Systemic neutrophils are triggered by respiratory Bacillus Calmette- Guérin and mediate pulmonary mycobacterial clearance in synergy with the triggering receptor expressed on myeloid cells 1.

Tuberculosis remains a threat to public health. The only approved vaccine, Bacillus Calmette-Guérin (BCG), is administered intradermally and provides limited protection, and its effect on innate immunity via the respiratory route has not been fully elucidated. A mouse model with genetically depleted TREM1 and seven-color flow cytometry staining were used to characterize the comprehensive immune response induced by respiratory BCG, through evaluating organ bacterial loads, lung histopathology, and lung immunohistochemistry. During respiratory BCG infection, the murine lungs displayed effective bacterial clearance. Notably, marked differences in neutrophils were observed between thymus and bone marrow cells, characterized by a significant increase in the expression of the triggering receptor expressed on myeloid cells 1 (TREM1). Subsequently, upon depletion of TREM1, a reduction in pulmonary neutrophils was observed, which further exacerbated bacterial loads and resulted in worsened pathology following respiratory BCG infection. In summary, up-regulated expression of TREM1 in rapidly increasing circulating neutrophil by pulmonary BCG is required for an efficient host response to BCG infection, and suggests the important role of TREM1 in neutrophil-related pulmonary bacteria clearance and pathology.

Interleukin-17A Contributes to Bacterial Clearance in a Mouse Model of Streptococcal Toxic Shock-Like Syndrome.

Streptococcus suis (S. suis), an emerging zoonotic pathogen, can cause streptococcal toxic shock-like syndrome (STSLS) in humans with high mortality. STSLS is characterized by high bacterial burden, an inflammatory cytokine storm, multi-organ dysfunction, and ultimately acute host death. Although it has been found that a significantly high level of IL-17A was induced in an NLRP3-dependent manner during STSLS development, the role of IL-17A on S. suis STSLS remains to be elucidated. In this study, we found that the epidemic strain SC 19 caused a significantly higher level of IL-17A than the non-epidemic strain P1/7. In addition, higher bacterial burden was observed from SC 19-infected il17a-/- mice than il17a+/+ mice, although acute death, tissue injury and inflammatory cytokines storm were observed in both types of mice. Furthermore, compared with il17a+/+ mice, the level of neutrophils recruitment was lower in il17a-/- mice, and the levels of induced antimicrobial proteins, such as CRAMP, S100A8 and lipocalin-2, were also decreased in il17a-/- mice. In conclusion, this study demonstrated that IL-17A does not contribute to the severe inflammation, although it may play a minor role for bacterial clearance by inducing antimicrobial proteins and promoting neutrophil recruitment during STSLS.

Distinguishing brain inflammation from grade II glioma in population without contrast enhancement: a radiomics analysis based on conventional MRI.

PURPOSE: In populations without contrast enhancement, the imaging features of atypical brain parenchyma inflammations can mimic those of grade II gliomas. The aim of this study was to assess the value of the conventional MR-based radiomics signature in differentiating brain inflammation from grade II glioma. METHODS: Fifty-seven patients (39 patients with grade II glioma and 18 patients with inflammation) were divided into primary (n = 44) and validation cohorts (n = 13). Radiomics features were extracted from T1-weighted images (T1WI) and T2-weighted images (T2WI). Two-sample t-test and least absolute shrinkage and selection operator (LASSO) regression were adopted to select features and build radiomics signature models for discriminating inflammation from glioma. The predictive performance of the models was evaluated via area under the receiver operating characteristic curve (AUC) and compared with the radiologists' assessments. RESULTS: Based on the primary cohort, we developed T1WI, T2WI and combination (T1WI + T2WI) models for differentiating inflammation from glioma with 4, 8, and 5 radiomics features, respectively. Among these models, T2WI and combination models achieved better diagnostic efficacy, with AUC of 0.980, 0.988 in primary cohort and that of 0.950, 0.925 in validation cohort, respectively. The AUCs of radiologist 1's and 2's assessments were 0.661 and 0.722, respectively. CONCLUSION: The signature based on radiomics features helps to differentiate inflammation from grade II glioma and improved performance compared with experienced radiologists, which could potentially be useful in clinical practice.

Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection.

BACKGROUND: Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism. RESULTS: Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect. CONCLUSIONS: These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.

[Accuracy evaluation of multi-satellite precipitation products over Circum-Bohai-Sea Region.] / 多卫星降水产品在环渤海地区的精度评价.

