Effects of microplastics (MPs) and tributyltin (TBT) alone and in combination on bile acids and gut microbiota crosstalk in mice.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Antiviral activity of Paulownia tomentosa against enterovirus 71 of hand, foot, and mouth disease.

The bark, leaves, and flowers of Paulownia trees have been used in traditional Chinese medicine to treat infectious and inflammatory diseases. We investigated the antiviral effects of Paulownia tomentosa flowers, an herbal medicine used in some provinces of P. R. China for the treatment of skin rashes and blisters. Dried flowers of P. tomentosa were extracted with methanol and tested for antiviral activity against enterovirus 71 (EV71) and coxsackievirus A16 (CAV16), the predominant etiologic agents of hand, foot, and mouth disease in P. R. China. The extract inhibited EV71 infection, although no effect was detected against CAV16 infection. Bioactivity-guided fractionation was performed to identify apigenin as an active component of the flowers. The EC50 value for apigenin to block EV71 infection was 11.0 µM, with a selectivity index of approximately 9.3. Although it is a common dietary flavonoid, only apigenin, and not similar compounds like naringenin and quercetin, were active against EV71 infection. As an RNA virus, the genome of EV71 has an internal ribosome entry site that interacts with heterogeneous nuclear ribonucleoproteins (hnRNPs) and regulates viral translation. Cross-linking followed by immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that EV71 RNA was associated with hnRNPs A1 and A2. Apigenin treatment disrupted this association, indicating that apigenin suppressed EV71 replication through a novel mechanism by targeting the trans-acting factors. This study therefore validates the effects of Paulownia against EV71 infection. It also yielded mechanistic insights on apigenin as an active compound for the antiviral activity of P. tomentosa against EV71 infection.

Antitumor effects of naturally occurring oligomeric resveratrol derivatives.

This study was designed to evaluate and characterize the molecular basis of antitumor activity of naturally occurring resveratrol (RES; 3,5,4'-trihydroxy-trans-stilbene) derivatives. The compounds were isolated from plants in previous studies and characterized spectroscopically. The antitumor activities of 31 RES derivatives, including dimers, trimers, and tetramers of RES, were evaluated using cell-based assays and validated on a murine model. Several trimeric and a tetrameric stilbenoids induced tumor cell apoptosis or growth arrest of several tumor cell lines with IC50 values (2.8-19.7 µM), significantly lower than that of RES (IC50>70 µM). Using pauciflorol B (PauB) as an example, we showed that the compound induced apoptosis p53 dependently, inducing p53 accumulation and p53-modulated gene expression in cells with wild-type p53, but not in those with nonfunctional p53. Reexpression of p53 in p53-null cells rescued cell death response. In parallel, the MAPK/p38 was activated and critical for PauB-induced killing. Interestingly, activation of p38 in p53 deficient cells was sufficient to drive cells into senescence via the p16-pRb pathway. Finally, PauB dose-dependently inhibited tumor growth on nude mice. Naturally occurring trimeric and tetrameric stilbenoids are potent antitumor agents. Those compounds exert antitumor effect through p53-dependent induction of apoptosis or senescence.

Anaerobic degradation of pesticide wastewater: Improving sludge characteristics and reducing membrane fouling with combined tandem UASB+membrane system with high velocity settlers.

In this pilot study, a combined tandem UASB+membrane reactor (R2) with high velocity settlers was proposed for the treatment of pesticide wastewater at different hydraulic retention times (HRT) and compared with a control reactor (R1). The average COD removal efficiencies of the R2 at HRTs of 96, 72, and 48 h were 83.7 %, 82.8 %, and 74.2 %, which are 14 %, 17 %, and 21 % higher than those of the R1, respectively. Throughout the operation, the biogas production of R2 was 33 %, 19 % and 28 % higher than that of R1 at the same stage, respectively, and the methane yield of R2 (0.19-0.26 L CH4/gCODremoved) was improved by 10-17 % compared to that of R1. Mean α values (VFA/ALK) of 0.13∼0.22 indicated that R2 did not undergo acidification. R2 reduced the extracellular polymers (EPS) content in the attached sludge by 56-62 % compared to R1. It also successfully delayed membrane fouling rate by 19-22 %. The results demonstrate that the R2 has a high treatment capacity, stability, and methane recovery, while also effectively reducing membrane fouling.

New alkaloid from Streptomyces koyangensis residing in Odontotermes formosanus.

