Explore the vast range of titles available.

Local pathogens can accumulate as asymptomatic endophytes, making it difficult to detect the impacts of invasive species as propagators of disease in the invaded range. We used the invasive plant Ageratina adenophora to assess such accumulation. We intensively collected foliar fungal endophytes and leaf spot pathogens of A. adenophora and co-occurring neighbours and performed an inoculation experiment to evaluate their pathogenicity and host range. Ageratina adenophora harboured diverse necrotrophic pathogens; its communities of endophytes and leaf spot pathogens were different in composition and shared only a small number of fungal species. In the pathogen communities of local plant hosts, 21% of the operational taxonomic units (OTUs), representing 50% of strains, also occurred as leaf spot pathogens and/or endophytes of A. adenophora. The local pathogen community was more similar to the endophytes than to the pathogens of A. adenophora. The inoculation experiment showed that local pathogens could infect A. adenophora leaves asymptomatically and that local plant hosts were susceptible to both A. adenophora endophytes and pathogens. Ageratina adenophora is a highly competent host for local pathogens, and its asymptomatic latent pathogens are fungi primarily shared with local neighbours. This poses challenges for understanding the long-term ecological consequences of plant invasion.

Hot deformation behavior of GCr15（ASTM 52100） steel was investigated using single-hit compression tests on Gleeble-1500 simulator at the temperature range of 850-1 100 ℃ and strain rate range of 0.1-10 s-1.The flow stress constitutive equation of GCr15 steel during hot deformation was determined by stress-strain curves analysis on the basis of the hyperbolic sine equation.And the models of dynamic recrystallization fraction and dynamic recrystallization grain size of GCr15 steel were established by the measured curves and microstructure observation in different experimental conditions.The mean activation energy and the time exponent of dynamic recrystallization kinetics equation in the range of experimental conditions were determined to be 356.2 kJ/mol and 2.12,respectively.Meanwhile,the flow stress model was also established by the method of allocating flow stress curve with three main stress values,the saturation stress,the steady state stress and the stress when strain is 0.1.The flow stress curves predicted by the developed models under different deformation conditions are in good agreements with the measured ones.

Aim： To investigate the metabolite changes caused by simvastatin or fenofibrate intervention in diet-induced hyperlipidemia rats using a GC-MS-based metabolomic profiling approach. Methods： SD rats were fed with high-lipid diet for 4 weeks to induce hyperlipidemia, then the rats were fed with normal diet, and orally administered with simvastatin （10 mg.kg-1.d-1） or fenofibrate （150 mg.kg-1.d-1） for 2 weeks. Blood samples were collected once a week, and potential biomarkers were examined using commercial assay kits and a metabolomic approach. The metabolomics data were analyzed using a multivariate statistical technique and a principal component analysis （PCA）. Results： Oral administration of simvastatin or fenofibrate significantly decreased the plasma levels of total cholesterol （TC） and low- density lipoprotein （LDL） cholesterol and increased the plasma level of high-density lipoprotein （HDL） cholesterol in the hyperlipidemia rats. Plasma samples were scattered in the PCA scores plots in response to the diet and to the drugs administered. The main metabolites changed in the hyperlipidemia rats were cholesterol, creatinine, linoleic acid, β-hydroxybutyric acid, tyrosine, isoleucine and ornithine. The plasma level of creatinine was significantly lower in the simvastatin-treated rats than in the fenofibrate-treated rats. The plasma tyrosine concentration was declined following intake of high-lipid diet, which was reversed by fenobrate, but not by simvastatin. Conclusion： A series of potential biomarkers including tyrosine, creatinine, linoleic acid,β-hydroxybutyric acid and ornithine have been identified by metabolomic profiling, which may be used to identify the metabolic changes during hyperlipidemia progression.

