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Relationship of genetic polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and interleukin-18 (IL-18) with susceptibility to viral hepatitis was already investigated by many association studies. The aim of this study was to more comprehensively analyse associations between genetic polymorphisms in CTLA-4/IL-18 and viral hepatitis by combing the results of all relevant association studies. We searched Pubmed, Embase, Web of Science and CNKI for eligible studies. We used Review Manager to combine the results of eligible studies. Thirty-seven studies were finally included in this meta-analysis. Combined results demonstrated that CTLA-4 rs231775 (recessive comparison: OR 1.31, 95% CI 1.11–1.55), IL-18 rs1946518 (dominant comparison: OR 0.82, 95% CI 0.75–0.90; recessive comparison: OR 1.29, 95% CI 1.11–1.50; allele comparison: OR 0.76, 95% CI 0.68–0.86) and IL-18 rs187238 (dominant comparison: OR 1.25, 95% CI 1.03–1.52; allele comparison: OR 1.20, 95% CI 1.05–1.37) polymorphisms were all significantly associated with viral hepatitis in the general population. Further subgroup analyses revealed that CTLA-4 rs231775, IL-18 rs1946518 and IL-18 rs187238 polymorphisms were significantly associated with susceptibility to hepatitis B virus (HBV), especially among East Asians. Moreover, CTLA-4 rs5742909, IL-18 rs1946518 and IL-18 rs187238 polymorphisms were also significantly associated with susceptibility to hepatitis C virus (HCV), especially among South Asians. So to conclude, this meta-analysis demonstrated that CTLA-4 rs231775, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to HBV in East Asians, while CTLA-4 rs5742909, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to HCV in South Asians.
Previous studies have shown that the Dietary Approaches to Stop Hypertension (DASH) diet might contribute to managing risk factors of non-alcoholic fatty liver disease (NAFLD), but evidence is limited. We examined the association of DASH diet score (DASH-DS) with NAFLD, as well as the intermediary effects of serum retinol-binding protein-4 (RBP4), serum high-sensitivity C-reactive protein (hs-CRP), serum TAG, homeostasis model assessment of insulin resistance (HOMA-IR) and BMI.
We performed a cross-sectional analysis of a population-based cohort study. Dietary data and lifestyle factors were assessed by face-to-face interviews and the DASH-DS was then calculated. We assessed serum RBP4, hs-CRP and TAG and calculated HOMA-IR. The presence and degree of NAFLD were determined by abdominal sonography.
Guangzhou Nutrition and Health Study participants, aged 40–75 years at baseline (n 3051).
After adjusting for potential covariates, we found an inverse association between DASH-DS and the presence of NAFLD (Ptrend = 0·009). The OR (95 % CI) of NAFLD for quintiles 2–5 were 0·78 (0·62, 0·98), 0·74 (0·59, 0·94), 0·69 (0·55, 0·86) and 0·77 (0·61, 0·97), respectively. Path analyses indicated that a higher DASH-DS was associated with lower serum RBP4, hs-CRP, TAG, HOMA-IR and BMI, which were positively associated with the degree of NAFLD.
Adherence to the DASH diet was independently associated with a marked lower prevalence of NAFLD in Chinese adults, especially in women and those without abdominal obesity, and might be mediated by reducing RBP4, hs-CRP, TAG, HOMA-IR and BMI.
Echinococcus granulosus sensu stricto (s.s.), Echinococcus multilocularis and Echinococcus canadensis are the common causes of human echinococcosis in China. An accurate species identification tool for human echinococcosis is needed as the treatments and prognosis are different among species. The present work demonstrates a method for the simultaneous detection of these three Echinococcus species based on multiplex polymerase chain reaction (mPCR). Specific primers of this mPCR were designed based on the mitochondrial genes and determined by extensive tests. The method can successfully detect either separated or mixed target species, and generate expected amplicons of distinct size for each species. Sensitivity of the method was tested by serially diluted DNA, showing a detection threshold as less as 0.32 pg for both E. granulosus s.s. and E. canadensis, and 1.6 pg for E. multilocularis. Specificity assessed against 18 other parasites was found to be 100% except weakly cross-react with E. shiquicus. The assay was additionally applied to 69 echinococcosis patients and 38 healthy persons, confirming the high reliability of the method. Thus, the mPCR described here has high application potential for clinical identification purposes, and can further provide a useful tool for evaluation of serology and imaging method.
Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
Limited information is available on the prevalence and effect of hypertriglyceridaemic–waist (HTGW) phenotype on the risk of type 2 diabetes mellitus (T2DM) in rural populations.
In the present cross-sectional study, we investigated the prevalence of the HTGW phenotype and T2DM and the strength of their association among rural adults in China.
HTGW was defined as TAG >1·7 mmol/l and waist circumference (WC) ≥90 cm for males and ≥80 cm for females. Logistic regression analysis yielded adjusted odds ratios (aOR) relating risk of T2DM with HTGW.
Adults (n 12 345) aged 22·83–92·58 years were recruited from July to August of 2013 and July to August of 2014 from a rural area of Henan Province in China.
The prevalence of HTGW and T2DM was 23·71 % (males: 15·35 %; females: 28·88 %) and 11·79 % (males: 11·15 %; females: 12·18 %), respectively. After adjustment for sex, age, smoking, alcohol drinking, blood pressure, physical activity and diabetic family history, the risk of T2DM (aOR; 95 % CI) was increased with HTGW (v. normal TAG and WC: 3·23; CI 2·53, 4·13; males: 3·37; 2·30, 4·92; females: 3·41; 2·39, 4·85). The risk of T2DM with BMI≥28·0 kg/m2, simple enlarged WC and simple disorders of lipid metabolism showed an increasing tendency (aOR=1·31, 1·75 and 2·32).
The prevalence of HTGW and T2DM has reached an alarming level among rural Chinese people, and HTGW is a significant risk factor for T2DM.
To eliminate the toxic effect of chemotherapy drug of lobaplatin (LBP) on body tissue in liver cancer therapy, this work prepared a nanodrug carrier based on polyethylene glycol-modified carbon nanotubes (PEG–CNTs) and then constructed a targeted drug delivery system (LBP–PEG–CNTs) by loading LBP on PEG–CNTs. Fluorescein isothiocyanate (FITC) was used to label PEG–CNTs to observe the cellular uptake of PEG–CNTs. In addition, the inhibitions of LBP–PEG–CNTs on HepG2 cells were investigated. The results show that the FITC-labeled PEG–CNTs have good cell penetrability; meanwhile, LBP–PEG–CNTs have good stability, pH-controlled release property, and high inhibition rate on HepG2 cells. To be specific, 80% of LBP is released under physiological conditions of liver cancer cells at pH 5.0, and LBP–PEG–CNTs show a high inhibition rate of 77.86% on HepG2 cells, demonstrating that they have targeted, pH-controlled release and inhibition properties on HepG2 cells.
Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS).
Apathy was assessed through the Apathy Evaluation Scale (AES). 1H MRS was performed to measure neurochemical metabolite levels in the anterior cingulate region and right orbitofrontal region. Associations between neurochemical metabolites and the total score and subscores of each domain of the AES were analyzed.
Altogether, 36 patients completed the study. Patients with lower N-acetylaspartate/creatine ratios (NAA/Cr) in the anterior cingulate region demonstrated higher total apathy scores (β = −0.56, p = 0.003) with adjustments for age, gender, educational level, dementia severity, and depression severity. In a further analysis, a lower NAA/Cr in the anterior cingulate region was associated with all subdomains of apathy, including cognition (β = −0.43, p = 0.028), behavior (β = −0.55, p = 0.002), and emotion (β = −0.50, p = 0.005). No statistically significant associations were discovered in the right orbitofrontal region.
Our results suggest that apathy, in each of its cognitive, behavioral, or emotional subdomains is associated with brain neurochemical alterations in the anterior cingulate region. Abnormal neuronal integrity over the anterior cingulate cortex may exhibit a central role in causing all aspects of apathy in patients with AD.
Isolation of multidrug-resistant gram-negative bacteria (MDR-GNB) from patients in the community has been increasingly observed. A prediction model for MDR-GNB colonization and infection risk stratification on hospital admission is needed to improve patient care.
