Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish.

There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 µg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 µg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

Omics data reveal the unusual asexual-fruiting nature and secondary metabolic potentials of the medicinal fungus Cordyceps cicadae.

BACKGROUND: Ascomycete Cordyceps species have been using as valued traditional Chinese medicines. Particularly, the fruiting bodies of Cordyceps cicadae (syn. Isaria cicadae) have long been utilized for the treatment of chronic kidney disease. However, the genetics and bioactive chemicals in this fungus have been largely unexplored. RESULTS: In this study, we performed comprehensive omics analyses of C. cicadae, and found that, in contrast to other Cordyceps fungi, C. cicadae produces asexual fruiting bodies with the production of conidial spores instead of the meiotic ascospores. Genome sequencing and comparative genomic analysis indicate that the protein families encoded by C. cicadae are typical of entomopathogenic fungi, including the expansion of proteases and chitinases for targeting insect hosts. Interestingly, we found that the MAT1-2 mating-type locus of the sequenced strain contains an abnormally truncated MAT1-1-1 gene. Gene deletions revealed that asexual fruiting of C. cicadae is independent of the MAT locus control. RNA-seq transcriptome data also indicate that, compared to growth in a liquid culture, the putative genes involved in mating and meiosis processes were not up-regulated during fungal fruiting, further supporting asexual reproduction in this fungus. The genome of C. cicadae encodes an array of conservative and divergent gene clusters for secondary metabolisms. Based on our analysis, the production of known carcinogenic metabolites by this fungus could be potentially precluded. However, the confirmed production of oosporein raises health concerns about the frequent consumption of fungal fruiting bodies. CONCLUSIONS: The results of this study expand our knowledge of fungal genetics that asexual fruiting can occur independent of the MAT locus control. The obtained genomic and metabolomic data will benefit future investigations of this fungus for medicinal uses.

Trajectory and genomic determinants of fungal-pathogen speciation and host adaptation.

Much remains unknown regarding speciation. Host-pathogen interactions are a major driving force for diversification, but the genomic basis for speciation and host shifting remains unclear. The fungal genus Metarhizium contains species ranging from specialists with very narrow host ranges to generalists that attack a wide range of insects. By genomic analyses of seven species, we demonstrated that generalists evolved from specialists via transitional species with intermediate host ranges and that this shift paralleled insect evolution. We found that specialization was associated with retention of sexuality and rapid evolution of existing protein sequences whereas generalization was associated with protein-family expansion, loss of genome-defense mechanisms, genome restructuring, horizontal gene transfer, and positive selection that accelerated after reinforcement of reproductive isolation. These results advance understanding of speciation and genomic signatures that underlie pathogen adaptation to hosts.

Linkage of oxidative stress and mitochondrial dysfunctions to spontaneous culture degeneration in Aspergillus nidulans.

Filamentous fungi including mushrooms frequently and spontaneously degenerate during subsequent culture maintenance on artificial media, which shows the loss or reduction abilities of asexual sporulation, sexuality, fruiting, and production of secondary metabolites, thus leading to economic losses during mass production. To better understand the underlying mechanisms of fungal degeneration, the model fungus Aspergillus nidulans was employed in this study for comprehensive analyses. First, linkage of oxidative stress to culture degeneration was evident in A. nidulans. Taken together with the verifications of cell biology and biochemical data, a comparative mitochondrial proteome analysis revealed that, unlike the healthy wild type, a spontaneous fluffy sector culture of A. nidulans demonstrated the characteristics of mitochondrial dysfunctions. Relative to the wild type, the features of cytochrome c release, calcium overload and up-regulation of apoptosis inducing factors evident in sector mitochondria suggested a linkage of fungal degeneration to cell apoptosis. However, the sector culture could still be maintained for generations without the signs of growth arrest. Up-regulation of the heat shock protein chaperones, anti-apoptotic factors and DNA repair proteins in the sector could account for the compromise in cell death. The results of this study not only shed new lights on the mechanisms of spontaneous degeneration of fungal cultures but will also provide alternative biomarkers to monitor fungal culture degeneration.

Genome sequencing and comparative transcriptomics of the model entomopathogenic fungi Metarhizium anisopliae and M. acridum.

Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ~30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ~16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogeneous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties.

Multidimensional occurrence and diet risk of emerging contaminants in freshwater with urban agglomerations.

