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Summary: Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy‐eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single‐centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin‐like effect was confirmed by a protamine neutralization test and anti‐Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk. [ABSTRACT FROM AUTHOR]

Numerous epidemiological findings have shown that di-(2-ethylhexyl)-phthalate (DEHP), one of industrial plasticizers with endocrine-disrupting properties, positively contributes to high incidence of obesity. However, potential pathogenesis of dietary DEHP exposure-induced obesity remains largely unknown. Chronic DEHP exposure at different doses (0.05 and 5 mg/kg body weight) to mice had been continuously lasted for 14 weeks through the diet. A combination of targeted quantitative metabolomics (LC/GC-MS) with global 1H NMR-based metabolic profiling to explore the effects of dietary DEHP exposure with different doses on host lipid metabolism of mice. Metagenomics (16S rRNA gene sequencing) was also employed to examine the alterations of gut microbiota composition in the cecal contents of mice after dietary DEHP exposure. Dietary exposure to DEHP at both doses induced weight gain and hepatic lipogenesis of mice by promoting the uptake of fatty acids and disrupting phospholipids and choline metabolism. Dietary DEHP exposure altered the gut microbiota community with disruption of intestinal morphology and reduction of Firmicutes to Bacteroidetes ratio in the cecal contents of mice. Furthermore, DEHP exposure activated gut microbiota fermentation process producing excess short chain fatty acids of mice. These findings provide systematic evidence that long-term chronic DEHP exposure induces obesity through disruption of host lipid metabolism and gut microbiota in mice, which not only confirm the epidemiological results, but also expand our understanding of metabolic diseases caused by environmental pollutants exposure. [Display omitted] • Dietary DEHP induced body weight gain, lipid and triglyceride accumulation of mice. • Dietary DEHP induced abnormal metabolism of phospholipids and choline of mice. • DEHP disrupted microbial morphology and composition with promotion of fermentation. [ABSTRACT FROM AUTHOR]

• TCC exposure promoted adipocyte differentiation in 3T3L1 preadipocytes. • TCC exposure triggered endoplasmic reticulum (ER) stress in both 3T3L1 and L02 cells. • TCC exposure induced toxic lipid accumulation in both cells. • TCC exposure induced opposite effects on ceramides metabolism in 3T3L1 and L02 cells. Triclocarban (TCC), a widely used antibacterial agent, has aroused considerable public concern due to its potential toxicity. In the current study, we applied targeted metabolite profiling (LC/GC−MS) and untargeted 1H NMR-based metabolomics in combination with biological assays to unveil TCC exposure-induced cellular metabolic responses in murine preadipocyte and human normal hepatocytes. We found that TCC promoted adipocyte differentiation in 3T3L1 preadipocytes, manifested by marked triglyceride (TG) and fatty acids accumulation, which were consistent with significant up-regulation of mRNA levels in the key adipogenic markers Fasn , Srebp1 and Ap2. In human hepatocytes (L02), TCC exposure dose-dependently interfered with the cellular redox state with down-regulated levels of antioxidant reduced-GSH and XBP1 and further induced the accumulation of TG, ceramides and saturated fatty acid (16:0). We also found that TCC exposure triggered unfold protein response (UPR) and endoplasmic reticulum (ER) stress in both cells through activation of ATF4 and ATF6, resulting in toxic lipid accumulation. These findings about lipid metabolism and metabolic responses to TCC exposure in both preadipocytes and hepatocytes provide novel perspectives for revealing the mechanisms of TCC toxicity. [ABSTRACT FROM AUTHOR]

In this paper, mesoporous monometallic Cu catalysts reinforced by the Al3+ dopants with different chemical features were successfully synthesized by controlling the preparation process. The N2‐Adsorption/Desorption, XRD, H2‐TPR, SEM, TEM, H2‐TPD and XPS were conducted to explore the structure evolution of the as‐synthesized samples focusing on the interface effect between Cu nano‐particles (NPs) and Al3+ dopants. It is found that the precipitants used for preparing precursors show drastically effect on the Al3+ chemical form and Cu/Al bonding manners of the as‐synthesized CuAl catalysts, further determining the resultant physicochemical properties and catalytic behavior in dimethyl oxalate (DMO) hydrogenation. In gas‐phase DMO hydrogenation, 98.0 % ethylene glycol (EG) and 90.0 % ethanol (EtOH) yield from DMO selective hydrogenation can be achieved over the CuAl catalyst by regulating the reaction temperature. The correlation between the catalytic behavior and physicochemical features shows that the surface Cu+ sites generated in the Cu/(hydr)oxide interface should be essential for DMO selective hydrogenation in presence of the adequate Cu0 sites. Additionally, the Cu−O−Al patterns in the Cu/Al interface intend to promote more electron transferred from the Al3+ dopants to Cu species through the O bridging, facilitating the CuAl(O) stronger Cu/Al interaction than that of the CuAl(C) catalyst in form of Cu−Al−OH mode. Thus, the Cu NPs growth of the CuAl(O) catalyst was effectively retarded, favoring enhanced catalytic stability. [ABSTRACT FROM AUTHOR]

