MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.

Phylogenetic reappraisal of Allium subgenus Cyathophora (Amaryllidaceae) and related taxa, with a proposal of two new sections.

The phylogeny of subgenus Cyathophora and representatives of its closely related taxa within Allium were reconstructed based on nrDNA ITS and two plastid fragments (trnL-F and rpl32-trnL). The constructed phylogenies indicated that subgenus Cyathophora was not monophyletic and to be split in three parts positioned in different clusters. Allium kingdonii was unequivocally placed within subgenus Amerallium and formed an immediate sister relationship with New World Amerallium clade, suggesting an unexpected intercontinental disjunct distribution. For another, Allium trifurcatum was firmly nested within subgenus Butomissa next to A. tuberosum and A. ramosum, but it is distinctly different morphologically from the latter by thinly leathery bulb tunics, uniovulate locule and obviously 3-cleft stigma. Based on the geographic features, morphological and molecular evidences, two new sections, Kingdonia X.J.He et D.Q.Huang for A. kingdonii and Trifurcatum X.J.He et D.Q.Huang for A. trifurcatum, were proposed. The remaining three species of subgenus Cyathophora formed a well-defined clade, and the phylogenetic relationships among them recovered were consistent with previous findings. In addition, A. weschniakowii and A. subtilissimum were proven to be a member of subgenera Rhizirideum sensu stricto (s. str.) and Cepa, respectively, rather than subgenera Cepa and Polyprason previously proposed. Section Rhizomatosa represented by A. caespitosum should be subsumed within section Caespitosoprason of subgenus Rhizirideum s. str.

Effect of molecular hydrogen treatment on Sepsis-Associated encephalopathy in mice based on gut microbiota.

INTRODUCTION: In our experiments, male wild-type mice were randomly divided into four groups: the sham, SAE, SAE + 2% hydrogen gas inhalation (H2 ), and SAE + hydrogen-rich water (HW) groups. The feces of the mice were collected for 16 S rDNA analysis 24 h after the models were established, and the serum and brain tissue of the mice were collected for nontargeted metabolomics analysis. AIM: Destruction of the intestinal microbiota is a risk factor for sepsis and subsequent organ dysfunction, and up to 70% of severely ill patients with sepsis exhibit varying degrees of sepsis-associated encephalopathy (SAE). The pathogenesis of SAE remains unclear. We aimed to explore the changes in gut microbiota in SAE and the regulatory mechanism of molecular hydrogen. RESULTS: Molecular hydrogen treatment significantly improved the functional outcome of SAE and downregulated inflammatory reactions in both the brain and the gut. In addition, molecular hydrogen treatment improved gut microbiota dysbiosis and partially amended metabolic disorder after SAE. CONCLUSIONS: Molecular hydrogen treatment promotes functional outcomes after SAE in mice, which may be attributable to increasing beneficial bacteria, repressing harmful bacteria, and metabolic disorder, and reducing inflammation.

Catalytic combustion of lean methane over different Co3O4 nanoparticle catalysts.

Three types of Co3O4 catalyst, namely Co3O4 nanoparticles (denoted as Co3O4-NPs, ∼12 nm in diameter), Co3O4 nanoparticles encapsulated in mesoporou s SiO2 (denoted as Co3O4@SiO2), and Co3O4 nanoparticles inside microporous SiO2 hollow sub-microspheres (denoted as Co3O4-in-SiO2), were explored to catalyze the combustion of lean methane. It was found that the methane conversion over the three catalysts has the order of Co3O4-NPs ≈ Co3O4@SiO2 > Co3O4-in-SiO2 due to the different catalyst structure. The comparison experiments at high temperatures indicate the Co3O4@SiO2 has a significantly improved anti-sintering performance. Combined with the TEM and BET measurements, the results prove that the presence of the mesoporous SiO2 layer can maintain the catalytical activity and significantly improve the anti-sintering performance of Co3O4@SiO2. In contrast, the microporous SiO2 layer reduces the catalytical activity of Co3O4-in-SiO2 possibly due to its less effective diffusion path of combustion product. Thus, the paper demonstrates the pore size of SiO2 layer and catalyst structure are both crucial for the catalytical activity and stability.

Molecular characterization of a cytokine-induced apoptosis inhibitor from Schistosoma japonicum.