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial （PCPT） and the European Randomized Study of Screening for Prostate Cancer （ERSPC） risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011. The estimated probabilities of prostate cancer and high-grade disease （Gleason 〉6） were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen （PSA） threshold of 4 ng m1-1, the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease （the area under the curve was 0.831 and 0.852, respectively, P〈O.01 for both）. Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration： the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml- z in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

Human carboxylesterase 2 (CES2), one of the most abundant hydrolases distributed in the small intestine, has been validated as a key therapeutic target to ameliorate the intestinal toxicity caused by irinotecan. This study aims to discover efficacious CES2 inhibitors from natural products and to characterize the inhibition potentials and inhibitory mechanisms of the newly identified CES2 inhibitors. Following high-throughput screening and evaluation of the inhibition potency of more than 100 natural products against CES2, it was found that the biflavones isolated from Ginkgo biloba displayed extremely potent CES2 inhibition activities and high specificity over CES1 (>1000-fold). Further investigation showed that ginkgetin, bilobetin, sciadopitysin and isoginkgetin potently inhibited CES2-catalyzed hydrolysis of various substrates, including the CES2 substrate-drug irinotecan. Notably, the inhibition potentials of four biflavones against CES2 were more potent than that of loperamide, a marketed anti-diarrhea agent used for alleviating irinotecan-induced intestinal toxicity. Inhibition kinetic analyses demonstrated that ginkgetin, bilobetin, sciadopitysin and isoginkgetin potently inhibited CES2-catalyzed fluorescein diacetate hydrolysis via a reversible and mixed inhibition manner, with K i values of less than 100 nM. Ensemble docking and molecular dynamics revealed that these biflavones could tightly and stably bind on the catalytic cavity of CES2 via hydrogen bonding and π -π stacking interactions, while the interactions with CES1 were awfully poor. Collectively, this study reports that the biflavones isolated from Ginkgo biloba are potent and highly specific CES2 inhibitors, which offers several promising lead compounds for developing novel anti-diarrhea agent to alleviate irinotecan-induced diarrhea.

Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines. However, the role of piRNAs in carcinogenesis has not been clearly defined. In the present study, a small interfering RNA inhibitor of piR651 was transfected into the NSCLC A549 and HCC827 cell lines to evaluate the effect of piR651 on cell growth. The association between piR651 expression and apoptosis was evaluated by flow cytometry and western blot analysis. Wound-healing and Transwell migration and invasion assays were used to determine the effect of piR651 on the migration and invasion of NSCLC cell lines. The results revealed that inhibition of piR651 inhibited cell proliferation and significantly increased the apoptotic rate compared with the negative control (NC), as well as altering the expression of apoptosis-associated proteins. There were fewer migrating and invading cells in the piR651-inhibited group than in the NC group in the Transwell assays. Furthermore, in the wound-healing assay, the wound remained wider in the piR651 inhibitor group, suggesting decreased cell migration compared with that in the NC group. The results of the present study demonstrate that piR651 potentially regulates NSCLC tumorigenic behavior by inhibiting cell proliferation, migration and invasion and by inducing apoptosis. Therefore, piR651 is a potential cancer diagnosis marker.

Previous in vivo and in vitro studies revealed that esculetin (Fig. 1 ) has anti-hepatitis B virus (anti-HBV) activity as well as a protective effect on liver damage caused by duck hepatitis B virus. We designed and synthesized a series of esculetin derivatives, introduced side chains containing various amino groups into site 7 of the parent structure, and synthesized C-4 and C-8 substituted derivatives with the goal of investigating their anti-HBV activities. In vitro anti-HBV activity was performed against HepG2.2.15 cells by using Enzyme-Linked Immunosorbent Assay(ELISA) kit and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay with lamivudine as the positive control. The results demonstrated that several compounds showed moderate anti-HBV activity, while the introduction of morpholine groups could significantly inhibit the expression of hepatitis B e antigen (HBeAg) and the introduction of the 2-methylimidazole group could significantly inhibit the expression of Hepatitis B surface antigen (HBsAg). Among all tested compounds, compound 4a demonstrated the best anti-HBeAg activity (IC 50  = 15.8 ± 4.2 μM), while compound 6d demonstrated the best anti-HBsAg activity (IC 50  = 21.4 ± 2.8 μM). Compounds 6b and 6c showed moderate anti-HBV activity and HBsAg inhibition. Compounds 4b showed moderate anti-HBV activity and an inhibitory effect on HBeAg. In addition, compounds 4a , 4c , 4d , 6b , 6c and 6d showed improved metabolic stability. This study provides useful guidance for the discovery of anti-HBV drugs, which merits further investigation. Graphical Abstract