Freshwater systems near highly urbanized areas are extremely susceptible to emerging contaminants (ECs), yet their stereoscopic persistence in aquatic ecosystems and related risks remain largely unknown. Herein, we characterized the multi-mediums distribution of 63 ECs in Baiyangdian Lake, the biggest urban lake in the North of China. We identified variations in the seasonal patterns of aquatic EC levels, which decreased in water and increased in sediment from wet to dry seasons. Surprisingly, higher concentrations and a greater variety of ECs were detected in reeds than in aquatic animals, indicating that plants may contribute to the transferring of ECs. Source analysis indicated that human activity considerably affected the distribution and risk of ECs. The dietary risk of ECs is most pronounced among children following the intake of aquatic products, especially with a relatively higher risk associated with fish consumption. Besides, a comprehensive scoring ranking method was proposed, and 9 ECs, including BPS and macrolide antibiotics, are identified as prioritized control pollutants. These findings highlight the risks associated with aquatic ECs and can facilitate the development of effective management strategies.

The neurobehavioral impacts of typical antibiotics toward zebrafish larvae.

Due to the widely usage in livestock, aquaculture and clinics, antibiotic residues are existed in aqueous environments and their potential toxicity to aquatic organisms is concerning. Here, we used zebrafish as the model to investigate the neurotoxicity and involved mechanism of seven antibiotics that were frequently detected in surface waters. The results revealed that the short-term exposure to clarithromycin (CLA), chlortetracycline (CTC) and roxithromycin (ROX) induced behavioral effects, with effective concentration of 1 µg/L (CTC and ROX) and 100 µg/L (CLA, CTC and ROX) respectively. A significant decrease in the travel distance and velocity as well as an increase in turn angle was measured. TUNEL assay identified increased cell apoptosis in brain sections of larvae exposed to three neurotoxic antibiotics, which raised the possibility that the behavioral symptoms were associated with neural damage. Transcriptome sequencing showed that the three antibiotics could affect the nervous system of zebrafish including the alteration of synaptogenesis and neurotransmission. Additionally, ROX and CTC affected pathways involved in mitochondrial stress response and endocrine system in zebrafish larvae. Besides, BDNF, ASCL1, and CREBBP are potential upstream regulatory factors that mediated these impacts. These findings indicated that exposure of CTC, ROX and CLA may cause abnormal behavior toward zebrafish larvae under environmental relevant concentration and revealed the potential role of neural cell apoptosis and synaptogenesis signaling in mediating this effect.

Occurrence and distribution of antibiotic resistant bacteria and genes in the Fuhe urban river and its driving mechanism.

Antibiotic resistance genes (ARGs) in urban rivers can affect human health via the food chain and human pathogenic bacteria diffusion. Sediment can be a sink for ARGs, causing second sources of ARG contamination through diffusion. Therefore, we evaluated the effects of total petroleum hydrocarbons (TPHs) and phytoplankton on the distribution of the ARGs in the sediment and water of Fuhe river in Baoding city, China. The ARGs and human pathogenic bacteria in urban river were analyzed, and the phytoplankton and bacterial abundance, TPH, and physicochemical parameters ranked using the partial least squares path modelling (PLS-PM) and aggregated boosted tree (ABT) analysis. The main ARGs in Fuhe river sediment were sulfonamide and tetracycline resistance genes, with sul2 exhibiting the highest level. The main human pathogenic bacteria in the pathogens pool were Clostridium, Bacillus and Burkholderiaceae, with Clostridium demonstrating a positive correlation with SulAfolP01. The PLS-PM analysis confirmed that, among the multiple drivers, water physicochemical factors, TPH, phytoplankton, and heavy metals positively and directly affected the ARG profiles in sediment while sediment heavy metals and bacterial communities did the similar effect. These factors (nutrient factors, heavy metals, and TPH) in water and sediment posed the opposite total effect on ARGs in the sediment, suggesting medium factors should have a conclusive effect on the distribution of ARGs in the sediment. The ABT analysis showed that dissolved oxygen (DO), total nitrogen (TN) and Chlorophyta were the most important factors affecting the ARGs distribution in the water, while TN affected the distribution of the genes in the sediment.

MiR-4652-5p Targets RND1 to Regulate Cell Adhesion and Promote Lung Squamous Cell Carcinoma Progression.

