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Objectives: The identification of structural variants and single‐nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole‐genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. Methods: We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ‐T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES). Results: Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon‐level copy‐number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities. Conclusions: Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, when routine genetic tests have failed to provide a diagnosis. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the relationship between the consumption of plant-based diet and frailty in older Chinese adults. Design: Prospective cohort study Setting: Community-based setting in 22 provinces of China. Participants: The final sample included data from 3990 older adults from 2011–2014 from the Chinese Longitudinal Healthy Longevity Survey Measurements: A plant-based diet index (PDI) was calculated based on a qualitative food frequency questionnaire. Frailty was defined using modified Fried criteria. A Generalized Estimating Equation was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for frailty. We further performed subgroup analyses stratified by sex and lifestyle factors. Results: 557 cases of frailty were observed. After adjustment for covariates, the RR for frailty of a high PDI was 0.792 (95% CI: 0.644–0.973), relative to a low PDI. During follow-up, compared with respondents with a continually low PDI, the respondents with a continually high PDI had a significantly reduced risk of frailty (RR = 0.683, 95% CI: 0.514–0.908). In further subgroup analysis, a consistently high PDI over time resulted in a significantly reduced risk of frailty for male (RR = 0.591, 95% CI: 0.391–0.893); for never smokers (RR = 0.670, 95% CI: 0.458–0.979); for people who did never consume alcohol (RR = 0.654, 95% CI: 0.454–0.941); and for people with current or former exercise habits (RR = 0.488, 95% CI: 0.313–0.762). Conclusion: Plant-based diet was associated with low risk of frailty in men and in older adults with healthy lifestyle. These findings stress that plant-based diet should be recommended as a dietary strategy to prevent and reduce frailty in older adults; in addition, more dietary interventions along with lifestyle modification should be adopted to promote successful ageing, especially for women. [ABSTRACT FROM AUTHOR]

Lithium-based ceramic breeder Li4SiO4 will suffer long-term high temperature during operation. That may lead to changes to its microstructure, chemical phase, composition elements, and further impacts its mechanical performance and hydrogen isotope release behavior. In the present work, long-term annealing at 900 °C in He incl. 0.1 vol% H2 flow atmosphere for designated times was conducted. Li4SiO4 pebbles with poor or excellent mechanical performance (abbr. "poor pebbles" and "excellent pebbles") have porous or dense microstructure, respectively. Coarsening process that grains and pores get larger as a function of annealing time was observed for Li4SiO4 poor pebbles. Li4SiO4 excellent pebbles can maintain its microstructure stability, and only slight grain growth was observed after 1000 h of annealing. Oxygen and lithium element loss was demonstrated over annealing time. Compression tests and Weibull analysis indicate that the distinct degradation of mechanical performance of Li4SiO4 pebbles mainly occur in the initial 100 h of annealing, and then the degradation process slows down. Thermal desorption spectroscopy reveals that 1000 h of annealing caused the disappearance of high temperature release peak (665 °C) and the shift of low temperature release peaks (around 300 °C) to lower temperature. The former is mainly attributed to decomposition of carbon impurities (Li2CO3) and the latter is attributed to carbon impurities and the transition from closed to open pores. [ABSTRACT FROM AUTHOR]

With manufacturing going through the Industry 4.0 revolution, a vast amount of data and information exchange leads to an increase in complexity of digitized manufacturing systems. To tackle such complexity, one solution is to design and operate a digital twin model under different levels of abstraction, with different levels of detail, according to the available information and scope of the model. To support efficient, coherent and stable information flows between models with different levels of detail, a mathematical structure, called a delta lens, has been explored and developed to support rigorous bidirectional transitions between the models. To support different types of abstractions in manufacturing, a hybrid delta lens has been proposed and its formal representation is developed to support the generalization of its structure and properties. Benefits of the proposed hybrid delta lenses are demonstrated through an application to an industrial case to support the modelling of an automatic, high-throughput assembly line. [ABSTRACT FROM AUTHOR]

