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Flavonols are widely distributed plant metabolites that inhibit microbial growth. Yet many pathogens cause disease in flavonol-containing plant tissues. We investigated how Sclerotinia sclerotiorum, a necrotrophic fungal pathogen that causes disease in a range of economically important crop species, is able to successfully infect flavonol-rich tissues of Arabidopsis (Arabidopsis thaliana). Infection of rosette stage Arabidopsis with a virulent S. sclerotiorum strain led to the selective hydrolysis of flavonol glycosidic linkages and the inducible degradation of flavonol aglycones to phloroglucinol carboxylic and phenolic acids. By chemical analysis of fungal biotransformation products and a search of the S. sclerotiorum genome sequence, we identified a quercetin dioxygenase gene (QDO) and characterized the encoded protein, which catalyzed cleavage of the flavonol carbon skeleton. QDO deletion lines degraded flavonols with much lower efficiency and were less pathogenic on Arabidopsis leaves than wild-type S. sclerotiorum, indicating the importance of flavonol degradation in fungal virulence. In the absence of QDO, flavonols exhibited toxicity toward S. sclerotiorum, demonstrating the potential roles of these phenolic compounds in protecting plants against pathogens. [ABSTRACT FROM AUTHOR]

Electrochemical generation of free nitric oxide (NO) from nitrite (NO2-) catalyzed by iron meso-tetrakis(4-Nmethylpyridiniumyl)porphyrin, [FeIII(TMPyP)]5+, has been developed in this study. To obtain free NO, a cathodic electrolysis and an anodic electrolysis were performed in two connected flow electrolytic cells in sequence. The flow electrolytic cell upstream was used for cathodic electrolysis, where the solution of [FeIII(TMPyP)]5+ and NO2- was reduced at -0.25 V (vs Ag/AgCI) into [FeII(NO2-)2(TMPyP)]2+ and [FeII(NO)(TMPyP)]4+in sequence. The flow electrolytic cell downstream was utilized for anodic electrolysis, where [FeII(NO)(TMPyP)]4+ formed from the upstream cell was oxidized at +0.40 V (vs Ag/AgCI) into [FeIII(TMPyP)]5+ and free NO. Finally, NO was bubbled out from anodic electrolyte by argon gas. The mechanism and the optimum conditions for electrochemical generation of NO from NO2- catalyzed by [FeIII(TMPyP)]5+ were studied in detail by voltammetric and spectroelectrochemical methods. [ABSTRACT FROM AUTHOR]

Understanding the interplay between ordered structures and substrate curvature is an interesting problem with versatile applications, including functionalization of charged supramolecular surfaces and modern microfluidic technologies. In this work, we investigate the two-dimensional packing structures of charged particles confined on a pinched sphere. By continuously pinching the sphere, we observe cleavage of elongated scars into pleats, proliferation of disclinations, and subsequently, emergence of a depletion zone at the negatively curved waist that is completely void of particles. We systematically study the geometrics and energetics of the depletion zone, and reveal its physical origin as a finite size effect, due to the interplay between Coulomb repulsion and concave geometry of the pinched sphere. These results further our understanding of crystallography on curved surfaces, and have implications in design and manipulation of charged, deformable interfaces in various applications. [ABSTRACT FROM AUTHOR]