Lung squamous cell carcinoma (LUSC) is one subtype of non-small-cell lung cancer, whose pathogenesis has not been fully understood. Exploring molecular mechanisms of LUSC helps a lot with the development of LUSC novel therapy. Hence, our study aims to investigate novel molecular mechanisms. Differentially expressed miRNAs and mRNAs were acquired from The Cancer Genome Atlas database. A series of assays were applied to test cell functions, including qRT-PCR to analyze RND1 and miR-4652-5p expression, dual-luciferase reporter gene assay to verify the targeting relationship between these two genes, cell counting kit-8 and colony formation assays to evaluate the ability of LUSC cells to proliferate, transwell to examine the migratory and invasive abilities, and western blot to test expression of RND1 and cell adhesion-related proteins. RND1 was lowly expressed while miR-4652-5p was highly expressed in LUSC cells. The correlation between these two genes was significantly negative and miR-4652-5p could downregulate RND1 expression. Additionally, cellular function assays validated that RND1 suppressed LUSC cells to proliferate, migrate, and invade. Besides, this gene might also affect cell adhesion. Furthermore, rescue assay suggested that miR-4652-5p downregulated RND1 expression to promote the progression of LUSC cells. Together, miR-4652-5p targeted RND1 to modulate cell adhesion and the progression of LUSC cells.

Ibrolipim attenuates high glucose-induced endothelial dysfunction in cultured human umbilical vein endothelial cells via PI3K/Akt pathway.

OBJECTIVE: Endothelial dysfunction is a key event in the onset and progression of atherosclerosis associated with diabetes. Increasing cell apoptosis may lead to endothelial dysfunction and contribute to vascular complications. Therefore, we aimed to elucidate the possible role and mechanism of ibrolipim in preventing endothelial dysfunction induced by high glucose. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured respectively under normal glucose level (5.5mM), high glucose level (33mM), and high glucose level with ibrolipim treatment. Endothelial dysfunction was identified by the expression of ET-1 and vWF through reverse transcription PCR (RT-PCR). HUVECs apoptosis was assessed by fluorescent staining with Hoechst 33258. Akt activity was analyzed by western blot. RESULTS: High glucose condition significantly increased the rate of apoptotic cells, weakened cell viability, and decreased the expression of ET-1 and vWF. Ibrolipim treatment significantly attenuated these alterations of endothelial dysfunction. The lower concentrations (2, 4, 8 microM) of ibrolipim inhibited apoptosis of cultured HUVECs, improved cell viability, down-regulated the mRNA levels of ET-1, vWF, and attenuated the cytotoxicity; however, higher concentration (16, 32 microM) of ibrolipim aggravated the damage of HUVECs cultured under high glucose level. Meanwhile, high glucose induced a decrease of Akt activity which led to apoptosis, and ibrolipim prevented the decrease and attenuated apoptotic effect induced by high glucose. Furthermore, the PI3K inhibitor LY294002 significantly abolished the anti-apoptotic effect of ibrolipim, and decreased Akt phosphorylation. Although, the expression of Akt mRNA and total protein were not altered in cultured HUVECs. CONCLUSION: Ibrolipim at lower concentrations can inhibit high glucose-induced apoptosis in cultured HUVECs, which might be related to the alternation of Akt activity. Ibrolipim has the potential to attenuate endothelial dysfunction and lower the risk of diabetes-associated vascular diseases. And it might be a therapeutic agent for diabetic vascular complications.

Effects of selenium on the antioxidant enzymes response of Neocaridina heteropoda exposed to ambient nitrite.

The effects of dietary Selenium (Se) supplementation on muscle superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities and haemolymph superoxide anions (O(2)-) of Neocaridina heteropoda exposed to ambient nitrite were investigated. The results showed supplementation of Se in diet could enhance the resistance of shrimp to low concentration ambient nitrite. The results demonstrated that Se might have a potentially useful role as an effective antioxidant and resistance to aqueous nitrite in shrimp and the effect of the organic Se was better than that of the inorganic Se.

Congruence Amidst Discordance between Sequence and Protein-Content Based Phylogenies of Fungi.

Amid the genomic data explosion, phylogenomic analysis has resolved the tree of life of different organisms, including fungi. Genome-wide clustering has also been conducted based on gene content data that can lighten the issue of the unequal evolutionary rate of genes. In this study, using different fungal species as models, we performed phylogenomic and protein-content (PC)-based clustering analysis. The obtained sequence tree reflects the phylogenetic trajectory of examined fungal species. However, 15 PC-based trees constructed from the Pfam matrices of the whole genomes, four protein families, and ten subcellular locations largely failed to resolve the speciation relationship of cross-phylum fungal species. However, lifestyle and taxonomic associations were more or less evident between closely related fungal species from PC-based trees. Pairwise congruence tests indicated that a varied level of congruent or discordant relationships were observed between sequence- and PC-based trees, and among PC-based trees. It was intriguing to find that a few protein family and subcellular PC-based trees were more topologically similar to the phylogenomic tree than was the whole genome PC-based phylogeny. In particular, a most significant level of congruence was observed between sequence- and cell wall PC-based trees. Cophylogenetic analysis conducted in this study may benefit the prediction of the magnitude of evolutionary conservation, interactive associations, or networking between different family or subcellular proteins.

