects (P < 0.01) in two models including dimethyl benzene-induced ear edema and acetic acid-induced peritoneal permeability in mice. Combining the results from chromatographic fingerprints with those from bioactivities, we found that seven peaks from Polygoni Perfoliati Herba were mainly responsible for analgesic and anti-inflammatory activities.
How to resect the caudate lobe safely is a major challenge to current liver surgery which requires further study.
Nine cases (6 hepatic cell carcinoma, 2 cavernous hemangioma and 1 intrahepatic cholangiocacinoma) were performed using the anterior transhepatic approach in the isolated complete caudate lobe resection. During the operation, we used the following techniques: the intraoperative routine use of Peng’s multifunction operative dissector (PMOD), inflow and outflow of hepatic blood control, low central venous pressure and selective use of liver hanging maneuver.
There were no perioperative deaths observed after the operation. The median operating time was 230 ± 43.6 minutes, the median intraoperative blood loss was 606.6 ± 266.3 ml and the median length of postoperative hospital stay was 12.6 ± 2.9 days. The incidence of complications was 22.22% (2/9).
PMOD and “curettage and aspiration” technique can be of great help of in the dissection of vessels and parenchyma, clearly making caudate lobe resection safer, easier and faster.
The aim of the study reported here was to examine health care resource utilization, costs, and risk of rehospitalization for total knee replacement (TKR) patients with and without muscle atrophy/weakness (MAW).
Patients and methods
Individuals aged 50–64 years with commercial insurance or 65+ years with Medicare Supplemental Insurance (Medicare) who had a hospitalization for TKR between January 1, 2006 and September 30, 2009 were identified from a large US claims database. First hospitalization for TKR was defined as the index stay. All patients were classified into three cohorts according to when MAW was diagnosed relative to TKR: pre-MAW, post-MAW, and no MAW. The association between MAW and health care costs over the 12-month post-index period and the probability of rehospitalization were assessed via multivariate regressions
The study sample included 53,696 Medicare and 46,058 commercial insurance TKR patients. Controlling for cross-cohort differences, both the pre- and post-MAW cohorts had significantly higher total health care costs (Medicare US$4,201 and US$9,404 higher, commercial insurance US$2,737 and US$6,640 higher, respectively) than the no MAW cohort (all P < 0.05). The post-MAW cohort in both populations was also more likely to have any all-cause or replacement-related rehospitalization compared with the no MAW cohort.
Among US patients undergoing TKR, those with MAW had higher health care utilization and costs than patients without MAW.
rehospitalization; resource utilization; Medicare; health insurance; USA
The aim of this study was to determine the effects of paracrine regulation on the invasive ability of MCF-7 human breast cancer cells through human adipose-derived stem cell (hADSC) adipogenesis. hADSC differentiation of the third and fourth passages of cells was induced in different induction media: osteogenic, adipogenic and chondrogenic. Transwell migration assays in the differently conditioned media, flow cytometry, enzyme-linked immunosorbent assay and western blot analysis for selected cytokines were performed. The flow cytometric analysis demonstrated positive expression of CD29, CD44 and CD105, while expression of CD34 and CD45 was not identified. The transwell migration assay showed that the invasive ability of MCF-7 cells was significantly enhanced during hADSC adipogenesis. hADSCs exerted a significantly positive effect on the invasive activity of MCF-7 cells during adipo-genesis. The results indicate that the high expression levels of activating protein 2 (aP2) in MCF-7 and adipocytes induced for 12 days may be associated with cell growth, invasion and metastasis. Peroxisome proliferator-activated receptor γ may be involved in fatty syntheses during adipogenic initiation and following adipogenic differentiation, possibly acting as a protection factor resulting in cell maturation and differentiation. This study also demonstrated that the expression of vascular endothelial growth factor was repressed by hADSCs, while that of matrix metalloproteinase-2 and urokinase-type plasminogen activator was increased to a significant level.
human adipose-derived stem cells; human breast cancer cells; paracrine; invasive; cytokine; metalloproteinase
Genetic variation may influence chemotherapy response and overall survival in cancer patients.
We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA).
Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population.
In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients.
Loss of muscle mass and muscle strength are natural consequences of the aging process, accompanied by an increased prevalence of chronic health conditions. Research suggests that in the elderly, the presence of comorbidities may impact the muscle mass/strength relationship. The objectives of this study were to characterize the muscle mass/strength relationship in older adults in the USA and to examine the impact of a variety of comorbidities on this relationship.
Data were obtained from the National Health and Nutrition Examination Survey 1999–2002 databases. Subjects aged 50 years and older were included in the present study. Muscle mass was assessed by height-adjusted appendicular skeleton muscle mass (aASM) in kg/m2, as measured by dual-energy x-ray absorptiometry. Muscle strength was assessed via isokinetic quadriceps strength (IQS) in newton as measured by a dynamometer. The relationship between aASM and IQS was assessed adjusting for age and gender. The effects of a variety of comorbidities on IQS and/or on the relationship between IQS and aASM were assessed using multiple regression models.