A new alkaloid was isolated from the ethyl acetate extract of the culture of a termite-associated Streptomyces koyangensis BY-4. The structure of 1 was elucidated by using MS, NMR, electronic circular dichroism data, and computational approaches. Compound 1 showed weak antimicrobial activities against a panel of test microbes.

Associations Among Self-rated Oral Health, Subjective Oral Conditions, Oral Health Behaviours, and Oral Healthrelated Quality of Life (OHRQoL).

PURPOSE: To evaluate the relationship between self-rated oral health, subjective oral conditions, oral health behaviours, and oral health-related quality of life (OHRQoL) in Chinese college students. MATERIALS AND METHODS: An online cross-sectional survey was conducted, inviting college students from eastern China to participate. A total of 1708 participants were included. A structural equation model was constructed to explain and assess the associations among self-rated oral health, subjective oral conditions, oral health behaviours, and OHRQoL. RESULTS: Self-rated oral health had a direct positive effect on subjective oral conditions and OHRQoL. Oral health behaviours had direct negative impacts on subjective oral conditions and OHRQoL as well as on tooth condition perception and oral health interventions. Subjective oral conditions had a direct positive effect on OHRQoL. There was a positive correlation between oral health behaviours and self-rated oral health. In addition, subjective oral conditions partially mediated both the effect of oral health behaviours on OHRQoL and the effect of self-rated oral health on OHRQoL. CONCLUSION: There were influential associations between self-rated oral health, subjective oral conditions, oral health behaviours, and OHRQoL among college students in eastern China. Making the most of their association can be a guide to radically improving the oral health of college students.

Performance enhancement, membrane fouling mitigation and eco-friendly strategy by electric field coupled membrane bioreactor for treating mariculture wastewater.

An eco-friendly strategy for mariculture wastewater treatment using an electric field attached membrane bioreactor (E-MBR) was evaluated and compared with a conventional membrane bioreactor (C-MBR). The removal efficiencies of total nitrogen (TN) and chemical oxygen demand (COD) increased significantly and the membrane fouling rate reduced by 44.8% in the E-MBR. The underlying mechanisms included the enriched nitrifiers and denitrifiers, the enhanced salinity-resistance, the increased activities and upregulated genes of key enzymes involved in nitrification and denitrification for improving the performance of mariculture wastewater treatment, and the enriched extracellular polymeric substance (EPS)-degrading genera, the downregulated EPS biosynthesis genes, the repressed biofilm-forming bacteria, the enhanced zeta potential absolute value and the generated H2O2 for membrane fouling mitigation by electrical stimulation. Compared with the C-MBR, the energy consumption, carbon emissions, and nitrogen footprint were reduced. These findings provide novel insights into mariculture wastewater treatment using an applied electric field.

Optimizing anaerobic technology by using electrochemistry and membrane module for treating pesticide wastewater: Chemical oxygen demand components and fractions distribution, membrane fouling, effluent toxicity and economic analysis.

Optimization in performance and membrane fouling of an electrochemical anaerobic membrane bioreactor (R1) for treating pesticide wastewater was investigated and compared with a conventional anaerobic membrane bioreactor (R2). The maximum COD removal efficiency of R2 was 80.1%, 80.0%, 67.4%, 61.1% with HRT of 96, 72, 48 and 24 h, which of R1 was enhanced to 84.7%, 84.3%, 82.0% and 66.3%. These results demonstrated that the optimum HRT of R1 was shortened to 48 h, which of R2 required 72 h. R1 reduced the contents of particulate and colloidal COD, and the fraction of COD converted to sludge was 5.0-8.2% lower than that of R2. The fouling rate was 0.99-1.44 kPa/d and reduced by 31.0%-38.5% compared with R2. Detoxification was enhanced by 7.8-47.7% with the assistance of bio-electrochemistry. Ultimately, ensuring similar performance, R1 achieved a 65.6% improvement in environmental benefit, a 26.3% and 38.9% reduction in unit capital and operating costs.

Optimized Neural Network Based on Genetic Algorithm to Construct Hand-Foot-and-Mouth Disease Prediction and Early-Warning Model.

