Genome-wide Integrative Analysis of Zika-Virus-Infected Neuronal Stem Cells Reveals Roles for MicroRNAs in Cell Cycle and Stemness.

Zika virus (ZIKV) infection is implicated in severe fetal developmental disorders, including microcephaly. MicroRNAs (miRNAs) post-transcriptionally regulate numerous processes associated with viral infection and neurodegeneration, but their contribution to ZIKV pathogenesis is unclear. We analyzed the mRNA and miRNA transcriptomes of human neuronal stem cells (hNSCs) during infection with ZIKV MR766 and Paraiba strains. Integration of the miRNA and mRNA expression data into regulatory interaction networks showed that ZIKV infection resulted in miRNA-mediated repression of genes regulating the cell cycle, stem cell maintenance, and neurogenesis. Bioinformatics analysis of Argonaute-bound RNAs in ZIKV-infected hNSCs identified a number of miRNAs with predicted involvement in microcephaly, including miR-124-3p, which dysregulates NSC maintenance through repression of the transferrin receptor (TFRC). Consistent with this, ZIKV infection upregulated miR-124-3p and downregulated TFRC mRNA in ZIKV-infected hNSCs and mouse brain tissue. These data provide insights into the roles of miRNAs in ZIKV pathogenesis, particularly the microcephaly phenotype

Zika virus infection reprograms global transcription of host cells to allow sustained infection.

Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-Barré syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection. The four cell types differed in their susceptibility to ZIKV infection, consistent with differences in their expression of viral response genes before infection. Clustering and network analyses of genes differentially expressed after ZIKV infection revealed changes related to the adaptive immune system, angiogenesis and host metabolic processes that are conducive to sustained viral production. Genes related to the adaptive immune response were downregulated in microglia cells, suggesting that ZIKV effectively evades the immune response after reaching the central nervous system. Like other viruses, ZIKV diverts host cell resources and reprograms the metabolic machinery to support RNA metabolism, ATP production and glycolysis. Consistent with these transcriptomic analyses, nucleoside metabolic inhibitors abrogated ZIKV replication in microglia cells

A Genome-Wide Survey on Basic Helix-Loop-Helix Transcription Factors in Giant Panda

The giant panda (Ailuropoda melanoleuca) is a critically endangered mammalian species. Studies on functions of regulatory proteins involved in developmental processes would facilitate understanding of specific behavior in giant panda. The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, mouse and human. Our present study identified 107 bHLH family members being encoded in giant panda genome. Phylogenetic analyses revealed that they belong to 44 bHLH families with 46, 25, 15, 4, 11 and 3 members in group A, B, C, D, E and F, respectively, while the remaining 3 members were assigned into “orphan”. Compared to mouse, the giant panda does not encode seven bHLH proteins namely Beta3a, Mesp2, Sclerax, S-Myc, Hes5 (or Hes6), EBF4 and Orphan 1. These results provide useful background information for future studies on structure and function of bHLH proteins in the regulation of giant panda development

Gastrodia elata powder capsule enhances anti-epileptic effect of carbamazepine by decreasing P-gp expression

Purpose: To investigate the influence of Gastrodia elata powder capsule (GC) or gastrodin (GTD) on the anti-epileptic effect of carbamazepine (CBZ) on penicillin (PG)-induced epilepsy in rats. Methods: A total 116 rats were used in this study. Rats in the control group (n = 8) were injected with normal saline (NS) in place PG. Epilepsy was induced in the remaining 108 rats on the first day via PG injection. The rats were then divided randomly into six groups (18 rats per group): PG group, CBZ group, CBZ + GC group, CBZ + GTD group, GC group, and GTD group, which were given (p.o.) NS, CBZ (100 mg/kg), CBZ (100 mg/kg.) + GC (350 mg/kg), CBZ (100 mg/kg) + GTD (100 mg/kg), GC (350 mg/kg), and GTD (100 mg/kg), respectively, once a day for 15 days. The behavioral characteristics of the rats were observed and used to assess the anti-epileptic effect of the test drugs. Real-time quantitative reverse transcription-PCR and Western blot assays were employed for the determination of the effect of CBZ, GC and GTD on the expression levels of P-gp. Results: CBZ significantly reduced the symptoms of epilepsy, while GC and GTD enhanced the antiepileptic effect of CBZ, and reversed the CBZ-induced increases in the protein expressions of mrd1a and P-gp (p < 0.05). Conclusion: GC reverses CBZ drug resistance, probably through downregulation of P-gp expression. This finding indicates that GC is a potential anti-epilepsy drug, but it merits further studies

Novel Tet(L) Efflux Pump Variants Conferring Resistance to Tigecycline and Eravacycline in Staphylococcus Spp.