Our electrochemical cell consisted of a ferrocene-included hemispherical nitrobenzene (NB) droplet on the glassy carbon (GC) electrode which was immersed in the aqueous solution including sodium sulfate and sodium dodecyl sulfate (SDS). When an air bubble was injected near the boundary between the oil and the aqueous phase, it stayed at the top of the hemisphere on the boundary so that the lower half of the bubble was put in oil and the other half was in water. From the force balance of surface tension and buoyancy of the bubble, the bubble took an energetic minimum at the interface. It sank into the oil phase when ferrocene in the oil was electrochemically oxidized through the GC electrode by the three-phase boundary reaction. The electrochemical reduction caused the bubble to move back toward the aqueous phase. The motion of the bubble was synchronized with the redox reaction of ferrocene. The potential step oxidation showed such a rapid response that the motion could not be attributed to diffusion of ferricenium ion from the three-phase boundary to the bubble. Our idea of explaining the rapidity was the translational motion of the SDS layer along the boundary, which was driven by the difference in the surface concentration of SDS caused by the electrochemical generation of the ferricenium ion. The motion of the SDS layer was demonstrated by the shrinkage of the oil layer spread on the water surface when SDS solution was dropped on the oil layer. The spreading velocity was close to the velocity of propagating the oxidation of ferrocene to the bubble. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that exposure to polycyclic aromatic hydrocarbons (PAHs) and its derivatives is associated with an increased risk of skin cancers, and the carcinogenic effect of PAHs is thought to involve both tumor initiation and promotion. Whereas PAH tumor initiation is well characterized, the mechanisms involved in the tumor promotion of PAHs remain elusive. In the present study, we investigated the effects of PAHs on vascular endothelial growth factor (VEGF) expression by comparison of its induction between the active metabolite and its parent compound (B[a]PDE versus B[a]P) or between active compound and its relatively inactive analog (5-MCDE versus CDE). We found that exposure of cells to (±)-anti-benzo-[a]pyrene-7,g-diol-9,10-epoxide (B[a]PDE) or (±)-anti-5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE) led to marked induction of VEGF in Cl41 cells, whereas benzo[a]pyrene (B[a]P) or chrysene-l,2-dioi-3,4-epoxide (CDE) did not exhibit significant inductive effects. Exposure of cells to B[a]PDE and 5-MCDE did not induce HIF-1of activation, whereas AP-1 was significantly activated. Moreover, overexpression of TAM67 (a dominant-negative mutant c-Jun) dramatically blocked that VEGF induction. Electrophoretic mobility shift assay showed that AP-1 was only able to specifically recognize and bind to its AP-1 potential binding site within -1136 and -1115 of the VEGF promoter region. Site-directed mutation of this AP-1 binding site eliminated the VEGF transcriptional activity induced by B[a]PDE, suggesting that the AP-1 binding site between -1136 and -1115 in the VEGF promoter region is critical for VEGF induction by B[a]PDE. In addition, overexpression of Δp85 (a dominant-negative mutant PI-3K) impaired B[a]PDE- and 5-MCDE-induced VEGF induction. Considering our previous findings that PI-3K is an upstream mediator for c-Jun/AP-1 activation, we conclude that the VEGF induction by B[a]PDE and 5-MCDE is through PI-3K/AP-1-dependent and HIF-1α-independent pathways. These findings may help us to understand the mechanisms involved in PAH carcinogenic effects. [ABSTRACT FROM AUTHOR]

Hypoxia exposure during high-altitude expedition cause psychomotor impairment. Neuroimaging studies indicated that the impairment may be significantly associated with neuron loss and decreased regional homogeneity (ReHo) in several brain regions, suggesting the neural functionality in these regions may be utilized to predict psychomotor impairment under exposure. In this study, 69 subjects come from Shaanxi-Tibet immigrant cohort. Reaction time (RT) tasks were performed to measure the subject's psychomotor function before and after 2-year high-altitude exposure. For each individual, the RT differences between pre-exposure and post-exposure were calculated, which were referred to as "targets" in model establishment. Rs-fMRI data were acquired at the same time with RT tasks. For each individual, the map of ReHo alteration was generated, from which the patterns would be recognized. A pattern recognition procedure was utilized to train and test the predictive models. Two different cross-validation strategies were utilized to evaluate the model performance: leave-one-out cross-validation and four-fold cross-validation. For the models displaying significant R2 and MSE, weight maps were built. As a result, the predictive models were able to decode the changes of simple and recognition reaction time from the alterations of brain activation under the exposure. The regions with highest contributions to the predictions were bilateral putamen and bilateral pallidum, suggesting that predictions were mainly based on the patterns concentrated in these regions. This study was a proof of concept study designed to examine whether individual-level psychomotor impairment under highaltitude exposure could be predicted by a combination of pattern recognition approach and neuroimaging data. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rapid economic development in China has produced serious ecological, environmental, and health problems. Neurotoxicity has been recognized as a major public health problem. The Chinese government, research institutes, and scientists conducted extensive studies concerning the source, characteristics, and mechanisms of neurotoxicants. OBJECTIVES: This paper presents, for the first time, a comprehensive history and review of major sources of neurotoxicants, national bodies/legislation engaged, and major neurotoxicology research in China. METHODS: Peer-reviewed research and pollution studies by Chinese scientists from 1991 to 2015 were examined. PubMed, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were the major search tools. RESULTS: The central problem is an increased exposure to neurotoxicants from air and water, food contamination, e-waste recycling, and manufacturing of household products. China formulated an institutional framework and standards system for management of major neurotoxicants. Basic and applied research was initiated, and international cooperation was achieved. The annual number of peer-reviewed neurotoxicology papers from Chinese authors increased almost 30-fold since 2001. CONCLUSIONS: Despite extensive efforts, neurotoxicity remains a significant public health problem. This provides great challenges and opportunities. We identified 10 significant areas that require major educational, environmental, governmental, and research efforts, as well as attention to public awareness. For example, there is a need to increase efforts to utilize new in vivo and in vitro models, determine the potential neurotoxicity and mechanisms involved in newly emerging pollutants, and examine the effects and mechanisms of mixtures. In the future, we anticipate working with scientists worldwide to accomplish these goals and eliminate, prevent and treat neurotoxicity. [ABSTRACT FROM AUTHOR]

