The potential for oxathiapiprolin resistance in Phytophthora capsici was evaluated. The baseline sensitivities of 175 isolates to oxathiapiprolin were initially determinated and found to conform to a unimodal curve with a mean EC50 value of 5.61 × 10-4 μg/ml. Twelve stable oxathiapiprolin-resistant mutants were generated by fungicide adaptation in two sensitive isolates, LP3 and HNJZ10. The fitness of the LP3-mutants was found to be similar to or better than that of the parental isolate LP3, while the HNJZ10-mutants were found to have lost the capacity to produce zoospores. Taken together these results suggest that the risk of P. capsici developing resistance to oxathiapiprolin is moderate. Comparison of the PcORP1 genes in the LP3-mutants and wild-type parental isolate, which encode the target protein of oxathiapiprolin, revealed that a heterozygous mutation caused the amino acid substitution G769W. Transformation and expression of the mutated PcORP1-769W allele in the sensitive wild-type isolate BYA5 confirmed that the mutation in PcORP1 was responsible for the observed oxathiapiprolin resistance. Finally diagnostic tests including As-PCR and CAPs were developed to detect the oxathiapiprolin resistance resulting from the G769W point mutation in field populations of P. capsici.

Findings from this meta-analysis indicate that consumption of red and/or processed meat increase risk of stroke, in particular, ischemic stroke.

Pyrimorph is a novel fungicide with high activity against the plant pathogen Phytophthora capsici. We investigated the risk that P. capsici can develop resistance to pyrimorph. The baseline sensitivities of 226 P. capsici isolates, tested by mycelial growth inhibition, showed a unimodal distribution with a mean EC50 value of 1.4261 (±0.4002) µg/ml. Twelve pyrimorph-resistant mutants were obtained by repeated exposure to pyrimorph in vitro with a frequency of approximately 1×10−4. The resistance factors of the mutants ranged from 10.67 to 56.02. Pyrimorph resistance of the mutants was stable after 10 transfers on pyrimorph-free medium. Fitness in sporulation, cystospore germination, and pathogenicity in the pyrimorph-resistant mutants was similar to or less than that in the parental wild-type isolates. On detached pepper leaves and pepper plants treated with the recommended maximum dose of pyrimorph, however, virulence was greater for mutants with a high level of pyrimorph resistance than for the wild type. The results suggest that the risk of P. capsici developing resistance to pyrimorph is low to moderate. Among mutants with a high level of pyrimorph resistance, EC50 values for pyrimorph and CAA fungicides flumorph, dimethomorph, and mandipropamid were positively correlated. This indicated that point mutations in cellulose synthase 3 (CesA3) may confer resistance to pyrimorph. Comparison of CesA3 in isolates with a high level of pyrimorph resistance and parental isolates showed that an amino acid change from glutamine to lysine at position 1077 resulted in stable, high resistance in the mutants. Based on the point mutations, an allele-specific PCR method was developed to detect pyrimorph resistance in P. capsici populations.

BackgroundThough vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long‐term, low‐dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta‐analysis of prospective studies.Methods and ResultsPubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random‐effects model. The summary RR for the high‐versus‐low categories was 0.81 (95% CI: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and for each 20 μmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high‐versus‐low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies).ConclusionsThis meta‐analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

BackgroundImmunoglobulin A (IgA) and IgG are major components in human intestinal mucosal surface and sera, and IgA- or IgG-coated bacteria play a vital role in the intestinal homeostasis. However, the correlation of IgA, IgG and their coated bacteria with the clinical characteristics of inflammatory bowel disease (IBD) has not been fully clarified.MethodsThe levels of soluble IgA and IgG in sera and feces were detected by ELISA, and the percentage of IgA- and IgG-coated bacteria in feces was analyzed by flow cytometry. Crohn’s disease activity index (CDAI) and Simple Endoscopic Score for Crohn’s disease (SES-CD) for Crohn’s disease (CD) or Mayo score and ulcerative colitis endoscopic index of severity (UCEIS) for ulcerative colitis (UC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the disease activity.Results178 patients with CD, 75 patients with UC and 41 healthy donors were recruited in this study. We found that the concentrations of soluble IgA and IgG in feces of active IBD patients were significantly higher than those in healthy controls and that the levels of soluble IgA and IgG in feces from IBD patients were positively correlated with CRP, ESR, Mayo score, UCEIS, SES-CD, and CDAI, respectively. Moreover, we also observed that the percentage of IgA- and IgG-coated bacteria markedly increased in feces of IBD patients, especially in CD patients at the age of 17 to 40 years old, with terminal ileal lesions and perianal lesions, as well as from E2 UC patients, and was closely associated with disease activities.ConclusionsThe levels of soluble IgA and IgG and the percentage of IgA- and IgG-coated bacteria strikingly increase in feces of IBD patients and correlate with disease activity.

Pyrimorph is a novel fungicide from the carboxylic acid amide (CAA) family used to control plant-pathogenic oomycetes such as Phytophthora capsici. The proteomic response of P. capsici to pyrimorph was investigated using the iTRAQ technology to determine the target site of the fungicide and potential biomarker candidates of drug efficacy. A total of 1336 unique proteins were identified from the mycelium of wild-type P. capsici isolate (Hd3) and two pyrimorph-resistant mutants (R3-1 and R3-2) grown in the presence or absence of pyrimorph. Comparative analysis revealed that the three P. capsici isolates Hd3, R3-1, and R3-2 produced 163, 77, and 13 unique proteins, respectively, which exhibited altered levels of abundance in response to the pyrimorph treatment. Further investigations, using Cluster of Orthologous Groups of Proteins (COG) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified 35 proteins related to the mode of action of pyrimorph against P. capsici and 62 proteins involved in the stress response of P. capsici to pyrimorph. Many of the proteins with altered expression were associated with glucose and energy metabolism. Biochemical analysis using d-[U-(14) C]glucose verified the proteomics data, suggesting that the major mode of action of pyrimorph in P. capsici is the inhibition of cell wall biosynthesis. These results also illustrate that proteomics approaches are useful tools for determining the pathways targeted by novel fungicides as well as for evaluating the tolerance of plant pathogens to environmental challenges, such as the presence of fungicides.

Our results uncover a novel mechanism whereby anti-TNF therapy upregulates IL-22 production in CD patients through promoting Th22 cell differentiation and contributes to intestinal epithelial barrier repairs.

Phytophthora capsici causes significant loss to pepper production in China, and our objective was to investigate the population structure in Gansu province. Between 2007 and 2011, 279 isolates were collected from pepper at 24 locations. Isolates (or subsets) were assessed for simple sequence repeat (SSR) genotype, metalaxyl resistance, mating type, and physiological race using cultivars from the World Vegetable Center (AVRDC) and New Mexico recombinant inbred lines (NMRILs). The A1 and A2 mating types were recovered from nine locations and metalaxyl-resistant isolates from three locations. A total of 104 isolates tested on the AVRDC panel resolved five physiological races. None of 42 isolates tested on the NMRIL panel caused visible infection. SSR genotyping of 127 isolates revealed 59 unique genotypes, with 42 present as singletons and 17 having 2 to 13 isolates. Isolates with identical genotypes were recovered from multiple sites across multiple years and, in many cases, had different race types or metalaxyl sensitivities. Isolates clustered into three groups with each group having almost exclusively the A1 or A2 mating type. Overall it appears long-lived genetically diverse clonal lineages are dispersed across Gansu, outcrossing is rare, and functionally important variation exists within a clonal framework.