Background Cryptosporidiosis is a major cause of gastrointestinal diseases in humans and other vertebrates. Previous analyses of invasion-related proteins revealed that Cryptosporidium parvum , Cryptosporidium hominis , and Cryptosporidium ubiquitum mainly differed in copy numbers of secreted MEDLE proteins and insulinase-like proteases and sequences of mucin-type glycoproteins. Recently, Cryptosporidium chipmunk genotype I was identified as a novel zoonotic pathogen in humans. In this study, we sequenced its genome and conducted a comparative genomic analysis. Results The genome of Cryptosporidium chipmunk genotype I has gene content and organization similar to C. parvum and other intestinal Cryptosporidium species sequenced to date. A total of 3783 putative protein-encoding genes were identified in the genome, 3525 of which are shared by Cryptosporidium chipmunk genotype I and three major human-pathogenic Cryptosporidium species, C. parvum , C. hominis , and Cryptosporidium meleagridis . The metabolic pathways are almost identical among these four Cryptosporidium species. Compared with C. parvum , a major reduction in gene content in Cryptosporidium chipmunk genotype I is in the number of telomeric genes encoding MEDLE proteins (two instead of six) and insulinase-like proteases (one instead of two). Highly polymorphic genes between the two species are mostly subtelomeric ones encoding secretory proteins, most of which have higher dN/dS ratios and half are members of multiple gene families. In particular, two subtelomeric ABC transporters are under strong positive selection. Conclusions Cryptosporidium chipmunk genotype I possesses genome organization, gene content, metabolic pathways and invasion-related proteins similar to the common human-pathogenic Cryptosporidium species, reaffirming its human-pathogenic nature. The loss of some subtelomeric genes encoding insulinase-like proteases and secreted MEDLE proteins and high sequence divergence in secreted pathogenesis determinants could contribute to the biological differences among human-pathogenic Cryptosporidium species. Electronic supplementary material The online version of this article (10.1186/s12864-019-5788-9) contains supplementary material, which is available to authorized users.

BackgroundCyclospora cayetanensis is an apicomplexan that causes diarrhea in humans. The investigation of foodborne outbreaks of cyclosporiasis has been hampered by a lack of genetic data and poor understanding of pathogen biology. In this study we sequenced the genome of C. cayetanensis and inferred its metabolism and invasion components based on comparative genomic analysis.ResultsThe genome organization, metabolic capabilities and potential invasion mechanism of C. cayetanensis are very similar to those of Eimeria tenella. Propanoyl-CoA degradation, GPI anchor biosynthesis, and N-glycosylation are some apparent metabolic differences between C. cayetanensis and E. tenella. Unlike Eimeria spp., there are no active LTR-retrotransposons identified in C. cayetanensis. The similar repertoire of host cell invasion-related proteins possessed by all coccidia suggests that C. cayetanensis has an invasion process similar to the one in T. gondii and E. tenella. However, the significant reduction in the number of identifiable rhoptry protein kinases, phosphatases and serine protease inhibitors indicates that monoxenous coccidia, especially C. cayetanensis, have limited capabilities or use a different system to regulate host cell nuclear activities. C. cayetanensis does not possess any cluster of genes encoding the TA4-type SAG surface antigens seen in E. tenella, and may use a different family of surface antigens in initial host cell interactions.ConclusionsOur findings indicate that C. cayetanensis possesses coccidia-like metabolism and invasion components but unique surface antigens. Amino acid metabolism and post-translation modifications of proteins are some major differences between C. cayetanensis and other apicomplexans. The whole genome sequence data of C. cayetanensis improve our understanding of the biology and evolution of this major foodborne pathogen and facilitate the development of intervention measures and advanced diagnostic tools.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2632-3) contains supplementary material, which is available to authorized users.

Purpose Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations. Patients and Methods A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan–Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort. Results All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively ( p =0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% ( p <0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045–1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351–3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014–3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177–3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001–1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081–1.232, p<0.001) were independent predictors of mortality following amputation. Conclusion Postoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.