This study included 2,647 individuals, with a mean age of 62.6 years and 52.9% of whom were female. The mean (SE) aASM (kg/m2) was 7.3 (0.04), and the mean (SE) IQS (newton) was 365.0 (3.00). After adjusting for age and gender, the correlation coefficient between aASM and IQS was 0.365 (P < 0.001). Diabetes, coronary heart disease/congestive heart failure (CHD/CHF), and vision problems were significant predictors of lower muscle strength (P < 0.05) in the multiple regression models that adjusted for age, gender, and aASM, and obesity significantly modified the relationship between aASM and IQS (P < 0.05).
Among individuals aged 50 and older in the US, muscle mass and muscle strength are positively correlated, independent of the associations of age and gender with muscle mass and strength. A variety of comorbid medical conditions serve as independent predictors of lower muscle strength (e.g., diabetes, CHD/CHF, vision problems) and/or modify the relationship between muscle mass and muscle strength (e.g., obesity).
Muscle mass; Muscle strength; Older adults; Correlation; Comorbidities
Motivation: Metabolic pathways are complex systems of chemical reactions taking place in every living cell to degrade substrates and synthesize molecules needed for life. Modeling the robustness of these networks with respect to the dysfunction of one or several reactions is important to understand the basic principles of biological network organization, and to identify new drug targets. While several approaches have been proposed for that purpose, they are computationally too intensive to analyze large networks, and do not properly handle reversible reactions.
Results: We propose a new model—the flux balance impact degree—to model the robustness of large metabolic networks with respect to gene knock-out. We formulate the computation of the impact of one or several reaction blocking as linear programs, and propose efficient strategies to solve them. We show that the proposed method better predicts the phenotypic impact of single gene deletions on Escherichia coli than existing methods.
firstname.lastname@example.org or Jean-Philippe.Vert@mines.org
Supplementary data are available at Bioinformatics online.
Concentrations of ambient air pollution and pollutants in China have changed considerably during the last decade. However, few studies have evaluated the effects of current ambient air pollution on the health of kindergarten children.
We studied 6730 Chinese children (age, 3–7 years) from 50 kindergartens in 7 cities of Northeast China in 2009. Parents or guardians completed questionnaires that asked about the children’s histories of respiratory symptoms and risk factors. Three-year concentrations of particles with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide (SO2), and nitrogen dioxides (NO2) were calculated at monitoring stations in 25 study districts. A 2-stage regression approach was used in data analyses.
The prevalence of respiratory symptoms was higher among children living near a busy road, those living near chimneys or a factory, those having a coal-burning device, those living with smokers, and those living in a home that had been recently renovated. Among girls, PM10 was associated with persistent cough (odds ratio [OR]PM10 = 1.44; 95% CI, 1.18–1.77), persistent phlegm (ORPM10 = 1.36; 95% CI, 1.02–1.81), and wheezing (ORPM10 = 1.31; 95% CI, 1.04–1.65). NO2 concentration was associated with increased prevalence of allergic rhinitis (OR = 1.96; 95% CI, 1.27–3.02) among girls. In contrast, associations of respiratory symptoms with concentrations of PM10, SO2, and NO2 were not statistically significant among boys.
Air pollution is particularly important in the development of respiratory morbidity among children. Girls may be more susceptible than boys to air pollution.
air pollution; children; respiratory diseases, China
Acute kidney injury (AKI) frequently complicates septic shock and independently predicts mortality in this population. Clinical factors alone do not entirely account for differences in risk of AKI between patients. Genetic variants likely explain this differential susceptibility. To identify genetic variants linked to AKI susceptibility, we conducted a high-density genotyping association study in a large population of patients with septic shock.
Tertiary academic medical center.
1,264 patients with septic shock were analyzed to elucidate clinical risk factors associated with the development of AKI. Among them, 887 Caucasian patients were randomly split into discovery and validation cohorts and genotyped using the Illumina Human CVD BeadChip.
Measurements and Main Results
627 of the 1,264 patients with septic shock and 441 of the 887 patients with genotyping data developed AKI within the first 72 hours of ICU admission. Five single nucleotide polymorphisms (SNPs) were associated with AKI in both the discovery and validation cohorts. Two of these were in the BCL2 gene and both were associated with a decreased risk of AKI (rs8094315: OR 0.61, P=0.0002; rs12457893: OR 0.67, P=0.0002, both for combined data). Bcl-2 is involved in the apoptosis pathway, which has previously been implicated in AKI. Another SNP was in the SERPINA4 gene, whose protein product, kallistatin, has been linked to apoptosis in the kidney.