Al2O3 doped mesoporous monometallic Cu catalysts were successfully synthesized though the self-assembly Cu species derived from the oxalate precursor undergoing thermal decomposing. The evolutions of microstructures, physicochemical and surface properties of the CuAl catalysts have been systematically characterized focusing on the effect of the calcination temperature during catalyst preparation. It is found that the textural and surface properties of the CuAl catalysts were profoundly affected by the calcination temperature, further determining the resultant catalytic behavior in dimethyl oxalate (DMO) hydrogenation. Particularly, the CuAl-500 possessing the maximum surface Cu+ sites and proper surface acid features exhibits 100.0% DMO conversion and 98.0% ethylene glycol (EG) selectivity in presence of the adequate active Cu0 sites, which is superior to that of the other catalysts under the identical reaction conditions. And no activity loss occurred for more than 200 h demonstrated of the outstanding stability of the CuAl-500 catalyst. Moreover, the synergistic effect between surface Cu+ and Cu0 sites should be responsible for DMO selective hydrogenation. Additionally, the strengthened chemical interaction between Cu and Al species endows the catalysts outstanding stability by suppressing the dispersive Cu NPs agglomeration during DMO hydrogenation. [ABSTRACT FROM AUTHOR]

Hydrophilic metabolites are essential for all biological systems with multiple functions and their quantitative analysis forms an important part of metabolomics. However, poor retention of these metabolites on reversed-phase (RP) chromatographic column hinders their effective analysis with RPLC-MS methods. Herein, we developed a method for detecting hydrophilic metabolites using the ion-pair reversed-phase liquid-chromatography coupled with mass spectrometry (IPRP-LC-MS/MS) in scheduled multiple-reaction-monitoring (sMRM) mode. We first developed a hexylamine-based IPRP-UHPLC-QTOFMS method and experimentally measured retention time (t R) for 183 hydrophilic metabolites. We found that t R s of these metabolites were dominated by their electrostatic potential depending upon the numbers and types of their ionizable groups. We then systematically investigated the quantitative structure-retention relationship (QSRR) and constructed QSRR models using the measured t R. Subsequently, we developed a retention time predictive model using the random-forest regression algorithm (r 2 = 0.93, q 2 = 0.70, MAE = 1.28 min) for predicting metabolite retention time, which was applied in IPRP-UHPLC-MS/MS method in sMRM mode for quantitative metabolomic analysis. Our method can simultaneously quantify more than 260 metabolites. Moreover, we found that this method was applicable for multiple major biological matrices including biofluids and tissues. This approach offers an efficient method for large-scale quantitative hydrophilic metabolomic profiling even when metabolite standards are unavailable. [Display omitted] • Retention times of 183 metabolites from hexylamine-based IP-RPLC-QTOF MS. • QSRR models for predicting metabolite retention times in metabolomic analysis using the sMRM-based IPRP-LC-MS/MS. • Quantitative metabolomic profiling method covering more than 260 metabolites in multiple biological matrices. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the diagnostic efficiency of human neutrophil lipocalin (HNL) in bacterial infections in children. This study included 49 pediatric patients with bacterial infections, 37 patients with viral infections, 30 patients with autoimmune diseases (AID) and 41 healthy controls (HCs). HNL, procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts were detected in the initial diagnosis and the following days. In the patients with bacterial infections, the levels of HNL, PCT, CRP, WBC and neutrophils were significantly increased than that of disease controls and HCs. The dynamic of these markers was monitored during antibiotic treatment. The level of HNL was decreased rapidly in patients with effective treatment, but maintained at high levels in deteriorated patients according to the clinical progression. HNL detection is an effective biomarker to identify bacterial infections from viral infections and other AIDs, and has potential value to evaluate the effect of antibiotic treatment in pediatric patients. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, a dual chelating sol–gel method was used to synthesize BaTiO3 nanoparticles by using acetylacetone and citric acid as chelating agents. The samples calcined at different temperatures were analyzed by thermogravimetric and differential thermal analysis (TG-DTA), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS), scanning electron microscope (SEM) and UV–vis diffuse reflectance spectra (UV–vis). The results indicated that cubic phase BaTiO3 nanoparticles about 19.6nm can be obtained at 600°C and changed into tetragonal phase at 900°C about 97.1nm. All the BaTiO3 nanoparticles showed effective photocatalytic activities on the removal of humic acid (HA) under UV light irradiation. A comparison of single (acetylacetone or citric acid) and dual chelating (acetylacetone and citric acid) synthetic processes was also studied and the results demonstrated that the dual chelating agents indeed reduced phase transformation temperature from cubic to tetragonal BaTiO3. [Copyright &y& Elsevier]