Accompanied by the rapid economic and social development, there is a phenomenon of the crazy spread of many infectious diseases. It has brought the rapid growth of the number of people infected with hand-foot-and-mouth disease (HFMD), and children, especially infants and young children's health is at great risk. So it is very important to predict the number of HFMD infections and realize the regional early-warning of HFMD based on big data. However, in the current field of infectious diseases, the research on the prevalence of HFMD mainly predicts the number of future cases based on the number of historical cases in various places, and the influence of many related factors that affect the prevalence of HFMD is ignored. The current early-warning research of HFMD mainly uses direct case report, which uses statistical methods in time and space to have early-warnings of outbreaks separately. It leads to a high error rate and low confidence in the early-warning results. This paper uses machine learning methods to establish a HFMD epidemic prediction model and explore constructing a variety of early-warning models. By comparison of experimental results, we finally verify that the HFMD prediction algorithm proposed in this paper has higher accuracy. At the same time, the early-warning algorithm based on the comparison of threshold has good results.

Effect of nanoencapsulation using poly (lactide-co-glycolide) (PLGA) on anti-angiogenic activity of bevacizumab for ocular angiogenesis therapy.

Antibody-based therapy is an effective strategy for treating ocular angiogenesis. However, short-acting efficacy and poor treatment compliance usually occurs in clinical practices. Thus, it is required to develop a drug delivery system to improve the bioavailability and decrease the toxicity of anti-angiogenic antibody. Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF). In this study, bevacizumab was encapsulated into poly (lactide-co-glycolide) (PLGA) nanoparticles. PLGA encapsulation could prolong the residency of bevacizumab in the vitreous and aqueous humor and produce long-lasting drug concentrations. Bevacizumab-encapsulated PLGA had no significant cytotoxicity and tissue toxicity effect in vitro and in vivo. In vitro studies showed that bevacizumab-encapsulated PLGA was more effective than bevacizumab in inhibiting VEGF-mediated endothelial cell proliferation, migration and tube formation. In vivo studies showed that bevacizumab-encapsulated PLGA enhanced the anti-angiogenic efficiency of bevacizumab for treating corneal neovascularization and retinal neovascularization. Thus, bevacizumab-encapsulated PLGA could increase the bioavailability and decrease the toxicity of bevacizumab during ocular angiogenesis therapy.

Differential diagnosis of gastric cancer and gastritis: the role of contrast-enhanced ultrasound (CEUS).

OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of gastric cancer and gastritis, with histological results as reference standard. METHODS: From September 2011 to August 2014, 82 patients (50 males and 32 females; mean age ± SD, 59.5 ± 15.0 years; range 19-91 years) with gastric cancer or gastritis were included in this Ethics Committee-approved prospective study. Conventional ultrasonography (US) and CEUS were applied to distinguish the two lesions, and both qualitative and quantitative features were evaluated. RESULTS: Of the 82 histopathologic-proven lesions, 58 were cancer and 24 were gastritis. For US, the gastric wall stratification was not preserved in about one-third of cancer (21/58, 36.2%) compared with gastritis (0/24, 0%) (p < 0.001). Blurred, angular, or spiculated serosa margin and increased echogenicity in perigastric fat appeared only in cancer (10/58, 17.2%), and all of them proved to be pathologic T3 or T4 stage. On CEUS, gastric cancer usually manifested as diffused enhancement without comb-teeth-like vessels (parallel curvilinear structures representing arterial branching within the gastric wall) (56/58, 96.6%), while these vessels presented in most gastritis (19/24, 79.2%, p < 0.001). For quantitative analysis, the malignant lesions showed later and lower enhancement (p < 0.001), and they also had slower speed to reach the peak intensity (p < 0.001). On CEUS, the absence of comb-teeth-like vessel is most reliable for diagnosing malignancy, and the sensitivity, specificity, and accuracy were 96.5%, 79.2%, and 91.5%, respectively. CONCLUSIONS: Our results demonstrated the usefulness and accuracy of US and CEUS in differential diagnosis of gastric cancer and gastritis. CEUS has the potential to make the diagnosis more accurate.

Temperature-controlled release of diols from N-isopropylacrylamide-co-acrylamidophenylboronic acid microgels.

N-Isopropylacrylamide-co-acrylamidophenylboronic acid (NIPAM-co-PBA) microgels were prepared by free radical polymerization in water. The release of glucose and Alizarin Red S (ARS) from the microgels as a function of temperature has been investigated by using laser light scattering (LLS) and ultrasensitive differential scanning calorimetry (US-DSC). Such microgels can bind glucose and ARS via boronic acids at a lower temperature. As the temperature increases, the microgels shrink, and the diols are released. The release could be controlled by temperature. The effect of the structure of the microgels on the release is also discussed.

Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease.