The change of accumulation of heavy metal drive interspecific facilitation under copper and cold stress.

Plant diversity has important functions in ecosystem productivity overyielding and community stability. Little is known about the mechanism causing productivity overyielding and stability under harsh conditions. This study investigated the photosynthetic response and subcellular distribution of uni- and co-cultured duckweeds (Lemna aequinoctialis and Spirodela polyrhiza) under excess copper (1.0 mg/L) and low temperature (5 °C) conditions. The results showed that the growth of uni-cultured L. aequinoctialis was not different from that of uni-cultured S. polyrhiza across copper treatments at control temperature (25 °C). The growth rate of L. aequinoctialis increased by 55.5 % under excess copper concentration when it coexisted with S. polyrhiza, compared with uni-culture. Subcellular distributions of copper were predominantly distributed in cell walls. S. polyrhiza accumulated more copper in cell walls than L. aequinoctialis under uni-cultured condintion at excess copper concentration. Co-cultured S. polyrhiza increased copper accumulation in cell walls of co-cultured L. aequinoctialis to decrease toxicity at excess copper concentration, compared with L. aequinoctialis. Low temperature increased copper toxicity, with duckweeds having lower growth rate and photosynthetic activities (Fv/Fm). The L. aequinoctialis growth rate in co-culture was higher than in uni-culture under excess copper concentration and low temperature conditions, indicating that S. polyrhiza decreased the copper toxicity for L. aequinoctialis. The photosynthetic activity (Fv/Fm) of co-cultured L. aequinoctialis was higher than that of uni-cultured L. aequinoctialis exposed to excess copper concentration at low temperature. The community that formed by co-culturing S. polyrhiza and L. aequinoctialis produced more biomass by avoiding the toxicity of excess copper through heavy metal compartmentalization and photosynthetic activities.

GO-2D: identifying 2-dimensional cellular-localized functional modules in Gene Ontology.

BACKGROUND: Rapid progress in high-throughput biotechnologies (e.g. microarrays) and exponential accumulation of gene functional knowledge make it promising for systematic understanding of complex human diseases at functional modules level. Based on Gene Ontology, a large number of automatic tools have been developed for the functional analysis and biological interpretation of the high-throughput microarray data. RESULTS: Different from the existing tools such as Onto-Express and FatiGO, we develop a tool named GO-2D for identifying 2-dimensional functional modules based on combined GO categories. For example, it refines biological process categories by sorting their genes into different cellular component categories, and then extracts those combined categories enriched with the interesting genes (e.g., the differentially expressed genes) for identifying the cellular-localized functional modules. Applications of GO-2D to the analyses of two human cancer datasets show that very specific disease-relevant processes can be identified by using cellular location information. CONCLUSION: For studying complex human diseases, GO-2D can extract functionally compact and detailed modules such as the cellular-localized ones, characterizing disease-relevant modules in terms of both biological processes and cellular locations. The application results clearly demonstrate that 2-dimensional approach complementary to current 1-dimensional approach is powerful for finding modules highly relevant to diseases.

Divergent and Convergent Evolution of Fungal Pathogenicity.

Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen-host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus-animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation.

Diallyl disulfide selectively causes checkpoint kinase-1 mediated G2/M arrest in human MGC803 gastric cancer cell line.

Previous studies have shown that diallyl disulfide (DADS), a naturally occurring anticancer agent in garlic, arrested human gastric cancer cells (MGC803) in the G2/M phase of the cell cycle. Due to the importance of cell cycle redistribution in DADS-mediated anticarcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. In the present study, the northern blot analysis showed that mRNA expression of for Chkl and Chk2 was unchanged. Notably, DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, activated phospho-ATR (ATM-RAD3-related gene), and dowregulated CDC25C and cyclin B1 expression. Furthermore, CDC25C was immunoprecipitated by anti-Chk1 but not anti-Chk2. Results of the overexpression and knockdown studies, showed that Chk1 but not Chk2 regulated the DADS-induced G2/M arrest of MGC803 cells. The overexpression of Chk1 resulted in significantly increased DADS-induced G2/M arrest, increased DADS-induced Chk1 phosphorylation and inhibited CDC25C expression. Knockdown of Chk1 reduced DADS­induced G2/M arrest and blocked the DADS-induced inhibition of CDC25C and cyclin B1 expression. These results suggested that Chk1 is important in DADS­induced cell cycle G2/M arrest in the human MGC803 gastric cancer cell line. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/CDC25C/cyclin B1.

