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It is widely accepted that chronic hepatitis B virus (HBV) infection is the result of an ineffective antiviral immune response against HBV infection. Our previous study found that the hepatitis B surface Ag (HBsAg) was related to decreased cytokine production induced by the TLR2 ligand (Pam3csk4) in PBMCs from chronic hepatitis B patients. In this study, we further explored the mechanism involved in the inhibitory effect of HBsAg on the TLR2 signaling pathway. The results showed that both Pam3csk4-triggered IL-12p40 mRNA expression and IL-12 production in PMA-differentiated THP-1 macrophage were inhibited by HBsAg in a dose-dependent manner, but the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α was not influenced. The Pam3csk4-induced activation of NF-κB and MAPK signaling were further examined. The phosphorylation of JNK-1/2 and c-Jun was impaired in the presence of HBsAg, whereas the degradation of IκB-α, the nuclear translocation of p65, and the phosphorylation of p38 and ERK-1/2 were not affected. Moreover, the inhibition of JNK phosphorylation and IL-12 production in response to Pam3csk was observed in HBsAg-treated monocytes/macrophages (M/MΦs) from the healthy donors and the PBMCs and CD14-positive M/MΦs from chronic hepatitis B patients. Taken together, these results demonstrate that HBsAg selectively inhibits Pam3csk4- stimulated IL-12 production in M/MΦs by blocking the JNK–MAPK pathway and provide a mechanism by which HBV evades immunity and maintains its persistence.

BackgroundEggplant (Solanum melongena L.) and turkey berry (S. torvum Sw.), a wild ally of eggplant with promising multi-disease resistance traits, are of great economic, medicinal and genetic importance, but genomic resources for these species are lacking. In the present study, we sequenced the transcriptomes of eggplant and turkey berry to accelerate research on these two non-model species.ResultsWe built comprehensive, high-quality de novo transcriptome assemblies of the two Leptostemonum clade Solanum species from short-read RNA-Sequencing data. We obtained 34,174 unigenes for eggplant and 38,185 unigenes for turkey berry. Functional annotations based on sequence similarity to known plant datasets revealed a distribution of functional categories for both species very similar to that of tomato. Comparison of eggplant, turkey berry and another 11 plant proteomes resulted in 276 high-confidence single-copy orthologous groups, reasonable phylogenetic tree inferences and reliable divergence time estimations. From these data, it appears that eggplant and its wild Leptostemonum clade relative turkey berry split from each other in the late Miocene, ~6.66 million years ago, and that Leptostemonum split from the Potatoe clade in the middle Miocene, ~15.75 million years ago. Furthermore, 621 and 815 plant resistance genes were identified in eggplant and turkey berry respectively, indicating the variation of disease resistance genes between them.ConclusionsThis study provides a comprehensive transcriptome resource for two Leptostemonum clade Solanum species and insight into their evolutionary history and biological characteristics. These resources establish a foundation for further investigations of eggplant biology and for agricultural improvement of this important vegetable. More generally, we show that RNA-Seq is a fast, reliable and cost-effective method for assessing genome evolution in non-model species.Electronic supplementary materialThe online version of this article (doi: 10.1186/1471-2164-15-412) contains supplementary material, which is available to authorized users.

The human tissue-type plasminogen activator (tPA) is a key kinase of fibrinolysis that plays an important role in dissolving fibrin clots to promote thrombolysis. The recombinant human plasminogen activator (rhPA) has more thrombolytic advantages than the wild type tPA. To increase the half-life and thrombolytic activity of tPA, a mutant containing only the essential K2 fibrin-binding and P activating plasminogen domains of the wild type tPA was cloned. This fragment was then inserted into goat β-casein regulatory sequences. Then, a mammary gland-specific expression vector, PCL25/rhPA, was constructed, and the transgenic rabbits were generated. In this study, 18 live transgenic founders (12♀, 6♂) were generated using pronuclear microinjection. Six transgenic rabbits were obtained, and the expression levels of rhPA in the milk had a range of 15.2-630 µg/ml. A fibrin agarose plate assay of rhPA showed that it had strong thrombolytic bioactivity in vitro, and the highest specific activity was >360 (360 times more than that of alteplase). The results indicated that the rhPA containing only the K2 and P domains is efficiently expressed with higher thrombolytic bioactivity in the milk of transgenic rabbits. Our study also demonstrated a new method for the large-scale production of clinically relevant recombinant pharmaceutical proteins in the mammary glands of transgenic rabbits.

Despite steady progress in elimination of measles virus globally, measles infection still causes 500,000 annual deaths, mostly in developing countries where endemic measles strains still circulate. Many adults are infected every year in China, with symptoms more severe than those observed in children. In this study, we have used blood samples from adult measles patients in Shanghai and age-matched healthy controls to gain an understanding of the immune status of adult measles patients. IFN-α mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-γ were elevated in patient blood. A similar cytokine profile was observed at early times when cultured PBMC were infected with a clinical isolate of measles virus. In contrast to previous studies in pediatric patients, we did not find a reduction in total CD4+ and CD8+ T cells in patient PBMC. Interestingly, we found that CD4+CD25+CD127low regulatory T cells were significantly increased in patient PBMC compared with controls. Using intracellular cytokine staining we also show that the measles virus induces IL-10-producing CD14+ and CD4+CD25+ cells in PBMC. Our results show that adult measles patients in the acute phase of the disease have a mixed Th1/Th2 type response, accompanied with severe immunosuppression of both innate and adaptive responses including suppression of type I IFN. Both regulatory T cells and plasma IL-10 may contribute to the immunosuppression.

BackgroundLow temperature is an important abiotic stress in plant growth and development, especially for thermophilic plants. Eggplants are thermophilic vegetables, although the molecular mechanism of their response to cold stress remains to be elucidated. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play an essential role during plant development and stress responses. Although the role of many plant miRNAs in facilitating chilling tolerance has been verified, little is known about the mechanisms of eggplant chilling tolerance.ResultsHere, we used high-throughput sequencing to extract the miRNA and target genes expression profiles of Solanum aculeatissimum (S. aculeatissimum) under low temperature stress at different time periods(0 h, 2 h, 6 h, 12 h, 24 h). Differentially regulated miRNAs and their target genes were analyzed by comparing the small RNA (sRNA) and miRBase 20.0 databases using BLAST or BOWTIE, respectively. Fifty-six down-regulated miRNAs and 28 up-regulated miRNAs corresponding to 220 up-regulated mRNAs and 94 down-regulated mRNAs, respectively, were identified in S. aculeatissimum. Nine significant differentially expressed miRNAs and twelve mRNAs were identified by quantitative Real-time PCR and association analysis, and analyzed for their GO function enrichment and KEGG pathway association.ConclusionsIn summary, numerous conserved and novel miRNAs involved in the chilling response were identified using high-throughput sequencing, which provides a theoretical basis for the further study of low temperature stress-related miRNAs and the regulation of cold-tolerance mechanisms of eggplant at the miRNA level.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4341-y) contains supplementary material, which is available to authorized users.

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