1,1-Dimethyl­hydrazin-1-ium picrate

In the title compound, C2H9N2 +·C6H2N3O7 −, the dihedral angles between the mean planes of the three nitro groups and the benzene ring are 63.5 (3), 10.5 (2) and 10.4 (2)°. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds into a two-dimensional network parallel to (001)

Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer

PURPOSE: MicroRNAs (miRNAs) play an essential role in breast malignant tumor development and progression. The development of clinically validated biomarkers for primary breast cancer (BC) has remained an insurmountable task despite other advances in the field of cancer molecular biology. The objective of this study is to investigate the differential expression of miRNAs and the potential of circulating microRNAs as novel primary breast cancer biomarkers. METHODS: Our analyses were performed on 48 tissue and 100 serum samples of patients with primary BC and a set of 20 control samples of healthy women, respectively. The relative expression of ten candidate miRNAs (miR-106b, miR-125b, miR-17, miR-185, miR-21, miR-558, miR-625, miR-665, miR-92a, and miR-93) from the results of four bioinformatics approaches and literature curation was measured by real-time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The level of miR-92a was significantly lower, while miR-21 was higher, as previous reports, in tissue and serum samples of BC than that of healthy controls (p < 0.001). Logistic regression and receiver operating characteristic curve analyses revealed the significant and independent value (p < 0.001) of the miR-92a and miR-21 expression quantification in serums. Moreover, the comparison with the clinicopathologic data of the BC patients showed that decreased levels of miR-92a and increased levels of miR-21 were associated with tumor size and a positive lymph node status (p < 0.001). CONCLUSIONS: These findings suggest that many miRNAs expressions are altered in BC, whose expression profiling may provide a useful clue for the pathophysiological research. Circulating miR-92a has potential use as novel breast cancer biomarker, which is comparable to miR-21

African swine fever virus pA104R protein acts as a suppressor of type I interferon signaling

This study evaluates the role of the late viral protein, pA104R, in African swine fever virus immunosuppression. ASFV-encoded pA104R is a putative histone-like protein that is highly conserved throughout different virulent and non-virulent isolates. Previous studies have demonstrated that pA104R plays a vital role in the ASFV replication cycle and is a potential target for antiviral therapy. Here, we demonstrated that pA104R is a potent antagonist of type I interferon signaling. IFN-stimulated response element activity and subsequent transcription of co-transfected and endogenous interferon-stimulated genes were attenuated by pA104R treatment in HEK-293 T cells. Immunoprecipitation assay and reciprocal pull-down showed that pA104R does not interact directly with STAT1, STAT2, or IRF9. However, pA104R could inhibit IFN signaling by attenuating STAT1 phosphorylation, and we identified the critical amino acid residues (R/H69,72 and K/R92,94,97) involved through the targeted mutation functional assays. Although pA104R is a histone-like protein localized to the nucleus, it did not inhibit IFN signaling through its DNA-binding capacity. In addition, activation of the ISRE promoter by IRF9-Stat2(TA), a STAT1-independent pathway, was inhibited by pA104R. Further results revealed that both the transcriptional activation and recruitment of transcriptional stimulators by interferon-stimulated gene factor 3 were not impaired. Although we failed to determine a mechanism for pA104R-mediated IFN signaling inhibition other than attenuating the phosphorylation of STAT1, these results might imply a possible involvement of epigenetic modification by ASFV pA104R. Taken together, these findings support that pA104R is an antagonist of type I interferon signaling, which may interfere with multiple signaling pathways

Attenuation of Mycoplasma hyopneumoniae Strain ES-2 and Comparative Genomic Analysis of ES-2 and Its Attenuated Form ES-2L

Mycoplasma hyopneumoniae causes swine respiratory disease worldwide. Due to the difficulty of isolating and cultivating M. hyopneumoniae, very few attenuated strains have been successfully isolated, which hampers the development of attenuated vaccines. In order to produce an attenuated M. hyopneumoniae strain, we used the highly virulent M. hyopneumoniae strain ES-2, which was serially passaged in vitro 200 times to produce the attenuated strain ES-2L, and its virulence was evidenced to be low in an animal experiment. In order to elucidate the mechanisms underlying virulence attenuation, we performed whole-genome sequencing of both strains and conducted comparative genomic analyses of strain ES-2 and its attenuated form ES-2L. Strain ES-2L showed three large fragment deletion regions including a total of 18 deleted genes, compared with strain ES-2. Analysis of single-nucleotide polymorphisms (SNPs) and indels indicated that 22 dels were located in 19 predicted coding sequences. In addition to these indels, 348 single-nucleotide variations (SNVs) were identified between strains ES-2L and ES-2. These SNVs mapped to 99 genes where they appeared to induce amino acid substitutions and translation stops. The deleted genes and SNVs may be associated with decreased virulence of strain ES-2L. Our work provides a foundation for further examining virulence factors of M. hyopneumoniae and for the development of attenuated vaccines

Isolation of Mycobacterium tuberculosis complex (MTBC) from dairy cows in China

Eleven thousand five hundred and eighty non-blood samples from dairy cows were subjected to mycobacterium culture and genotyping. As a result, a total of 142 isolates of Mycobacterium tuberculosis complex (MBTC) were identified. Among them, 65 were Mycobacterium tuberculosis, while 77 Mycobacterium bovis. The genotype of M. tuberculosis strains was mainly Beijing family. In addition, the isolation rates of MTBC were 33.89% for lung lymph nodes, 2.81% for nasal swabs, and 3.95% for pharyngeal swabs from cattle positive to tuberculin skin test, respectively. This evidence implied that M. tuberculosis infection in cattle is a new risk to public health and should be paid more attention.Key words: Mycobacterium tuberculosis complex, cows, tuberculosis, zoonosis

Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

AbstractThe high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection

Transactivated Epidermal Growth Factor Receptor Recruitment of α-actinin-4 From F-actin Contributes to Invasion of Brain Microvascular Endothelial Cells by Meningitic Escherichia coli

Bacterial penetration of the blood-brain barrier requires its successful invasion of brain microvascular endothelial cells (BMECs), and host actin cytoskeleton rearrangement in these cells is a key prerequisite for this process. We have reported previously that meningitic Escherichia coli can induce the activation of host's epidermal growth factor receptor (EGFR) to facilitate its invasion of BMECs. However, it is unknown how EGFR specifically functions during this invasion process. Here, we identified an important EGFR-interacting protein, α-actinin-4 (ACTN4), which is involved in maintaining and regulating the actin cytoskeleton. We observed that transactivated-EGFR competitively recruited ACTN4 from intracellular F-actin fibers to disrupt the cytoskeleton, thus facilitating bacterial invasion of BMECs. Strikingly, this mechanism operated not only for meningitic E. coli, but also for infections with Streptococcus suis, a Gram-positive meningitis-causing bacterial pathogen, thus revealing a common mechanism hijacked by these meningitic pathogens where EGFR competitively recruits ACTN4. Ever rising levels of antibiotic-resistant bacteria and the emergence of their extended-spectrum antimicrobial-resistant counterparts remind us that EGFR could act as an alternative non-antibiotic target to better prevent and control bacterial meningitis