Rice blast, caused by Magnaporthe oryzae, is one of the most severe fungal diseases in rice worldwide. In this study, we developed methods to quickly and accurately detect and quantify M. oryzae in the pure cultures of the fungus, rice plants, and rice seed by using SYBR Green I of the real-time quantitative polymerase chain reaction (qPCR). Results of absolute qPCR show that Magnaporthe oryzae can be detected at as low as 6.9 x 10-5 ng of genomic DNA. Results also show that all 10 varieties of rice seed examined in this study contain this fungus, indicating that M. oryzae is generally widespread in rice seed. We report the quantification of DNA of M. oryzae in rice leaves collected in the field, instead of in the lab, using relative qPCR by using rice actin gene as a housekeeping gene. Our results show great practical significance because we would know the potential fungal infection even before planting. [ABSTRACT FROM AUTHOR]

miRNAs have been found to contribute to normal brain functions, nervous system diseases, as well as neurotoxicities induced by external agents. However, whether they are involved in lead-induced neurotoxicities is still not clear. To identify that, a lead-induced chronic neurotoxicity model of rats was built. Both miRNA microarray analysis and qRT-PCR were performed to determine the change of miRNA expression in hippocampus. Then 3 bioinformatics databases were used to analyze the relative target genes of these miRNA, which were further confirmed by qRT-PCR and Western blot. In the present study, lead exposure resulted in the changed expression of 7 miRNAs: miR-204, miR-211, miR-448, miR-449a, miR-34b, and miR-34c were greatly up-regulated while miR-494 was greatly down-regulated. Bioinformatics analysis results showed that the target genes of 6 up-regulated miRNAs were related to neural injury and neurodegeration, axon and synapse function, neural development and regeneration. Correspondingly, the expression levels of mature mRNAs and proteins of three target genes (Bcl-2, Itpr1, and Map2k1) were greatly repressed, verifying the results of bioinformatics analysis. Taken together, our results showed that the expression of several miRNAs reported to be associated with neurophysiological pathways and neurodegenerative diseases changed in rat hippocampus following chronic lead exposure. These miRNAs may play important roles in lead-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

MADS-box proteins, a well-conserved family of transcription factors in eukaryotic organisms, specifically regulate a wide range of cellular functions, including primary metabolism, cell cycle, and cell identity. However, little is known about roles of the MADS-box protein family in the fungal pathogen Sclerotinia sclerotiorum. In this research, the S. sclerotiorum MADS-box gene SsMADS was cloned; it encodes a protein that is highly similar to Mcm1 orthologs from Saccharomyces cerevisiae and other fungi, and includes a highly conserved DNA-binding domain. MADS is a member of the MADS box protein SRF (serum response factor) lineage. SsMADS function was investigated using RNA interference. Silenced strains were obtained using genetic transformation of the RNA interference vectors pS1-SsMADS and pSD-SsMADS. SsMADS expression levels in silenced strains were analyzed using RT-PCR. The results showed that SsMADS mRNA expression in these silenced strains was reduced to different degrees, and growth rate in these silenced strains was significantly decreased. Infecting tomato leaflets with silenced strains indicated that SsMADS was required for leaf pathogenesis in a susceptible host. Our results suggest that the MADS-box transcription factor SsMADS is involved in S. sclerotiorum growth and virulence. [ABSTRACT FROM AUTHOR]

The X-linked inhibitor of apoptosis protein (XIAP) is a well known potent inhibitor of apoptosis; however, it is also involved in other cancer cell biological behavior. In the current study, we discovered that XIAP and its E3 ligase played a crucial role in regulation of cyclin D1 expression in cancer cells.Wefound that deficiency of XIAP expression resulted in a marked reduction in cyclin D1 expression. Consistently, cell cycle transition and anchorage-independent cell growth were also attenuated in XIAP-deficient cancer cells compared with those of the parental wild-type cells. Subsequent studies demonstrated that E3 ligase activity within the RING domain of XIAP is crucial for its ability to regulate cyclin D1 transcription, cell cycle transition, and anchorage-independent cell growth by up-regulating transactivation of c-Jun/AP-1. Moreover, we found that E3 ligase within RING domain was required for XIAP inhibition of phosphatase PP2A activity by up-regulation of PP2A phosphorylation at Tyr- 307 in its catalytic subunit. Such PP2A phosphorylation and inactivation resulted in phosphorylation and activation of its downstream target c-Jun in turn leading to cyclinD1expression. Collectively, our studies uncovered a novel function of E3 ligase activity of XIAP in the up-regulation of cyclin D1 expression, providing significant insight into the understanding of the biomedical significance of overexpressed XIAP in cancer development, further offering a new molecular basis for utilizing XIAP E3 ligase as a cancer therapeutic target [ABSTRACT FROM AUTHOR]