Based on the high‐speed video records of 54 lightning flashes striking on a cluster of tall buildings in Guangzhou and the return stroke peak currents provided by lightning location systems, this paper analyzed the two‐dimensional (2D) first‐return‐stroke striking distances (SD) of lightning flashes to buildings with a height ranging from 100 to 600 m. Three methods, including one proposed in this study, have been used to estimate the 2D SD. The results with different methods basically agree with each other and show that the height and the top geometry of the structure on which lightning terminates are key factors that affect the SD. The correlation between the SD and the peak return stroke current appeared very scattered, particularly in the cases when each building was considered separately. Besides, we found that: (a) the estimated 2D average initiation speed of upward connecting leader (UCL) on different buildings are similar, ranging from 4.9 to 23 × 104 m/s, with an average of 13.4 × 104 m/s; (b) about 87% (27/31) flashes that struck on buildings with simple top shape only have one upward leader observed, while for buildings with complicated top shape, only 26% (6/23) flash cases have one upward leader observed; (c) for the 36 flashes to four tall buildings with heights higher than 300 m, the 2D average speed ratio of the downward leader and the UCL is 0.74 during the last 0.1 ms before the first return stroke. Key Points: First‐return‐stroke striking distance of 54 lightning flashes to seven tall buildings (heights between 100 and 600 m) was estimatedA new striking distance estimation method, based on the relationship between the length of upward connecting leader and time, was proposedThe height and the top geometry of the structure on which lightning terminates are key factors that affect the striking distances [ABSTRACT FROM AUTHOR]

Tussock swamp meadow, as a typical wetland in Northeast China, is governed by hydrological variations. Understanding the responses of tussocks to environment factors would help in advancing the management, protection and restoration of tussock sedge wetlands. We investigated ecological characteristics of tussocks in coverage, species height and above-biomass along a flooding gradient. Tussock patterning and hummock size were also recorded to identify the mechanisms of self-organization in tussock swamp meadow. Results showed that sampling sites and species had no significant effects on tussock ecological characteristics. Species coverage, species height and biomass were moderately related to flooding depth. The fittings based on Gauss model showed that the optimum flooding depth and flooding proportion for tussock biomass in critical growth period are 11.2 cm and 29.6%, respectively. Species coverage and above-biomass increased with increasing tussock density. Relationships between above-biomass and hummock size accorded with Gauss curve. Linear mixed-effect models indicated that flooding proportion, tussock density and hummock height exert great influences on the growth of tussocks. Results help to advance our understanding of the tussocks' responses to environmental factors and the mechanisms of self-organization in tussock sedge wetlands. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explain the phenomenon of seawater intrusion (SWI) by numerical simulation and analysis. In this paper, a numerical method was introduced for solving the onedimensional advection-dispersion equation by the explicit finite difference method, and the corresponding convergence conditions and the boundary attenuation factor,β, were given, which can be convenient in studying the impact of different influencing factors on seawater intrusion. Additionally, the effects of six hydraulic factors on seawater intrusion were explored under steady state, namely, hydraulic conductivity, longitudinal dispersivity, hydraulic gradient, flux, evaporation and rainfall. Moreover, two different seawater intrusion types were also studied, namely active seawater intrusion and passive seawater intrusion. Meanwhile, the control variates method was adopted to explore the influence of a single factor on seawater invasion. According to the calculated results, with the increase of hydraulic conductivity, longitudinal dispersion, flux and evaporation, the degree of it will be aggravated, but the rainfall can play a role in mitigating seawater intrusion. Besides, under active seawater intrusion conditions, the growth of the numerical value of hydraulic gradient will aggravate seawater intrusion, while under passive seawater intrusion conditions, it will slow down the degree of invasion. All in all, the results and achievements are consistent with the actual situation, which can explain the phenomenon of seawater intrusion. [ABSTRACT FROM AUTHOR]

Whereas groundwater numerical simulation is an essential part of groundwater environmental impact analysis, the authors propose a more accurate and suitable method for identifying and predicting the groundwater environment, laying a scientific basis for groundwater environmental impact evaluation. Targeted at the river and lake connection project in Jilin Province, this paper establishes a groundwater prediction model based on the groundwater modelling system (GMS), and considers the land salinization risk posed by the variation in groundwater level after the water diversion of the project. The results show that the depth of phreatic water in each area is greater than the upper limit of ecological water level after the implementation of the project plan, leaving a small chance for soil salinization. [ABSTRACT FROM AUTHOR]