The three common intestinal Cryptosporidium species in cattle differ significantly in host range, pathogenicity and public health significance. While Cryptosporidium parvum is pathogenic in pre-weaned calves and has a broad host range, C. bovis and C. ryanae are largely non-pathogenic and bovine-specific species in post-weaned calves. Thus far, only the genome of C. parvum has been sequenced. To improve our understanding of the genetic determinants of biological differences among Cryptosporidium spcies, we sequenced the genomes of C. bovis and C. ryanae and conducted a comparative genomics analysis. The genome of C. bovis has a gene content and organization more similar to C. ryanae than to other Cryptosporidium species sequenced to date; the level of similarity in amino acid and nucleotide sequences between the two species is 75.2 and 69.4 %, respectively. A total of 3723 and 3711 putative protein-encoding genes were identified in the genomes of C. bovis and C. ryanae, respectively, which are fewer than the 3981 in C. parvum. Metabolism is similar among the three species, although energy production pathways are further reduced in C. bovis and C. ryanae. Compared with C. parvum, C. bovis and C. ryanae have lost 14 genes encoding mucin-type glycoproteins and three for insulinase-like proteases. Other gene gains and losses in the two bovine-specific and non-pathogenic species also involve the secretory pathogenesis determinants (SPDs); they have lost all genes encoding MEDLE, FLGN and SKSR proteins, and two of the three genes for NFDQ proteins, but have more genes encoding secreted WYLE proteins, secreted leucine-rich proteins and GPI-anchored adhesin PGA18. The only major difference between C. bovis and C. ryanae is in nucleotide metabolism. In addition, half of the highly divergent genes between C. bovis and C. ryanae encode secreted or membrane-bound proteins. Therefore, C. bovis and C. ryanae have gene organization and metabolic pathways similar to C. parvum, but have lost some invasion-associated mucin glycoproteins, insulinase-like proteases, MEDLE secretory proteins and other SPDs. The multiple gene families under positive selection, such as helicase-associated domains, AMP-binding domains, protein kinases, mucins, insulinases and TRAPs could contribute to differences in host specificity and pathogenicity between C. parvum and C. bovis. Biological studies should be conducted to assess the contribution of these copy number variations to the narrow host range and reduced pathogenicity of C. bovis and C. ryanae.

BackgroundOxidative stress is associated with outcomes of chronic lung disease. The oxidative stress-related exposures of diet and lifestyle can be evaluated by the oxidative balance score (OBS), and higher OBS scores indicate more significant antioxidant exposures. But the relationship between OBS and lung health is unknown.PurposeThe aim of this study was to explore the association between OBS and lung health (respiratory symptoms, chronic lung disease, and lung function).MethodsA series of models, including weighted linear models, weighted logistic regression, and weighted multinomial logistic regression, were performed to assess the associations of OBS with respiratory symptoms, chronic lung disease, and lung function. The models adjusted by age, race/ethnicity, gender, educational background, poverty-to-income ratio, and dietary energy were also performed.ResultsCross-sectional data of 5,214 participants from the National Health and Nutrition Examination Survey for the years 2007–2012 were analyzed. For every one-unit increase in OBS, the odds of wheezing/chronic bronchitis decreased by 6%. Increased OBS was associated with higher percent-predicted forced expiratory volume in one second (FEV1) (adjusted mean difference (MD), 0.21%; 95% CI: 0.10–0.32) and percent-predicted forced vital capacity (FVC) (adjusted MD, 0.15%; 95% CI: 0.07–0.24). A significantly lower risk of wheezing/chronic bronchitis was found in participants in the second/third/fourth OBS quartile compared to those in the first OBS quartile (all P for trend &lt; 0.05). Moreover, higher percent-predicted FEV1 and FVC were also found in the third quartile and fourth quartile (all P for trend &lt; 0.05). Furthermore, both dietary and lifestyle components were tightly related to pulmonary outcomes. Many associations were maintained after stratified by sex or after sensitivity analyses.ConclusionOxidative balance score was negatively correlated with the diagnosis of chronic bronchitis/wheezing/restrictive spirometry pattern and positively correlated with percent-predicted FVC and FEV1. It seems that the higher the OBS score, the better the pulmonary outcomes. The findings highlight the importance of adherence to an antioxidant diet and lifestyle and that it contributes to lung health.