ETHNOPHARMACOLOGICAL RELEVANCE: The radices of Glycyrrhiza uralensis Fisch. and herbal preparations containing Glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in China. Glycyrrhizic acid (GA) is considered the principal component in Glycyrrhiza spp. with a wide spectrum of antiviral activity. AIM: The present study attempt to validate the medicinal use of Glycyrrhiza uralensis for hand, foot and mouth disease (HFMD) and further to verify whether GA is an active antiviral component in the water extract of Glycyrrhiza uralensis. MATERIALS AND METHODS: Radices of Glycyrrhiza uralensis Fisch. were extracted with hot water. The chemical contents of the extract were profiled with HPLC analysis. The antiviral activity of the extract and the major components was evaluated against infection of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) on Vero cells. The cytopathic effect caused by the infection was measured with MTT assay. Infectious virion production was determined using secondary infection assays and viral protein expression by immunoblotting analysis. RESULTS: The extract at 1000 µg/ml suppressed EV71 replication by 1.0 log and CVA16 by 1.5 logs. The antiviral activity was associated with the content of GA in the extract since selective depletion of GA from the extract by acid precipitation resulted in loss of antiviral activity. In contrast, the acid precipitant retained antiviral activity. The precipitant at a concentration of 200 µg/ml inhibited EV71 and CVA16 replication by 1.7 and 2.2 logs, respectively. Furthermore, GA dose-dependently blocked viral replication of EV71 and CVA16. At 3 mM, GA reduced infectious CVA16 and EV71 production by 3.5 and 2.2 logs, respectively. At 5mM, CVA16 production was reduced by 6.0 logs and EV71 by 4.0 logs. Both EV71 and CVA16 are members of Enterovirus genus, time-of-drug addition studies however showed that GA directly inactivated CVA16, while GA anti-EV71 effect was associated with an event(s) post virus cell entry. CONCLUSIONS: This study validated the medicinal usefulness of radices Glycyrrhiza uralensis against the etiological agents of HFMD. In addition to the identification of GA as the antiviral component of Glycyrrhiza uralensis against EV71 and CVA16 infection, this study also reveals that GA inhibits EV71 and CVA16 with distinct mechanisms.

New acrylamide and oxazolidin derivatives from a termite-associated Streptomyces sp.

Two new compounds, named 2-formylpyrrole-4-acrylamide (1) and dihydrostreptazolin (2) were isolated from the fermentation broth of BY-4, an actinomycetes residing in the gut of Odontotermes formosanus. The structures of 1 and 2 were elucidated by extensive spectral analysis (1H, 13C, 2D NMR, and HR-ESIMS). The isolated compounds were assayed for cytotoxic and antimicrobial activities.

[Electrochemically reductive dechlorination of chloroform by palladium/polymeric pyrrole film/foam-nickel composite electrode in acidic system].

Palladium/polymeric pyrrole film/foam-nickel (Pd/PPy/foam-Ni) composite electrode were prepared by the electrodeposition method with the electrodepositing current density of 5 mA x cm(-2) and the electrodepositing time of 40 min. Electrochemical reductive dechlorination of chloroform in acidic system was investigated using the Pd/PPy/foam-Ni electrode at ambient temperature. The electrochemical deposition behaviors of Pd/PPy/foam-Ni electrode were studied by means of cyclic voltammetry (CV). Cyclic voltammetry results reveal that the large hydrogen adsorption peak current of -100 mA on Pd/PPy/foam-Ni electrode was obtained at about -500 mV (vs Hg/Hg2 SO4). SEM micrographs show that the addition of polymeric pyrrole changed the distributing configuration of Pd microparticles on the electrode and Pd/PPy/foam-Ni electrode possessed a good spatial extension. Chloroform dechlorination experimentes were conducted in acid system. Dechlorination experimental results indicate that, with the integrated analysis of removal efficiency and current efficiency, with the high current efficiency of 44.17%, the removal efficiency of chloroform on Pd/PPy/foam-Ni electrode was 49.23%, under the optimum conditions of the dechlorination current density of 0.05 mA x cm(-2) and the dechlorination time of 180 min. In acid aqueous solution, with low initial concentration of chloroform, the results of dechlorination experiment were preferable.

{[Cu2(bpdado)2(H2O)2].H2O}n: a 1D nanotubular coordination polymer with wall made of edge-sharing hexagons, where bpdado = 2,2'-bipyridine-3,3'-dicarboxylate-1,1'-dioxide.

Utilizing 2,2'-bipyridine-3,3'-dicarboxylate-1,1'-dioxide and Cu2+ ions produces an antiferromagnetic, 1D nanotubular coordination polymer with its wall composed of edge-sharing hexagons, topologically similar to carbon nanotube.