Tectonic stress is one of the most active deformation factors in the Earth’s crust. Therefore, determinations of its mode of action and form of conversion are critical for guiding research that evaluates preservation conditions in shale gas. Through a survey that targeted many structural features, such as vertical folds and conjugated joints, we investigated the revolution characteristics of the tectonic stress field, the mode of action and the sequence of tectonic stress in the Dingshan region of SE Sichuan by structural analysis methods. Meanwhile, based on a geologic analysis of tectonic stress mechanisms, the structural stress in the region using finite element numerical simulations is quantitatively analyzed. The results show that the region has experienced tectonic stress fields over four different periods and in four different orientations: NW-SE, nearly N-S, nearly E-W and NE-SW. The NW-SE force occurred earlier than that of the nearly N-S force, followed by nearly E-W compression, and finally N-E force. It is concluded that the structural framework of the study area was formed by the effects of the NE-SW compressional stress, which is still active today. The simulation demonstrated that overlapping parts of the intensive strain zone had a higher maximum principal stress, particularly in areas of energy concentration. As for mud and shale, which show excellent sealing capacity, the key to preserving shale gas is the accumulation of energy and a low degree of breakage. Considering the nip-out line of the Longmaxi Formation in the Dingshan region, the buried depth limit of shale-gas production (4500 m), and fault length, the preservation conditions of shale gas and identified favorable targets within the Longmaxi Formation is evaluated. [ABSTRACT FROM AUTHOR]

The article presents a study focusing on the relation between genetic susceptibility to obesity and the risk of developing asthma in Hispanic Americans. Topics discussed include the presence of physician-diagnosed asthma in the patients under study; the calculation of a body mass index (BMI)-based genetic risk score (GRS); and the analysis of BMI-increasing alleles.

We isolated 65 rhizobial strains from faba bean (Vicia faba L.) from Panxi, China, studied their plant growth promoting ability with nitrogen free hydroponics, genetic diversity with clustered analysis of combined ARDRA and IGS-RFLP, and phylogeny by sequence analyses of 16S rRNA gene, three housekeeping genes and symbiosis related genes. Eleven strains improved the plant shoot dry mass significantly comparing to that of not inoculated plants. According to the clustered analysis of combined ARDRA and IGS-RFLP the isolates were genetically diverse. Forty-one of 65 isolates represented Rhizobium anhuiense, and the others belonged to R. fabae, Rhizobium vallis, Rhizobium sophorae, Agrobacterium radiobacter, and four species related to Rhizobium and Agrobacterium. The isolates carried four and five genotypes of nifH and nodC, respectively, in six different nifH-nodC combinations. When looking at the species-nifH-nodC combinations it is noteworthy that all but two of the six R. anhuiense isolates were different. Our results suggested that faba bean rhizobia in Panxi are diverse at species, plant growth promoting ability and symbiosis related gene levels. [ABSTRACT FROM AUTHOR]

Background Brain-derived neurotrophic factor ( BDNF) may play a vital role in the homeostatic regulation of intestinal barrier integrity. We aimed to investigate the physiological role of BDNF in maintaining the intestinal epithelial barrier using postinflammatory irritable bowel syndrome ( PI- IBS) mice and explore the underlying molecular mechanisms using intestinal epithelial cells in vitro. Methods Postinflammatory- IBS mice were induced by intrarectal administration of trinitrobenzene sulfonic acid and allowed to recover for 28 days. Frequency of defecation, fecal water content, colonic epithelial integrity and expressions of BDNF and tight junction ( TJ) proteins (occludin, ZO-1, claudin-1, claudin-2) of the PI- IBS mice were investigated. Based on the results of animal studies, we further performed RT- PCR and Western blots to assess how BDNF stimulation and BDNF knockdown impacted TJ proteins in the ht-29 intestinal epithelial cells. Key Results Water content of stools was significantly increased in the PI- IBS mice compared with controls. Colonic mucosa from the PI- IBS mice displayed epithelial barrier defects and exhibited increased protein expressions of BDNF and claudin-2 and decreased protein expressions of occludin, ZO-1 and claudin-1. Furthermore, a si RNA against BDNF in the ht-29 cells could effectively suppress BDNF gene and protein expressions, and subsequently reduce TJ gene and protein levels. When the ht-29 cells were incubated with different doses of exogenous BDNF, significant increases of occludin, ZO-1 and claudin-1 and decreases of claudin-2 protein were observed. Conclusions & Inferences BDNF may play a role in regulating intestinal epithelial barrier via affecting the expression of TJ proteins. [ABSTRACT FROM AUTHOR]