Transcriptional profiling of midgut immunity response and degeneration in the wandering silkworm, Bombyx mori.

BACKGROUND: Lepidoptera insects have a novel development process comprising several metamorphic stages during their life cycle compared with vertebrate animals. Unlike most Lepidoptera insects that live on nectar during the adult stage, the Bombyx mori silkworm adults do not eat anything and die after egg-laying. In addition, the midguts of Lepidoptera insects produce antimicrobial proteins during the wandering stage when the larval tissues undergo numerous changes. The exact mechanisms responsible for these phenomena remain unclear. PRINCIPAL FINDINGS: We used the silkworm as a model and performed genome-wide transcriptional profiling of the midgut between the feeding stage and the wandering stage. Many genes concerned with metabolism, digestion, and ion and small molecule transportation were down-regulated during the wandering stage, indicating that the wandering stage midgut loses its normal functions. Microarray profiling, qRT-PCR and western blot proved the production of antimicrobial proteins (peptides) in the midgut during the wandering stage. Different genes of the immune deficiency (Imd) pathway were up-regulated during the wandering stage. However, some key genes belonging to the Toll pathway showed no change in their transcription levels. Unlike butterfly (Pachliopta aristolochiae), the midgut of silkworm moth has a layer of cells, indicating that the development of midgut since the wandering stage is not usual. Cell division in the midgut was observed only for a short time during the wandering stage. However, there was extensive cell apoptosis before pupation. The imbalance of cell division and apoptosis probably drives the continuous degeneration of the midgut in the silkworm since the wandering stage. CONCLUSIONS: This study provided an insight into the mechanism of the degeneration of the silkworm midgut and the production of innate immunity-related proteins during the wandering stage. The imbalance of cell division and apoptosis induces irreversible degeneration of the midgut. The Imd pathway probably regulates the production of antimicrobial peptides in the midgut during the wandering stage.

Feasibility and safety of magnetic-controlled capsule endoscopy system in examination of human stomach: a pilot study in healthy volunteers.

OBJECTIVE: To assess the feasibility and safety of magnetic-controlled capsule endoscopy (MCE) system for examination of human stomach. METHODS: This pilot study enrolled 34 healthy volunteers. All subjects swallowed the MCE and gas-producing powder for gastric distention. An external robot was used to generate magnetic field to manipulate MCE inside the stomach. The primary measurements included safety, gastric preparation, maneuverability and visualization of gastric mucosa. RESULTS: Gastric preparation and examination was well accepted by subjects and there were no adverse events. The examination in the stomach takes 43.8±10.0min (27-60). The cleanliness was evaluated as good in the 30 (88.2%) subjects and as moderate in 4 (11.8%) subjects. The distention of gastric cavity was evaluated as good in the 29 (85.3%) subjects and moderate in 5 (14.7%) subjects. Maneuverability of the MCE to movements of the guidance magnet robot was graded as good in 29 (85.3%) subjects and moderate in 5 (14.7%) subjects. More than 75% gastric mucosa was visualized in 27 (79.4%) subjects and 50% to 75% in 7 (20.6%) subjects. Visualization of the gastric cardia, fundus, body, angulus, antrum and pylorus was subjectively assessed as complete in 82.4%, 85.3%, 100.0%, 100.0%, 100.0% and 100.0%, respectively. Polyp and erosive lesions were found in 7 subjects. CONCLUSION: Magnetic-controlled capsule endoscopy used for examination of the human stomach is feasible and safe.

Genomic perspectives on the evolution of fungal entomopathogenicity in Beauveria bassiana.

The ascomycete fungus Beauveria bassiana is a pathogen of hundreds of insect species and is commercially produced as an environmentally friendly mycoinsecticide. We sequenced the genome of B. bassiana and a phylogenomic analysis confirmed that ascomycete entomopathogenicity is polyphyletic, but also revealed convergent evolution to insect pathogenicity. We also found many species-specific virulence genes and gene family expansions and contractions that correlate with host ranges and pathogenic strategies. These include B. bassiana having many more bacterial-like toxins (suggesting an unsuspected potential for oral toxicity) and effector-type proteins. The genome also revealed that B. bassiana resembles the closely related Cordyceps militaris in being heterothallic, although its sexual stage is rarely observed. A high throughput RNA-seq transcriptomic analysis revealed that B. bassiana could sense and adapt to different environmental niches by activating well-defined gene sets. The information from this study will facilitate further development of B. bassiana as a cost-effective mycoinsecticide.