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP-/- HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP DBIR, both of which have intact RING domain, restored b-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP DRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification. [ABSTRACT FROM AUTHOR]

X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In this study, we found that a deficiency of XIAP expression in human cancer cells by either knock-out or knockdown leads to a marked reduction in β-actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells compared with parental wildtype cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depends on its interaction with the Rho GDP dissociation inhibitor (RhoGDI) via the XIAP RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion and offer a further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic properties. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is an essential trace element. It is known to have various functions, such as participating in enzymatic synthesis, and promoting hematopoiesis. On the other hand, it can cause toxic injury upon excess intake. However, toxic effects and its mechanism on glial cells are unclear. In the present study, we demonstrated that MnCl2 can activate microglia, and that this can cause dopaminergic neuronal injury. Investigation of the underlying mechanisms showed that inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) was induced and highly expressed following Mn treatment. Moreover, pretreatment with S-methylisothiourea (SMT. iNOS inhibitor), Mn-induced iNOS expression and dopaminergic neuronal injury were partly reverse. Pretreatment with minocycline (microglia activation inhibitor), Mn-induced activation of microglia and dopaminergic neuronal injury was partly reverse. Taken together, our results showed that Mn can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, and these inflammatory factors can cause dopaminergic neuronal injury. SMT and minocycline prevent Mn-induced dopaminergic neuronal injury. [ABSTRACT FROM AUTHOR]

Abstract  SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long-term exposure of arsenite leads to human skin cancer. However, the exact mechanisms of arsenite-induced human skin carcinogenesis remain to be defined. OBJECTIVES: In this study, we investigated the potential role of PI-3K/Akt/cyclin D1in the transformation of human keratinocytic cells upon arsenite exposure. METHODS: We used the soft agar assay to evaluate the cell transformation activity of arsenite exposure and the nude mice xenograft model to determine the tumorigenesis of arsenite-induced transformed cells. We used the dominant negative mutant and gene knockdown approaches to elucidate the signaling pathway involved in this process. RESULTS: Our results showed that repeated long-term exposure of HaCat cells to arsenite caused cell transformation, as indicated by anchorage-independent growth in soft agar. The tumorigenicity of these transformed cells was confirmed in nude mice. Treatment of cells with arsenite also induced significant activation of PI-3K and Akt, which was responsible for the anchorage-independent cell growth induced by arsenite exposure. Furthermore, our data also indicated that cyclin D1 is an important downstream molecule involved in PI-3K/Akt-mediated cell transformation upon arsenite exposure based on the facts that inhibition of cyclin D1 expression by dominant negative mutants of PI-3K, and Akt, or the knockdown of the cyclin D1 expression by its specific siRNA in the HaCat cells resulted in impairing of anchorage-independent growth of HaCat cells induced by arsenite. CONCLUSION: Our results demonstrate that PI-3K/Akt-mediated cyclin D1 expression is at least one key event implicated in the arsenite human skin carcinogenic effect. [ABSTRACT FROM AUTHOR]

The article offers information on the increase of lead poisoning cases in China in 2011. In early January, 228 children had blood lead concentrations higher than 100 microgram per liter (µg/L) in Huaining County, Anhui Province and 23 children had blood lead concentrations higher than 250 µg/L had to be treated in hospital. From 2009-2011, lead poisoning in some provinces of China has impacted more than 4,000 children.

Manganese is an essential trace element required for normal development and bodily functions. However, exposure of the brain to excessive amounts of manganese results in neurotoxicity. Although previous studies examining manganese neurotoxicity have focused on neuronal injury, especially direct injury to dopaminergic neurons, the effects of manganese-induced neurotoxicity on glial cells have not been reported. The current study was designed to examine the effect of manganese on microglial activation, and the underlying mechanism of manganese-induced dopaminergic neuronal injury in vivo. We established an animal model of manganism by intrastriatal injection of MnCl2·4H2O into male Sprague-Dawley rats. One day after administration of manganese, a few microglial cells in the substantia nigra (SN) were activated, although the number of tyrosine hydroxylase (TH)–immunoreactive neurons in the SN was unaffected. Seven days after administration of manganese, a marked reduction in the number of TH-immunoreactive neurons was observed in the SN, and the majority of microglial cells were activated. We found that manganese upregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α) gene expression, as well as iNOS, TNF-α, and interleukin-1β (IL-1β) protein levels in the SN. Furthermore, treatment with minocycline, an inhibitor of microglial activation, attenuated microglial activation and mitigated IL-1β, TNF-α, and iNOS production as well as dopaminergic neurotoxicity induced by manganese. These results suggested that dopaminergic neurons could be damaged by manganese neurotoxicity, and that the activated microglial cells and their associated activation products played an important role in this neurodegenerative process. [ABSTRACT FROM AUTHOR]