Aim: To investigate the metabolite changes caused by simvastatin or fenofibrate intervention in diet-induced hyperlipidemia rats using a GC-MS-based metabolomic profiling approach. Methods: SD rats were fed with high-lipid diet for 4 weeks to induce hyperlipidemia, then the rats were fed with normal diet, and orally administered with simvastatin (10 mg·kg −1 ·d −1 ) or fenofibrate (150 mg·kg −1 ·d −1 ) for 2 weeks. Blood samples were collected once a week, and potential biomarkers were examined using commercial assay kits and a metabolomic approach. The metabolomics data were analyzed using a multivariate statistical technique and a principal component analysis (PCA). Results: Oral administration of simvastatin or fenofibrate significantly decreased the plasma levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol and increased the plasma level of high-density lipoprotein (HDL) cholesterol in the hyperlipidemia rats. Plasma samples were scattered in the PCA scores plots in response to the diet and to the drugs administered. The main metabolites changed in the hyperlipidemia rats were cholesterol, creatinine, linoleic acid, β-hydroxybutyric acid, tyrosine, isoleucine and ornithine. The plasma level of creatinine was significantly lower in the simvastatin-treated rats than in the fenofibrate-treated rats. The plasma tyrosine concentration was declined following intake of high-lipid diet, which was reversed by fenobrate, but not by simvastatin. Conclusion: A series of potential biomarkers including tyrosine, creatinine, linoleic acid, β-hydroxybutyric acid and ornithine have been identified by metabolomic profiling, which may be used to identify the metabolic changes during hyperlipidemia progression.

The interactions of major pests with their natural enemies in the environment of intercropped orchards have recently received much attention. In this study, eight aromatic plant species, namely Mentha canadensis L. (Lamiaceae), Tagetes patula L. (Asteraceae), Ocimum basilicum L. (Lamiaceae), Satureja hortensis L. (Lamiaceae), Agerarum houstonianum Mill (Asteraceae), Ocimum  ×  citriodorum Vis. (Lamiaceae), Nepeta cataria L. (Lamiaceae) and Centaurea cyanus L. (Asteraceae), were used to evaluate the effects of intercropping with aromatic plants on Comstock mealybugs ( Pseudococcus comstocki Kuwana) and their natural predators. The effects of meteorological factors on Comstock mealybug were also investigated. Compared with natural grass or clean tillage plots, intercropping with aromatic plants significantly reduced the abundance of Comstock mealybugs and increased that of their predators, thereby increasing the ratio of natural enemies to pests. In the intercropped plots, the individual number Comstock mealybugs was reduced by 22.71–76.76 %; the peak period for Comstock mealybugs was delayed by 10–20 days, and the peak period for their predators was advanced by 0–60 days. The presence of Comstock mealybugs was significantly positively correlated with precipitation in all plots and significantly negatively correlated with sunshine duration. In conclusion, intercropping with aromatic plants significantly reduced the individual number of Comstock mealybugs, especially intercropping with A. houstonianum . Furthermore, this effect was enhanced during the summer months with high precipitation levels and long periods of sunshine.

There is increasing interest in the use of vegetation such as aromatic plants as intercrops to biologically control insect pests in agroecosystems and orchard ecosystems. Understanding the mechanisms underlying the repellent effects of aromatic plants on orchard pests (e.g., scarabaeid pests) can lead to improved application of intercropping cultivation practices in orchards. We tested eight intercropping treatments, each containing a different species of aromatic plant, in a pear orchard, along with a natural grass treatment and a clean tillage (control) treatment. The results showed that intercropping reduced the annual cumulative number and abundance of scarab beetles relative to the control. The annual dynamics of scarab populations were also significantly altered where intercrops were used. However, with the exception of Ichneunmonidae , the natural parasites of scarabs showed no preference for the aromatic plants. A correlation analysis indicated that the reduction in some of the scarab beetle species was related to the abundance of certain specific natural enemy species. In addition, the diversity, evenness and degree of dominance of natural enemy species may have contributed to the decrease in scarab populations. This study shows that intercropped aromatic plants can be applied to control the scarab beetles in orchard ecosystems, but that effects vary across aromatic plant species.