Alteration of gene expression tightly regulates lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in lipogenesis, catalyzes the conversion of SFA to MUFA, and inhibition of its activity impairs lipid synthesis. As posttranscriptional regulators, microRNAs are involved in many pathways of lipid metabolism; however, their effect on SCD-1 has not been reported. In this study, miR-125b was identified as a potential regulator of SCD-1 using bioinformatics analysis. Here, we validated SCD-1 as the target of miR-125b using a dual luciferase assay. During adipogenesis, a synthetic mimic or inhibitor was used to overexpress or reduce the expression of miR-125b in porcine adipocytes. Overexpression of miR-125b reduced the accumulation of lipid droplets and triglycerides concentration and repressed SCD-1 protein expression and MUFA composition. The inhibitor had the reverse effect. Small interfering RNA against SCD-1 tested in adipocytes further proved the direct correlation between miR-125b and SCD-1. Moreover, in vivo experiments in mice showed that injection of miR-125b expression vector decreased the hepatic triglycerides concentration relative to saline. This study indicated that miR-125b regulates lipogenesis by targeting SCD-1; therefore, miR-125b might be applied in therapy of lipid metabolism disorders. [ABSTRACT FROM AUTHOR]

Previously, a single nucleotide polymorphism ( SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index ( BMI), body fat mass index ( FMI) and waist circumference ( WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI ( n = 169,551; 0.32 kg m−2; 95% CI 0.28-0.32, P < 1 × 10−32), WC ( n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10−32) and FMI ( n = 48,192; 0.17 kg m−2; 0.13-0.22, P = 1.0 × 10−13). Cox proportional hazard regression analyses for mortality showed that the hazards ratio ( HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC ( HR: 1.00; 0.98-1.03, P = 0.662) and for FMI ( HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes. [ABSTRACT FROM AUTHOR]

Background Cancer-associated inflammation is a key molecular feature of pancreatic ductal adenocarcinoma. In this study, we systematically evaluated the prognostic relevance of systemic inflammatory response (SIR) markers in patients with advanced pancreatic cancer. Methods A total of 321 consecutive patients with pathologically-confirmed locally advanced or metastatic pancreatic adenocarcinoma were retrospectively recruited. The patients were divided into a test set (n = 110) and a validation set (n = 211). The associations between overall survival (OS) and clinically available SIR markers including white blood cell (WBC) count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, platelet count, neutrophil-lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio (LMR) were analyzed using Kaplan–Meier curves and multivariate Cox proportional models. Results High WBC count, neutrophil count, monocyte count, NLR, PLR and low LMR were significantly associated with decreased OS in the test set. Using the validation set for confirmation, we found also in multivariate analysis an independent value of WBC count (hazard ratio (HR): 2.176, 95% confidence interval (CI): 1.560–3.035, P < 0.001), neutrophil count (HR: 2.807, 95% CI: 2.000–3.940, P < 0.001), monocyte count (HR: 1.848, 95% CI: 1.315–2.598, P < 0.001), NLR (HR: 2.204, 95% CI: 1.590–3.055, P < 0.001), PLR (HR: 1.537, 95% CI: 1.114–2.122, P = 0.009) and LMR (HR: 0.569, 95% CI: 0.412–0.784, P = 0.001) for OS in patients with advanced pancreatic cancer. Conclusions Our study confirmed that SIR markers can be used to determine optimal therapeutic strategies for individual patients and to predict pancreatic cancer prognosis. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, a tone reservation (TR) method is employed to reduce the peak-to-average power ratio (PAPR) in multi-input multi-output orthogonal frequency division multiplexing systems with space frequency block coding (SFBC). The key idea of the employed TR method is taking signals on multiple transmit antennas into account to design appropriate peak reduction symbols, which can significantly reduce the PAPR of SFBC multi-input multi-output orthogonal frequency division multiplexing signals. With the employed TR scheme, the SFBC structure can be maintained, whereas the traditional TR method would destroy it, resulting in the degradation of bit error rate (BER) performance. Simulation results demonstrate that the employed TR scheme can provide significantly better BER performance than the traditional TR method with slight PAPR reduction degradation. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Merlin, encoded by the Neurofibromatosis 2 (NF2) gene, is a multifunctional tumor suppressor that integrates and regulates extracellular cues and intracellular signaling pathways, both at the plasma membrane and in the nucleus, to control cell proliferation, migration and invasion. Molecular mechanisms regulating merlin's tumor-suppressive activity have not been clearly defined. Here we report that merlin can be sumoylated on Lysine residue (K76) in vitro and in vivo. Sumoylation mediates merlin's intramolecular and intermolecular binding activities and regulates its cytoplasm/nucleus trafficking. Interestingly, sumoylation of merlin is regulated by its phosphorylation via Akt and PAK2 kinases. Mutation of K76 into arginine (R) abolishes its sumoylation, disrupts merlin cortical cytoskeleton residency and attenuates its stability. Using a K76R mutant merlin in a subcutaneous U87MG xenograft model, we demonstrate that merlin sumoylation is required for tumor-suppressive activity. Taken together, our findings indicate that merlin is sumoylated and that this post-translational modification is essential for tumor suppression. [ABSTRACT FROM AUTHOR]