A 2-stage, prospective study was performed with 995 and 998 emergency department patients enrolled, respectively. MDR-GNB colonization was defined as isolates resistant to 3 or more classes of antibiotics, identified in either the surveillance or early (≤48 hours) clinical cultures.
A score-assigned MDR-GNB colonization prediction model was developed and validated using clinical and microbiological data from 995 patients enrolled in the first stage of the study; 122 of these patients (12.3%) were MDR-GNB colonized. We identified 5 independent predictors: age>70 years (odds ratio [OR], 1.84 [95% confidence interval (CI), 1.06–3.17]; 1 point), assigned point value in the model), residence in a long-term-care facility (OR, 3.64 [95% CI, 1.57–8.43); 3 points), history of cerebrovascular accidents (OR, 2.23 [95% CI, 1.24–4.01]; 2 points), hospitalization within 1 month (OR, 2.63 [95% CI, 1.39–4.96]; 2 points), and recent antibiotic exposure (OR, 2.18 [95% CI, 1.16–4.11]; 2 points). The model displayed good discrimination in the derivation and validation sets (area under ROC curve, 0.75 and 0.80, respectively) with the best cutoffs of<4 and ≥4 points for low- and high-risk MDR-GNB colonization, respectively. When applied to 998 patients in the second stage of the study, the model successfully stratified the risk of MDR-GNB infection during hospitalization between low- and high-risk groups (probability, 0.02 vs 0.12, respectively; log-rank test, P<.001).
A model was developed to optimize both the decision to initiate antimicrobial therapy and the infection control interventions to mitigate threats from MDR-GNB.
Nine possible native point defects in MgCaSi have been studied by employing density functional theory based ab initio calculations. The complex chemical potential limits are first determined using a two-dimension (∆μMg, ∆μCa) diagram, then the defect formation energies as a function of the atomic chemical potential are gained. The energetic results show that under Mg-rich conditions, the most favorable defect is MgCa rather than MgSi, while CaMg is predominant compared to CaSi under Ca-rich conditions. The bonding energy is first introduced to uncover the intrinsic feature of defect formation energy. The local geometric distortion around CaMg, MgSi, and CaSi antisite defects gradually increases due to the smaller atomic radii from Ca to Mg and Si, showing the important role of the geometrical mismatch. The density of states indicates that the higher stability of CaMg and MgCa originates from the smaller deviation of the Fermi level from the pseudo-gap.
Based on the relaxed factorization techniques studied recently and the idea of the simple-like preconditioner, a modified relaxed positive-semidefinite and skew-Hermitian splitting (MRPSS) preconditioner is proposed for generalized saddle point problems. Some properties, including the eigenvalue distribution, the eigenvector distribution and the minimal polynomial of the preconditioned matrix are studied. Numerical examples arising from the mixed finite element discretization of the Oseen equation are illustrated to show the efficiency of the new preconditioner.
In this paper, an ultra-wideband (UWB) filter with a notch band using T-shaped step impedance resonator loaded with cross-shaped open stubs has been presented. The notch band is formed by utilizing intrinsic zero. The characteristics of the new quad-mode resonator have been analyzed using odd-even mode analysis method. It can be shown that it is the intrinsic zero that generates the notch band. In addition, wide tunable notch band form 5–9.3 GHz can be achieved. A UWB filter with a notch band centered at 6.25 GHz using the proposed quad-mode resonator has been designed, fabricated, and tested. Experiment results show that the attenuation in notch frequency is >22 dB while the return loss of the simulation and measurement results are 22 dB/20 dB and 14.5 dB/11.2 dB in the lower and upper passband, respectively, which illustrate that the simulation and measurement results are in agreement.