Cytokine-induced apoptosis inhibitor (CIAP) is a novel antiapoptotic molecule, which is different to inhibitor of apoptosis protein or B-cell lymphoma 2. CIAP was originally identified as a molecule that conferred resistance to apoptosis induced by growth factor starvation. However, it remains to be undercharacterized in schistosomes. Here, we molecularly characterize a novel cytokine-induced apoptosis inhibitor from Schistosoma japonicum (SjCIAP). The transcription of the SjCIAP occurred at all of developmental stages investigated including eggs, cercariae, schistosomula, and adult schistosomes. Functional assay indicated that the SjCIAP could inhibit caspase activity in either human cell lines or schistosome lysates. Our preliminary results suggest that the SjCIAP may play important roles in parasitic living and development by regulating apoptosis, and drug target of SjCIAP might be a potential for schistosomiasis control.

Hydrogen-rich Saline Alleviated the Hyperpathia and Microglia Activation via Autophagy Mediated Inflammasome Inactivation in Neuropathic Pain Rats.

Neuropathic pain is a complication after a spinal nerve injury. The inflammasomes are now identified to be responsible for triggering inflammation in neuropathic pain. Autophagy participates in the process of neuropathic pain and can regulate the inflammasome activation in different diseases. Our previous research reported that hydrogen exerted a protective effect against neuropathic pain. Therefore, we focused on the mechanism and role of autophagy and inflammasome, by which hydrogen alleviated the hyperpathia induced by neuropathic pain. The results showed that neuropathic pain stimulated activation of inflammasome NLRP3 and autophagy pathway in the microglial cells of the spinal cord. The inhibition of NLRP3 inhibited the hyperpathia induced by spinal nerve litigation surgery. The absence of autophagy aggravated the inflammasome activity and hyperpathia. Hydrogen promoted autophagy related protein expression, inhibited the inflammasome NLRP3 pathway activation, and relieved the hyperpathia induced by neuropathic pain. Hydrogen treatment could alleviate hyperpathia by autophagy-mediated NLRP3 inactivation.

Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11 pathway.

Dexmedetomidine (Dex) has the neuroprotective effect on cerebral ischemia-reperfusion injury (CIRI). But the mechanism is not yet clear. In this study, we established a model of middle cerebral artery occlusion (MCAO) and treated primary cortical neurons with oxygen glucose deprivation (OGD), followed by Dex treatment. Neurological protection of Dex was then assessed by neurological deficit score, brain edema, TTC staining, TUNEL assay, Western blot analysis, immunohistochemistry, and RT-PCR. The results showed that Dex significantly reduced the neurological deficit score, brain edema and cerebral infarction area due to CIRI. After Dex treatment, the expression levels of ER stress-related apoptosis pathway proteins (GRP78, p-PERK, CHOP and Cleaved-caspase-3) were significantly decreased and the apoptosis of brain cells was also significantly reduced. Immunohistochemistry showed that expression and nuclear localization of CHOP decreased significantly after the application of Dex. The downstream apoptotic protein caspase-11 mediated by PERK-CHOP was also markedly inhibited by Dex. In conclusion, our results suggested that Dex reduced ER stress-induced apoptosis after CIRI. Its protective mechanism may be related to PERK-CHOP-Caspase-11 dependent signaling pathway.

Identification of in vivo protein phosphorylation sites in human pathogen Schistosoma japonicum by a phosphoproteomic approach.

Schistosome is the causative agent of human schistosomiasis and related animal disease. Reversible protein phosphorylation plays a key role in signaling processing that are vital for a cell and organism. However, it remains to be undercharacterized in schistosomes. In the present study, we characterized in vivo protein phosphorylation events in different developmental stages (schistosomula and adult worms) of Schistosoma japonicum by using microvolume immobilized metal-ion affinity chromatography (IMAC) pipette tips coupled to nanoLC-ESI-MS/MS. In total, 127 distinct phosphorylation sites were identified in 92 proteins in S. japonicum. A comparison of the phosphopeptides identified between the schistosomula and the adult worms revealed 30 phosphoproteins co-detected in both of the two worms. These proteins included several signal molecules and enzymes such as 14-3-3 protein, cysteine string protein, heat shock protein 90, epidermal growth factor receptor pathway substrate 8, proliferation-associated protein 2G4, peptidyl-prolyl isomerase G, phosphofructokinase and thymidylate kinase. Additionally, the phosphorylation sites were examined for phosphorylation specific motif and evolutionarily conservation. The study represents the first attempt to determine in vivo protein phosphorylation in S. japonicum by using a phosphoproteomic approach. The results by providing an inventory of phosphorylated proteins may facilitate to further understand the mechanisms involved in schistosome development and growth, and then may result in the development of novel vaccine candidates and drug targets for schistosomiasis control.