Precipitation is a key variable of the global energy and water cycle. The accuracy of precipitation data is essential for monitoring and forecasting flood and drought, as well as water resources management. Based on daily precipitation data of 55 meteorological stations over Circum-Bohai-Sea region during 1998-2014, the accuracy was evaluated and compared among 3 satellite-based precipitation products, i.e., TRMM 3B42 V7, CMORPH, and PERSIANN from daily to monthly scale. Their errors were quantified for different seasons. Results showed that generally, TRMM 3B42 V7 had the best performance while PERSIANN had the largest error. However, CMORPH had the highest detection rate of rainfall events. The rainfall was slightly overestimated by 3B42 V7 but underestimated by CMORPH and PERSIANN. Seasonally, the skill score in summer was higher than that in other seasons, and the capturing capability was much lower in winter. Meanwhile, the correlation coefficient and root mean square error varied with seasons. The performance of 3 satellite-based precipitation products increased from the daily to monthly scale. Larger errors still existed in the daily rainfall estimates, and especially the rainstorm was seriously underestimated. This study provided a basis for the use of satellite precipitation products in precipitation estimation and its application in climate and hydrological simulation over Circum-Bohai-Sea region.

[Research on the characteristics of Ulva prolifera in Shandong Peninsula during 2008-2012 based on MODIS data].

In the present study, the MODIS data were used to monitor the situation of Ulva prolifera in the Shandong Peninsula waters during the period of 2008-2012. Those studies mainly calculate the area of NDVI, and get the information of the time, area , scope , floating path of Ulva prolifera by using threshold segmentation method. The feasibility of monitoring Ulva prolifera information based on MODIS data and the macroscopic regularity of the outburst of Ulva prolifera was elementally studied. The results showed that Ulva prolifera first generated in the middle of May or early June, the time, area, scope of Ulva prolifera reached a maximum, but the relative crowding density was earlier or later when Ulva prolifera developed into a outburst. Finally, Ulva prolifera died away after existing for 71 days in the late July or the early August. Wholly, the floating path moved to the northwest from off the coast to offshore. Based on those aspects above, the outburst of Ulva prolifera in 2008 and 2009 was more serious than others.

Molecular mechanism by which surface antigen HP0197 mediates host cell attachment in the pathogenic bacteria Streptococcus suis.

Streptococcus suis, one of the most important and prevalent pathogens in swine, presents a major challenge to global public health. HP0197 is an S. suis surface antigen that was previously identified by immunoproteomics and can bind to the host cell surface. Here, we investigated the interaction between HP0197 and the host cell surface glycosaminoglycans (GAGs) using indirect immunofluorescence and cell adhesion inhibition assays. In addition, we determined that a novel 18-kDa domain in the N-terminal region of HP0197 functions as the GAG-binding domain. We then solved the three-dimensional structures of the N-terminal 18-kDa and C-terminal G5 domains using x-ray crystallography. Based on this structural information, the GAG-binding sites in HP0197 were predicted and subsequently verified using site-directed mutagenesis and indirect immunofluorescence. The results indicate that the positively charged residues on the exposed surface of the 18-kDa domain, which are primarily lysines, likely play a critical role in the HP0197-heparin interaction that mediates bacterium-host cell adhesion. Understanding this molecular mechanism may provide a basis for the development of effective drugs and therapeutic strategies for treating streptococcal infections.

Evolutionary characterization of influenza virus A/duck/Hubei/W1/2004 (H9N2) isolated from central China.

Full-length eight gene segments of avian influenza virus A/duck/Hubei/W1/2004(H9N2) (Dk/Hub/W1/04) were amplified by RT-PCR and completely sequenced. Phylogenetic analysis revealed that Dk/Hub/W1/04 was derived from A/Duck/HongKong/Y280/97, not displaying direct evolutional relationship with A/Quail/HongKong/G1/97 or Hubei H5N1 viruses. Meanwhile, Dk/Hub/W1/04 was found highly related to recent three chicken isolates. The connecting peptide of HA and the deletion in NA stalk were consistent with three chicken isolates, and the number of potential glycosylation site on the HA and NA also was similar or identical to the three chicken isolates. These findings suggested that Dk/Hub/W1/04 is likely to transmit back to ducks from chickens.

[Preparation and partial characterization of monoclonal antibodies specific for nuclear protein of avian influenza virus].

AIM: To prepare the monoclonal antibodies (mAbs) specific for nuclear protein (NP) of avian influenza virus (AIV) and identify their biological properties. METHODS: BALB/c mice were immunized with AIV (formaldehyde-inactivated AIV H9N2, Triton X-100-lysed H9N2 and AIV NP expressed in E.coli, respectively). Hybridoma cell lines secreting anti-AIV NP mAbs were developed through cell fusion, screening and cloning. The mAb's titer was determined by indirect ELISA. Specificity of mAbs was identified by cross-reaction test and indirect immuno-fluorescence assay (IFA). RESULTS: 6 hybridoma cell lines secreting anti-AIV NP mAbs were obtained, designated 4F4, 1C3, 1G11, 1C2, 1D10 and 2F7. ELISA detection showed that the titers of two mAbs (1G11 and 1D10) out of 6 mAbs were the highest (2(-13) and 2(-14), respectively) and their specificity was also better than that of the others, confirmed by cross-reaction test and IFA. CONCLUSION: In this study 6 mAbs against AIV NP were obtained. The mAbs 1G11 and 1D10 perform the best in titer and specificity. This work paves the way for AIV study and development of method for rapid detection of AIV.