A bioassay-guided fractionation of Cynanchum komarovii crude alkaloid extract led to the isolation of two alkaloids. The isolated alkaloids were identified as 7-demethoxytylophorine (1) and 6-hydroxyl-2,3-dimethoxy phenanthroindolizidine (2) based on the comparison of their spectroscopic characteristics with the literature data. Insecticidal, antifeedant and growth inhibitory effects of these two alkaloids against the 3rd instar larvae of Plutella xylostella L. ( Lepidoptera: Plutellidae) were examined. The results showed that alkaloid 1 was more toxic than alkaloid 2 against the 3rd instar larvae of Plutella xylostella L., but both alkaloids were less toxic than the total alkaloid fraction. For antifeedant activity, alkaloid 1 showed AFC50 of 1.82 mg/ml at 24 h after treatment, alkaloid 2 showed 3.89 mg/ml, while total alkaloids showed 1.56 mg/ml. In dipping toxicity test, alkaloids 1 and 2 produced 93.3% and 63.3% mortality at 72 h after treatment, respectively, while total alkaloids produced 96.7% mortality. The LC50 values for alkaloids 1, 2 and the total alkaloids were 3.54, 9.21 and 2.63 mg/ml, respectively. The development of larvae was also inhibited, and the growth inhibition rates at the concentration of 15.00 mg/ml were 92.8%, 78.2% and 98.6% for alkaloids 1, 2 and total alkaloids, respectively, at 72 h after treatment. Compared with antifeedant and dipping effect, the alkaloids 1, 2 and total alkaloid fraction revealed weak feeding toxicity, and their corrected mortality rates at the concentration of 15.00 mg/ml were 60.0%, 40.0% and 63.3% at 7 days after treatment. The LC50 values for alkaloids 1, 2 and total alkaloids were 12.58, 32.37 and 8.88 mg/ml, respectively, at 7 days after treatment. [ABSTRACT FROM AUTHOR]

Objective:Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids.Design and methods:We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800).Results:After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m−2 greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m−2 greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed.Conclusion:Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits. [ABSTRACT FROM AUTHOR]

The cyclin-dependent kinase 4 (CDK4) amplicon is frequently amplified in numerous human cancers including gliomas. PIKE-A, a proto-oncogene that is one of the important components of the CDK4 amplicon, binds to and enhances the kinase activity of Akt, thereby promoting cancer progression. To define the roles of the PIKE-A/Akt interaction in glioblastoma multiform (GBM) progression, we used biochemical protein/protein interaction (PPI) assays and live cell fluorescence-based protein complementation assays to search for small peptide antagonist from these proteins that were able to block their interaction. Here, we show that disruption of the interaction between PIKE-A and Akt by the small peptides significantly reduces glioblastoma cell proliferation, colony formation, migration and invasion. Disruption of PIKE-A/Akt association potently suppressed GBM cell proliferation and sensitized the cells to two clinical drugs that are currently used to treat GBM. Interestingly, GBM cells containing the CDK4 amplicon were more responsive to the inhibition of the PIKE-A/Akt interaction than GBM cells lacking this amplicon. Taken together, our findings provide proof-of-principle that blocking a PPI that is essential for cancer progression provides a valuable strategy for therapeutic discovery. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902. [ABSTRACT FROM AUTHOR]