Large-scale genotyping reveals two SNPs in the BCL2 gene and a SNP in the SERPINA4 gene associated with a decreased risk of developing AKI, supporting the putative role of apoptosis in the pathogenesis of AKI.
acute kidney injury; apoptosis; BCL2; SERPINA4; genetic susceptibility; sepsis
Chemical reduction of graphene oxide (GO) is the main route to produce the mass graphene-based materials with tailored surface chemistry and functions. However, the toxic reducing circumstances, multiple steps, and even incomplete removal of the oxygen-containing groups were involved, and the produced graphenes existed usually as the assembly-absent precipitates. Herein, a substrate-assisted reduction and assembly of GO (SARA-GO) method was developed for spontaneous formation of 3D graphene network on arbitrary conductive substrates including active and inert metals, semiconducting Si, nonmetallic carbon, and even indium-tin oxide glass without any additional reducing agents. The SARA-GO process offers a facile, efficient approach for constructing unique graphene assemblies such as microtubes, multi-channel networks, micropatterns, and allows the fabrication of high-performance binder-free rechargeable lithium-ion batteries. The versatile SARD-GO method significantly improves the processablity of graphenes, which could thus benefit many important applications in sensors and energy-related devices.
This study analyzed administrative claims by a US population with commercial or Medicare supplemental insurance to compare demographics, comorbid medical conditions, and health care utilization and costs among patients undergoing total hip arthroplasty (THA) with and without muscle atrophy/weakness (MAW). Patients were classified into three cohorts: having MAW during the 12 months previous to THA (pre-MAW); having MAW during or over the 12 months after THA (post-MAW); or no MAW claim (no-MAW). In total, 19,607 Medicare and 23,127 commercially insured patients were examined. Controlling for cross-cohort differences, both pre-MAW and post-MAW commercial cohorts had significantly higher total costs ($6,697 and $8,594, in USD respectively) and higher risk of all-cause hospitalization (odds ratios, 1.66 and 1.57, respectively) than the no-MAW cohort (all P < 0.05) during the 1-year follow-up. Similar trends were observed in the Medicare population.
total hip arthroplasty; muscle atrophy; weakness; health care costs; health care utilization
Polygoni Multiflori Caulis, the dried caulis of Polygonum multiflorum Thunb., is one of the commonly used traditional Chinese medicines having antioxidant, anti-obesity, anti-inflammatory and antibacterial effects. Polygoni Multiflori Caulis used clinically or circulated on market have great differences in their diameters. However, to the best of our knowledge, no study has been reported on the qualities of Polygoni Multiflori Caulis with different diameters.
Systematic HPLC/UV/MS chromatographic fingerprinting and quantitative analytical methods combined with principal component analysis were developed and applied to analyze different Polygoni Multiflori Caulis samples. The contents of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, the chemical marker for quality control on Polygoni Multiflori Caulis specified in Chinese Pharmacopoeia (2010 edition), were found to have surprising relevance with the samples’ diameters for the first time.
The finding provides a scientific basis for collecting Polygoni Multiflori Caulis in the best time. Moreover, the diameter can be used as the criterion for quality control on Polygoni Multiflori Caulis as a preliminary step in the future. In addition, scores plot obtained from principal component analysis shows the obvious differences between unqualified Polygoni Multiflori Caulis samples and qualified ones visually, which can be used to single out the unqualified ones with qualified ones efficiently and immediately.
Polygoni Multiflori Caulis; Quality assessment; HPLC/UV/MS; Principle component analysis
We examined the association between household solid fuel exposure and lung function in a densely populated district in urban Shanghai, China.
Spirometry was performed in 12,506 subjects, aged 18 and over, residing the Putuo District in Shanghai, China, in a cross-sectional survey. Exposure to solid fuel use at home was assessed by administered questionnaire, estimating duration and total amount of solid fuel use at home during the lifetime.
After adjusting for confounders, the subjects with exposure to household solid fuel had a 1.3% [95% confidence interval (CI) 0.57 to 2.02] decrease in forced expiratory volume in 1 sec (FEV1) percent predicted and 3.5% (95% CI 2.74 to 4.18) decrease in forced vital capacity (FVC) percent predicted, respectively. Trends towards decreased pulmonary function measures were seen for longer duration and greater amount of household fuel use at home, in the highest compared with lowest tertile (P values for trend < 0.001). We observed decrease in FEV1 and FVC percent predicted across increase in tertile of BMI in association with in-home solid fuel exposure.