Background: Sarcopenia, or skeletal muscle depletion, was common in the elderly and often led to a poor prognosis of diseases. The area of the psoas muscle in abdominal computed tomography (CT) is the most common used for diagnosing sarcopenia. However, patients with pneumonia routinely only undergo chest CT.Objectives: This study aimed to determine whether paraspinal muscle area (PMA) obtained by chest CT can predict death for community-acquired pneumonia (SCAP) patients entering intensive care unit (ICU). Methods: This study enrolled 208 SCAP patients admitted to ICU after undergoing chest CT. PMA, paraspinal muscle radiodensity (PMD), and lean paraspinal muscle area (LPMA) were calculated on chest CT images. The main outcome was mortality during hospitalization. Logistic regression, receiver operating characteristic (ROC) curve, and Kaplan-Meier curves were used to evaluate forecasting effectiveness. Results: The primary outcome occurred in 76 (36.53%) patients. In multivariate logistic regression, PMA, lactic dehydrogenase (LDH), invasive mechanical ventilation (IMV), red blood cell (RBC) and age 65 years were independent risk factors predicting death during hospitalization (adjusted Odds Ratio [OR]: 0.886, 1.002, 3.178, 0.612 and 2.003, respectively). The area under curve (AUC) of PMA to predict death was 0.720 (P< 0.001). During hospitalization, the median survival time of high-PMA (51.00 days) and low-PMA groups (20.00 days) was statistically significant (P< 0.001). Conclusion: Lower PMA was associated with an increased risk of death for SCAP patients admitted to the ICU. In other words, PMA may help early identify adverse prognosis of SCAP patients admitted to ICU.

Background. Lung adenocarcinoma (LUAD) is one of the most life-threatening malignancies. The crucial role of bone morphogenetic protein (BMP)/BMP receptors reveals the significance of exploring BMP protein-related prognostic predictors in LUAD. Methods. The mRNA expression of BMPs/BMP receptors was investigated in LUAD and normal lung tissues. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and the prognostic values were assessed by Kaplan-Meier Plotter. Univariate and multivariate Cox regression analyses were executed to ascertain the correlation between overall survival (OS) and the mRNA expression of BMPs/BMP receptors. The receiver operating characteristic (ROC) curves were implemented to evaluate the predictive power of the prognostic model. Then, the prognostic model was validated in the GEO cohort. Furthermore, a nomogram comprising the prognostic model was established. Results. The mRNA expression of BMP2/5/6/R2, ACVRL1, and TGFBR2/3 was lower in LUAD tissues than in normal lung tissues. High expression of BMP2/4/5/R1A/R2, ACVR1/2A/L1, and TGFBR1/3 was associated with better OS, while BMP7 and ACVR1C/2B were associated with poorer OS. Three genes (BMP5, BMP7, and ACVR2A) were screened by univariate and multivariate Cox regression analyses to develop the prognostic model in TCGA. Significantly better survival was observed in LUAD patients with a low-risk score than those with a high-risk score. The ROC curves confirmed the good performance of the prognostic model, then, the prognostic model was validated in the GSE31210 dataset. A nomogram was constructed (AUCs>0.7). And hub genes were further evaluated, including gene set enrichment analysis and immune cell infiltration. Conclusions. BMP5, BMP7, and ACVR2A are potential therapeutic targets in LUAD. The three-gene prognostic model and the nomogram are reliable tools for predicting the OS of LUAD patients.

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