Hypertension and type 2 diabetes (T2D) commonly coexist, and both conditions are major risk factors for cardiovascular disease (CVD). We aimed to examine the association between genetic predisposition to high blood pressure and risk of CVD in individuals with T2D. The current study included 1,005 men and 1,299 women with T2D from the Health Professionals Follow-up Study and Nurses' Health Study, of whom 732 developed CVD. A genetic predisposition score was calculated on the basis of 29 established blood pressure-associated variants. The genetic predisposition score showed consistent associations with risk of CVD in men and women. In the combined results, each additional blood pressure-increasing allele was associated with a 6% increased risk of CVD (odds ratio [OR] 1.06 [95% CI 1.03-1.10]). The OR was 1.62 (1.22-2.14) for risk of CVD comparing the extreme quartiles of the genetic predisposition score. The genetic association for CVD risk was significantly stronger in patients with T2D than that estimated in the general populations by a meta-analysis (OR per SD of genetic score 1.22 [95% CI 1.10-1.35] vs. 1.10 [1.08-1.12]; I² = 71%). Our data indicate that genetic predisposition to high blood pressure is associated with an increased risk of CVD in individuals with T2D. [ABSTRACT FROM AUTHOR]

This paper investigates regional hospital efficiency in China. As hospital operations naturally iticrease along with an undesirable output of patient mortality, which may induce medical disputes and ligations, this study adopts data envelopment analysis to evaluate and compare the efficiency scores obtained with and without considering the undesirable output. On the basis of province-level panel data over 2002-2008 and considering the risk-adjusted undesirable output, empirical estimates indicate that hospital efficiency is moderate, but increases gradually from 0.6881 to 0.8159. Importantly, without considering the undesirable output, the average efficiency score is overestimated and the efficiency ranking across provinces changes considerably. An efficiency gap is found between coastal and non-coastal regions, but this gap's drop is mainly contributed by the fast efficiency improvement of the western regions. However, the central regions continue to achieve a significantly lower efficiency score than the eastern and western regions. Moreover, the initiation of the New Rural Cooperative Medical System has overall enhanced hospital efficiency in China, especially for the non-coastal regions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To observe the effects of Dachengqi Decoction (, DCQD) on morphological changes in the network of enteric nerve-interstitial cells of Cajal (ICCs)-smooth muscle cells (SMC) of enteric deep muscular plexuses (DMP) in the rats with multiple organ dysfunction syndrome (MODS). METHODS: One hundred Wistar rats of both sexes weighing 200 to 250 g were randomly divided into the control group, MODS group, and DCQD group. The morphologic changes of enteric nerve-ICC-SMC network in the DMP of intestine was observed using c-Kit and vesicular acetylcholine transporter/neuronal nitric oxide synthase immunohistochemical double-staining with whole-mount preparation technique, confocal laser scanning microscopy, and electron microscopy. RESULTS: Compared with the control group, the distribution and densities of cholinergic/nitrergic nerves and ICC in the DMP (ICC-DMP) of intestine in the MODS group were significantly decreased (P<0.01), and the network of cholinergic nerve-ICC-SMC was disrupted; and the ultrastructural features of ICC-DMP, enteric nerve, and SMC were severely damaged. After treatment with DCQD, the damage in the network of enteric nerve-ICC-SMC was significantly recovered. Compared with the MODS group, the distribution and densities of cholinergic/nitrergic nerves and ICC-DMP in the DCQD group were significantly increased (P<0.01); and the ultrastructural features of ICC-DMP, enteric nerve, smooth muscle cells were significantly recovered. CONCLUSIONS: DCQD can improve the gastrointestinal motility in MODS. The mechanism may be related to the effect of repairing the damages in the network of enteric nerve-ICC-SMC. [ABSTRACT FROM AUTHOR]