Recent studies report that the gut microbiome can enhance systemic and antitumor immunity by modulating responses to antibody immunotherapy in melanoma patients. In this study, we found that icariside I, a novel anti-cancer agent isolated from Epimedium , significantly inhibited B16F10 melanoma growth in vivo through regulation of gut microbiota and host immunity. Oral administration of icariside I improved the microbiota community structure with marked restoration of Lactobacillus spp. and Bifidobacterium spp. abundance in the cecal contents of tumor-bearing mice. We also found that icariside I improves the levels of microbiota-derived metabolites such as short-chain fatty acids (SCFAs) and indole derivatives, consequently promoting repair of the intestinal barrier and reducing systemic inflammation of tumor-bearing mice. Icariside I exhibited strong immunological anti-tumor activity, directly manifested by up-regulation of multiple lymphocyte subsets including CD4+ and CD8+ T cells or NK and NKT cells in peripheral blood of tumor-bearing mice. Collectively, these results suggest that icariside I, via its microbiome remodeling and host immune regulation properties, may be developed as an anticancer drug. • Icariside I inhibits melanoma growth in B16F10-xenograft model. • Icariside I improves intestinal gut microbiota and its metabolites. • Icariside I improves host immunity for inhibition of tumor growth. • Enhanced host immunity positively correlated with gut microbiota and its metabolites. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a well-known endocrine disruptor, was reported to promote migration and invasion of lung cancer cells, but findings in human study is absent. A case-control study in Chinese population was conducted to evaluate the association between BPA exposure and non-small cell lung cancer (NSCLC), and explore the interaction between BPA exposure and estrogen-related genetic polymorphism on NSCLC. BPA concentrations were measured in urine samples using an UHPLC-MS method and rs2046210 in estrogen receptor α (ESR1) gene was genotyped by TaqMan genotyping system. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association analyses. As a result, 615 NSCLC cases and 615 healthy controls were enrolled from Wuhan, central China. The mean age was 58.0 (SD: 7.9) years old for controls and 59.2 (SD: 8.8) years old for cancer cases. The creatinine-adjusted BPA levels were significantly higher in NSCLC cases than that in healthy controls (median: 0.97 vs 0.73 μg/L, P < 0.001). Exposure to high levels of BPA was significantly associated with NSCLC (adjusted OR = 1.91, 95%CI: 1.39–2.62, P < 0.001 for the highest quartile). We also observed a shallow concave dose-response relationship about the overall association between BPA and NSCLC. Moreover, interaction analyses showed that BPA exposure interacted multiplicatively with rs2046210, with a marginal P value (P = 0.049), to contribute to NSCLC. In conclusion, exposure to high levels BPA may be associated with NSCLC and the relationship may be modified by genetic polymorphism in ESR1. • The bisphenol A (BPA) level was higher in non-small cell lung cancer (NSCLC) cases than controls. • BPA was significantly associated with NSCLC, particularly in non-smokers. • BPA exposure interacted with ESR1 rs2046210 to contribute to NSCLC. [ABSTRACT FROM AUTHOR]

• TERT -rs33963617 and CLPTM1L -rs77518573 conferred reduced risk for NSCLC. • The associations of these 2 variants and NSCLC may be specific in Chinese population. • An obvious cumulative effect was observed between rs33963617 and rs77518573. Genome-wide association studies (GWAS) have identified 5p15.33 as a susceptible locus for lung cancer. However, for non-small cell lung cancer (NSCLC), low-frequency risk variants in this region have not been systematically studied. We intended to explore the associations between low-frequency variants on 5p15.33 and NSCLC using a next-generation sequencing based approach in this study. We have acquisited the variation spectrum of 400 NSCLC patients on 5p15.33 by sequencing the targeted region before. Candidate variants were primarily selected by restricting the minor allele frequency (MAF 1–5%) and then by comparing their frequency in 400 NSCLC patients with 1008 East Asians from The genome Aggregation Database (gnomAD). The associations between candidate variants and NSCLC were discovered and replicated in two case-control sets: discovery stage with 960 cases and 916 controls, and replication stage with 1596 cases and 1614 controls in total. Five low-frequency variants were selected as our candidates and subsequent association analyses showed that 2 polymorphisms were significantly associated with risk of NSCLC, including rs33963617 (OR = 0.63, 95% CI: 0.53–0.76, P = 3.80 × 10−7) in TERT and rs77518573 (OR = 0.73, 95% CI: 0.63–0.84, P = 2.00 × 10−5) in upstream of CLPTM1L. When stratified by histologic subtype, a significant association was only investigated in adenocarcinoma for rs77518573. We also observed an obvious cumulative effect of the two significant variants. We newly identified two NSCLC related variants on chromosome 5p15.33. Both TERT -rs33963617 and CLPTM1L -rs77518573 conferred reduced risk for NSCLC in Chinese Han population. [ABSTRACT FROM AUTHOR]