This study suggests that in-home solid fuel exposure is associated with reduced lung function in an urban population.
solid fuel; lung function; body mass index; Chinese
Drinking deep seawater (DSW) with high levels of magnesium (Mg) decreased serum lipids in animal studies. Therefore the effects of drinking DSW on blood lipids and its antioxidant capacity in hypercholesterolemic subjects were investigated. DSW was first prepared by a process of filtration and reverse osmosis, and then the concentrated DSW with high levels of Mg was diluted as drinking DSW. Forty-two hypercholesterolemic volunteers were randomly divided into three groups: reverse osmotic (RO) water, DSW (Mg: 395 mg/L, hardness 1410 ppm), and magnesium-chloride fortified (MCF) water (Mg: 386 mg/L, hardness 1430 ppm). The subjects drank 1050 mL of water daily for 6 weeks, and blood samples were collected and analyzed on weeks 0, 3, and 6. Drinking DSW caused a decrease in blood total cholesterol levels and this effect was progressively enhanced with time. Serum low-density lipoprotein–cholesterol (LDL-C) was also decreased by DSW. Further, total cholesterol levels of subjects in the DSW group were significantly lower than those in the MCF water or RO water groups. Compared with week 0, the DSW group had higher blood Mg level on weeks 3 and 6, but the Mg levels were within the normal range in all three groups. DSW consumption also lowered thiobarbituric acid-reactive substances (TBARS) values in serum. In conclusion, DSW was apparently effective in reducing blood total cholesterol and LDL-C, and also in decreasing lipid peroxidation in hypercholesterolemic subjects.
antioxidative; deep seawater; hypocholesterolemic effect; magnesium
B-cell translocation gene 3 (BTG3) is a member of the BTG family which inhibits cell proliferation, metastasis, and angiogenesis, and also regulates cell-cycle progression and differentiation in a variety of cell types. However, there is no study to analyze BTG3 expression in epithelial ovarian carcinoma (EOC). Here, we investigated the expression of BTG3 in EOC carcinogenesis and subsequent progression. BTG3 mRNA expression was detected by real-time RT–PCR in ovarian benign and malignant tumors. The expression of BTG3 protein was examined by immunohistochemistry on tissue microarrays containing ovarian normal tissue, benign and borderline epithelial ovarian tumors, and EOCs. Relationships of BTG3 with both EOC clinicopathology and prognosis were analyzed statistically. The expression of BTG3 protein was also evaluated in ovarian normal tissue, benign tumors, and EOCs by western blot. The BTG3 mRNA expression level was higher in ovarian normal tissue and benign tumors than that in borderline, primary, and metastatic carcinoma (p < 0.05), and was negatively correlated with dedifferentiation and FIGO staging of EOC (p < 0.05). Using western blot, BTG3 protein was found lower in EOCs compared to the normal and benign tumors (p < 0.05), and poorly differentiated EOCs showed lower BTG3 expression than well-differentiated and moderately differentiated EOCs (p < 0.05). Immunohistochemically, BTG3 protein expression was statistically lower in EOCs than normal tissue and benign tumors (p < 0.05). EOC patients with low BTG3 protein expression showed a higher incidence of metastasis (p = 0.020), poor differentiation (p = 0.030), and shorter disease-free time and overall survival time (p < 0.05). By using Cox’s proportional hazard model, BTG3 protein expression and FIGO staging were independent prognostic factors for both disease-free time and overall survival time of EOCs (p < 0.05). It was suggested that down-regulated BTG3 expression might play roles in the pathogenesis and aggressiveness of EOC. BTG3 protein expression may be considered as a good marker to indicate the favorable prognosis of EOCs.
Epithelial ovarian carcinoma; BTG3; Down-regulation; Prognosis; Pathological behavior
There have been few published studies on spirometric reference values for healthy children in China. We hypothesize that there would have been changes in lung function that would not have been precisely predicted by the existing spirometric reference equations. The objective of the study was to develop more accurate predictive equations for spirometric reference values for children aged 9 to 15 years in Northeast China.
Spirometric measurements were obtained from 3,922 children, including 1,974 boys and 1,948 girls, who were randomly selected from five cities of Liaoning province, Northeast China, using the ATS (American Thoracic Society) and ERS (European Respiratory Society) standards. The data was then randomly split into a training subset containing 2078 cases and a validation subset containing 1844 cases. Predictive equations used multiple linear regression techniques with three predictor variables: height, age and weight. Model goodness of fit was examined using the coefficient of determination or the R2 and adjusted R2. The predicted values were compared with those obtained from the existing spirometric reference equations. The results showed the prediction equations using linear regression analysis performed well for most spirometric parameters. Paired t-tests were used to compare the predicted values obtained from the developed and existing spirometric reference equations based on the validation subset. The t-test for males was not statistically significant (p>0.01). The predictive accuracy of the developed equations was higher than the existing equations and the predictive ability of the model was also validated.
We developed prediction equations using linear regression analysis of spirometric parameters for children aged 9–15 years in Northeast China. These equations represent the first attempt at predicting lung function for Chinese children following the ATS/ERS Task Force 2005 guidelines on spirometry standardization.