ims/hypothesis: The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese. Methods: We genotyped 17 variants in 17 loci in a population-based Han Chinese cohort including 3,210 unrelated individuals. A genetic risk score (GRS) was calculated on the basis of these variants. The discriminatory ability was assessed by the area under the receiver operating characteristics curve. Results: The odds ratio for type 2 diabetes and hyperglycaemia with each GRS point (per risk allele) was 1.18 (95% CI 1.12–1.23, p = 1.3 × 10) and 1.12 (95% CI 1.09–1.16, p = 7.5 × 10), respectively. Compared with participants with GRS ≤11.0 (7.63%), those with GRS ≥19.0 (8.87%) had a 4.58-fold higher risk (95% CI 2.49–8.42) of type 2 diabetes. The GRS also showed a significant association with lower beta cell function estimated by HOMA of beta cell function ( p = 8.4 × 10). In addition, we observed significant interactive effects between GRS and BMI on fasting glucose and HbA levels ( p = 0.04 and p = 0.03 for interaction, respectively). Discrimination of diabetes risk was improved ( p < 0.001) when the GRS was added to a model including clinical risk factors. The AUCs were 0.62 and 0.77, respectively, for the GRS and conventional clinic risk factors alone, and 0.79 when the GRS was added. Conclusions/interpretation: In this Han Chinese population, the GRS of 17 combined variants modestly but significantly improved discrimination of the conventional risk factors for type 2 diabetes. [ABSTRACT FROM AUTHOR]

The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations. The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals ( n = 3,210) and tested for association with risk of type 2 diabetes and related phenotypes. The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73–1.00, p value under an additive model [ p(add)] = 0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77–0.96, p[add] = 0.0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels ( p[add] = 0.0169–5.3 × 10−6), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B ( p[add] = 0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B ( p[add] = 5.8 × 10−5) in the combined analysis. Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity. [ABSTRACT FROM AUTHOR]

Background Fibroblasts from skin lesions generally exhibit the scleroderma phenotype in the early stage of in vitro culture, and act as one of the most important samples to investigate systemic sclerosis. However, not all cell lines from patients show the scleroderma phenotype, and little prospective evidence can be relied on to predict the phenotype of fibroblasts from systemic sclerosis patients. Objective This study aims to find the predictive factors related to fibroblast phenotypes. Methods Fibroblast lines from 15 patients with systemic sclerosis were established through explant culture, with their scleroderma phenotypes being determined by real-time reverse transcription–polymerase chain reaction (RT-PCR) of procollagen transcription. Logistic regression analysis was used to analyse the clinical data of these patients. Haematoxylin–eosin staining was performed to observe histopathological differences. Expression of methylation-related factors was detected by real-time reverse transcription-polymerase chain reaction. Results Eight of the 15 fibroblast cell lines from patients with systemic sclerosis exhibited the scleroderma phenotype. Logistic regression analysis yielded an equation ( Y = –9.718 + 2.525 X1) in which X1 significantly represents the Valentini Disease Activity Index. Histopathology results demonstrated that the scleroderma phenotype was positively correlated with leucocyte infiltration. Further laboratory observations showed increased expression of Dnmt1 in the positive phenotype fibroblasts and a positive correlation between elevations of Dnmt1 and the maintenance period of the scleroderma phenotype. Conclusions The results of this study suggest that the Valentini Disease Activity Index and expression of Dnmt1 may act as indicators of the scleroderma phenotype in fibroblasts. Additionally, these data also imply that epigenetic factors, such as Dnmt1, may be involved in the maintenance of the scleroderma phenotype. Our analyses may be beneficial to the research in systemic sclerosis. Conflicts of interest None declared [ABSTRACT FROM AUTHOR]

The zonal displacement of the western Pacific warm pool (WPWP) and the meridional displacement of the eastern Pacific warm pool (EPWP) and their responses to wind anomalies over the tropical Pacific were investigated. Joint effect of the WPWP and EPWP on ENSO was examined based on a joint effect index, which is a combination of the standardized anomaly time series of the eastern edge of the WPWP and the southern edge of the EPWP. Results show that both WPWP and EPWP are major providers of warm water in the eastern equatorial Pacific. The anomalous eastward extension of the WPWP and abnormal southward extension of the EPWP can supply a large amount of warm water into Nino3 region of the north equator, result in dramatic local SST increase, and trigger El Niño. To the contrary, as scope of the WPWP retreats westward and the EPWP retreats northward, a La Niña will outburst. One cannot separate apart the roles played by the WPWP and EPWP on ENSO, and the joint effect of both warm pools must be considered. A joint index of 1.6 means a new El Niño event is likely to happen. [ABSTRACT FROM AUTHOR]

