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Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies.

Background Recurrence and metastasis are the leading causes of tumour-related death in patients with oesophageal squamous cell carcinoma (ESCC). Tumour-infiltrating natural killer cells (NK cells) display powerful cytotoxicity to tumour cells and play a pivotal role in tumour therapy. However, the phenotype and functional regulation of NK cells in oesophageal squamous cell carcinoma (ESCC) remains largely unknown. Methods Single cell suspensions from blood and tissue samples were isolated by physical dissociation and filtering through a 70 μm cell strainer. Flow cytometry was applied to profile the activity and function of NK cells, and an antibody chip experiment was used to identify and quantitate cytokine levels. We studied IL-6 and IL-8 function in primary oesophageal squamous carcinoma and NK cell co-cultures in vitro and by a xenograft tumour model in vivo. Western blotting was used to quantitate STAT3 (signal transducer and activator of transcription 3) and p-STAT3 levels. Finally, we performed an IHC array to analyse IL-6/IL-8 (interleukin 6/interleukin 8) expression in 103 pairs of tumours and matched adjacent tissues of patients with ESCC to elucidate the correlation between IL-6 or IL-8 and clinical characteristics. Results The percentages of NK cells in both peripheral blood and tumour tissues from patients with ESCC were significantly increased in comparison with those in the controls and correlated with the clinical characteristics. Furthermore, the decrease in activating receptors and increase in inhibitory receptors on the surface of tumour-infiltrating NK cells was confirmed by flow cytometry. The level of granzyme B, the effector molecule of tumour-infiltrating NK cells, was also decreased. Mechanistically, primary ESCC cells activated the STAT3 signalling pathway on NK cells through IL-6 and IL-8 secretion, leading to the downregulation of activating receptors (NKp30 and NKG2D) on the surface of NK cells. An ex vivo study showed that blockade of STAT3 attenuated the IL-6/IL-8-mediated impairment of NK cell function. Moreover, the expression of IL-6 or IL-8 in tumour tissues was validated by immunohistochemistry to be positively correlated with tumour progression and poor survival, respectively. Conclusions Tumour cell-secreted IL-6 and IL-8 impair the activity and function of NK cells via STAT3 signalling and contribute to oesophageal squamous cell carcinoma malignancy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1310-0) contains supplementary material, which is available to authorized users.

Pyroptosis, an inflammatory form of programmed cell death, has been implicated in eliminating pathogenic infections. However, macrophage pyroptosis–related proteins from Mycobacterium tuberculosis (M.tb) have largely gone unexplored. Here, we identified a cell pyroptosis–inducing protein, Rv1579c, named EST12, secreted from the M.tb H37Rv region of difference 3. EST12 binds to the receptor for activated C kinase 1 (RACK1) in macrophages, and the EST12-RACK1 complex recruits the deubiquitinase UCHL5 to promote the K48-linked deubiquitination of NLRP3, subsequently leading to an NLRP3 inflammasome caspase-1/11–pyroptosis gasdermin D–interleukin-1β immune process. Analysis of the crystal structure of EST12 reveals that the amino acid Y80 acts as a critical binding site for RACK1. An EST12-deficient strain (H37RvΔEST12) displayed higher susceptibility to M.tb infection in vitro and in vivo. These results provide the first proof that RACK1 acts as an endogenous host sensor for pathogens and that EST12-RACK1–induced pyroptosis plays a pivotal role in M.tb-induced immunity.

Hypertension can lead to abnormal left atrial reservoir and conduit functions, and coexisting diabetes can further impair conduit function. 2DSTE-derived strain and strain rate imaging are sensitive methods for evaluating left atrial phasic function.