The metamorphic responses of mussel (Mytilus coruscus) larvae to pharmacological agents affecting G proteins and the adenylate cyclase/cyclic AMP (AC/cAMP) pathway were examined in the laboratory. The G protein activators guanosine 5′-[β,γ-imido]triphosphate trisodium salt hydrate and guanosine 5′-[γ-thio]triphosphate tetralithium salt only induced larval metamorphosis in continuous exposure assays, and the G protein inhibitor guanosine 5′-[β-thio]diphosphate trilithium salt did not exhibit inducing activity. The non-specific phosphodiesterase inhibitor theophylline and the cAMP-specific phosphodiesterase IV inhibitor 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one exhibited inducing activity, while the non-specific phosphodiesterase inhibitor 3-Isobutyl-1-methylxanthine only showed inducing activity at 10−4 M in continuous exposure assays. The cyclic nucleotide analogue N6,2′-O-Dibutyryladenosine 3′,5′-cyclic monophosphate sodium salt did not exhibit significant inducing activity. Both the adenylate cyclase activator forskolin and the adenylate cyclase inhibitor nitroimidazole exhibited inducing activity at 10−4 to 10−3 M concentrations in continuous exposure assays. Among these tested agents, the adenylate cyclase inhibitor (±)-miconazole nitrate salt showed the most promising inducing effect. The present results indicate that G protein-coupled receptors and signal transduction by AC/cAMP pathway could mediate metamorphosis of larvae in this species.
Astronomy cloud computing environment is a cyber-Infrastructure for Astronomy Research initiated by Chinese Virtual Observatory (China-VO) under funding support from NDRC (National Development and Reform commission) and CAS (Chinese Academy of Sciences). Based on virtualization technology, astronomy cloud computing environment was designed and implemented by China-VO team. It consists of five distributed nodes across the mainland of China. Astronomer can get compuitng and storage resource in this cloud computing environment. Through this environments, astronomer can easily search and analyze astronomical data collected by different telescopes and data centers , and avoid the large scale dataset transportation.
Epidemiological data show that osteoarthritis (OA) is significantly associated with lower birth weight, and that OA may be a type of fetal-originated adult disease. The present study aimed to investigate the prenatal food-restriction (PFR) effect on the quality of articular cartilage in female offspring to explore the underlying mechanisms of fetal-originated OA. Maternal rats were fed a restricted diet from gestational day (GD) 11 to 20 to induce intra-uterine growth retardation. Female fetuses and female adult offspring fed a post-weaning high-fat diet were killed at GD20 and postnatal week 24, respectively. Serum and knee cartilage samples from fetuses and adult female offspring were collected and examined for cholesterol metabolism and histology. Fetal serum corticosterone and insulin-like growth factor-1 (IGF-1) in the PFR group were lower than those of the control, but the serum cholesterol level was not changed. The lower expression of IGF-1 in the PFR group lasted into adulthood. The expression of extracellular matrix (ECM) genes, including type II collagen, aggrecan and cholesterol efflux genes including liver X receptor, were significantly induced, but the ATP-binding-cassette transporter A1 was unchanged. PFR could induce a reduction in ECM synthesis and impaired cholesterol efflux in female offspring, and eventually led to poor quality of articular cartilage and OA.
The Honggong pluton is the largest ferroan alkalic (A-type) granite intrusion emplaced along the Jiangshan–Shaoxing fault zone in southwestern Zhejiang Province, and has important implications for understanding the Late Mesozoic tectonic evolution of SE China. U–Pb ages of 138.7 ± 0.8, 134.2 ± 1.1, 128.5 ± 1.5 and 126.1 ± 0.9 Ma were obtained from zircon by laser ablation–inductively coupled plasma–mass spectrometry, indicating that the Honggong pluton formed in the Early Cretaceous. The Honggong pluton has a clear ferroan alkalic (A-type) granite geochemical signature with, for example, high total alkali contents and FeOt/(FeOt + MgO) values. The Sr–Nd–Hf isotopic compositions suggest that there was juvenile material in the magma source. Geochemical evidence indicates that the pluton was derived through extensive fractionation of melts that contained both asthenospheric mantle and Mesoproterozoic crustal components. These rare granites in southern China were emplaced during five episodes at 235–225, 190, 165–155, 100–90 and 140–120 Ma. The age of the Honggong pluton suggests that localized extension in southwestern Zhejiang Province began as early as ~138 Ma and continued to 126 Ma. This Early Cretaceous extensional event was triggered by localized rollback of the subducting Pacific Plate.