Three H5N1 influenza viruses were isolated from shell washes of duck and goose eggs confiscated from travelers coming from Vietnam. All eight gene segments of these viruses share high sequence identity with the H5N1 avian influenza viruses that caused outbreaks in poultry and humans in Hong Kong in 1997. Animal studies indicate that these isolated viruses are able to replicate in mouse lung and could be found in the organs of ducks without causing any clinical signs or death. However, the viruses are highly pathogenic for chickens. Although the source of these recently isolated Hong Kong 97-like H5N1 viruses is undetermined, their detection in the egg shell of duck and goose suggests that this particular genotype of H5N1 virus may have re-emerged in nature or may have been circulating continuously. [ABSTRACT FROM AUTHOR]

Research indicates that host age is a determining factor in yeast carriage. From the neonatal period, humans go through several dentition periods, and the emergence and substitution of teeth and changes in living habits greatly change the environment of the oral cavity, and therefore influence colonization by oral commensal organisms, certainly includingCandidaspp. No previous study ofCandidacarriage by different age groups divided by dentition has been reported. This study supplies data on the geographical specificity ofC. albicansgenotypic subgroup distribution.All test individuals came from a single geographical locale over a short period. Following mucosal swab sampling, CHROMagarCandida-yeast differential media were used to determine the frequency of carriage and species. AllC. albicansstrains were confirmed by PCR and PCR using primers reported to span a transposable intron region in the 25S rRNA gene was used to determine genotypic subgroups.The results demonstrate that for the tested population, the frequency ofCandidaspecies and the distribution ofC. albicansgenotypic subgroups varied with age group. With increasing age, the frequency ofC. albicansdecreases, non-C. albicansyeasts increases; Genotypic subgroup A is the dominating strain in the oral cavities of healthy young individuals.The influence of dentition substitution on oral yeast carriage was minor.J Oral Pathol Med(2005)34: 352–6 [ABSTRACT FROM AUTHOR]

CC chemokine receptor 5 (CCR5) is a member of the G-protein-coupled receptor superfamily. It plays an important role in macrophage tropic human immunodeficiency virus-1 entry and in some inflammatory reactions. CCR5-893(–) is a single-nucleotide deletion that results in complete truncation of the C tail of the gene product. We detected CCR5-893(–) in a sample of patients infected with non-tuberculosis mycobacteria and found that it was maintained heterozygously with a frequency of 2%. There is no association between this mutation and any immunodeficiency. Membrane expression of CCR5-893(–) was substantially reduced compared to the wild type, but this defective surface presentation recovered greatly recovered in the presence of 2 mg l-1 phytohemagglutinin (PHA). However, PHA inducement did not affect the total intracellular expression of CCR5-893(–) or wild-type CCR5. Thus we suggest there exist some PHA-induced factor(s) that could mediate the presentation of truncated CCR5. [ABSTRACT FROM AUTHOR]

For the first time, the purification has been achieved of the type II polyhydroxyalkanoate (PHA) synthases PhaC1 and PhaC2 from Pseudomonas aeruginosa applying N-terminal His6-tag fusions and metal chelate affinity chromatography. In vivo His6-tagged PHA synthase activity was confirmed by functional expression of the corresponding genes in Escherichia coli, and PHA synthase activity could also be measured in vitro with the enzymes. The specific enzyme activity of PHA synthases PhaC1 and PhaC2 was 0.039 U mg-1 and 0.035 U mg-1 protein, respectively. Kinetic studies showed a lag phase for both PHA synthases using (R,S)-3-hydroxydecanoyl-CoA as substrate. Specific enzyme activity was increased to 0.055 U mg-1 when the phasin GA24 from Ralstonia eutropha was added to the assay. CoA inhibited PHA synthase activity, and a Ki of 85 μM was determined. A two-enzyme system was established, employing commercially available acyl-CoA synthetase and PHA synthase, which allowed the in vitro de novo PHA granule formation and the in vitro synthesis of poly(3-hydroxydecanoate) exhibiting a weight average molar mass of 9.8 × 104 g mol-1, and which occurred independently of pre-existing PHA granules. [ABSTRACT FROM AUTHOR]