Tigecycline is regarded as one of the few important last-resort antibiotics to treat complicated skin and intra-abdominal infections. Members of the genus Staphylococcus are zoonotic pathogens and pose a serious threat to public health. Tigecycline resistance in this species appears to be a rare phenomenon, and the mechanisms underlying tigecycline resistance have not been fully elucidated. Here, we report two novel variants of the tet(L) gene in Staphylococcus spp. from swine in China, designed as tet(L)F58L and tet(L)A117V. The tet(L)F58L was located within a 18,720 bp chromosomal multidrug resistance gene cluster flanked by two copies of IS257 in Staphylococcus cohnii 11-B-312, while the tet(L)A117V was located on a 6,292 bp plasmid in S. haemolyticus 11-B-93, which could be transferred to S. aureus by electrotransformation. Cloning of each of the two tet(L) variants into S. aureus RN4220 showed 16- or 8-fold increases in the minimal inhibition concentrations (MICs), which can fully confer the resistance to tigecycline (MICs from 0.125 to 2 mg/liter) and eravacycline (MICs from 0.125 to 1 or 2 mg/liter), but no increase in the MICs of omadacycline, compared with the MICs of the recipient strain S. aureus RN4220. In the in vivo murine sepsis and in the murine pneumonia models, an increase in CFU of S. aureus 29213_pT93 carrying the tet(L)A117V was seen despite tigecycline treatment. This observation suggests that the tet(L)A117V and its associated gene product compromise the efficacy of tigecycline treatment in vivo and may lead to clinical treatment failure. Our finding, that novel Tet(L) efflux pump variants which confer tigecycline and eravacycline resistance have been identified in Staphylococcus spp., requires urgent attention. IMPORTANCE Tigecycline and eravacycline are both important last-resort broad spectrum antimicrobial agents. The presence of novel Tet(L) efflux pump variants conferring the resistance to tigecycline and eravacycline in Staphylococcus spp. and its potential transmission to S. aureus will compromise the efficacy of tigecycline and eravacycline treatment for S. aureus associated infection in vivo and may lead to clinical treatment failure

Studies on the protective effect of total flavonoids from Cichorium glandulosum roots against carbon tetrachloride-induced liver fibrosis in rats

Purpose: To study the protective influence of total flavonoids from Cichorium glandulosum roots (TFCG) against carbon tetrachloride-mediated hepatic fibrosis in rats, and the probable mechanism of action involved.Methods: Rats with liver fibrosis were orally administered TFCG (50, 100 or 200 mg/kg) once a day for 13 weeks. Liver index and liver injury indices in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), lactate dehydrogenase (LDH), γ-glutamyl transpeptidase (γ-GT), hydroxyproline (HYP), albumin (ALB) and malondialdehyde (MDA) were determined using electronic balance or corresponding assay kits, as appropriate. Following staining with hematoxylin and eosin and Van Gieson, histopathological changes in liver tissues were examined by light microscopy. TGF-β/Smad pathway-related protein expressions in liver tissues, viz, transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3), Smad7, toll-like receptor 4 (TLR4) and α-smooth muscle actin (α-SMA) were determined using immunohistochemical techniques.Results: Exposure to TFCG significantly reversed abnormal serum levels of ALT, AST, AKP, LDH, γ- GT, HYP, ALB and MDA rats with liver fibrosis to normal levels, and also decreased their liver index values (p < 0.01). Moreover, TFCG improved histopathological changes in the liver tissues of fibrotic rats, and significantly reversed abnormal TGF-β1, Smad3, Smad7, TLR4 and α-SMA protein expressions in the liver tissues of fibrotic rats to normal levels (p < 0.05 or 0.01).Conclusion: These results indicate that TFCG exerts protective effect against liver fibrosis via a mechanism related to inactivation of TGF-β/Smad pathway. Thus, TFCG may find application in liver fibrosis therapy.Keywords: Cichorium glandulosum, Flavonoids, Liver, Fibrosis, TGF-β/Smad pathwa

A quasi real-time approach to investigating the damage and fracture process in plain concrete by X-ray tomography

In most concrete-related computer tomography (CT) experiments, detailed information on the damage and fracture process is obtained using nonreal-time approaches, with the CT method constantly regarded as a qualitative method. This study develops a quasi real-time method with the use of experimental instruments. The average CT number is used to analyse the damage and fracture process in concrete specimens and the theory that underlies concrete damage and fracture is improved. Various characteristics of the fracture form in different loading cases are investigated at the macro and micro levels. This study provides a convenient and fast method for qualitatively and quantitatively analysing concrete. First published online: 01 Jun 201

The Three Cement Slurry System Cementing Technology in SUBEI Oilfield JI2-41 Well

Abstract JI2-41 well is a directional development well located on Yunshuzhuang block structure in Dongtai Depression on SuBei basin of the SuBei oilfield. JI2-41 well is a normal development well which with the longest isolation section of SuBei oilfield. The design depth is 3481m,but actual depth is 3455m.The well is cemented with Ø139.7mm casing and the casing length is 3450m,required cement slurry return height more than 2500m.Because of this well reservoir section long,span large leads to there are many water layers between oil layers,borehole like a gourd,these factors which brought a lots problem to cementing. Author analysis the difficulty of cementing and advise to use three cement slurry system technology. It received cementing 93.1% with high quality when this technology applied on site operation. It solved the problem of cementing in SuBei oilfield