Sharp turns and gyrotaxis modulate surface accumulation of microorganisms.

The accumulation of swimming microorganisms at surfaces is an essential feature of various physical, chemical, and biological processes in confined spaces. To date, this accumulation is mainly assumed to depend on the change of swimming speed and angular velocity caused by cell-wall contact and hydrodynamic interaction. Here, we measured the swimming trajectories of Heterosigma akashiwo (a biflagellate marine alga) near vertical and horizontal rigid boundaries. We observed that the probability of sharp turns is greatly increased near a vertical wall, resulting in significant changes in the distributions of average swimming speed, angular velocity, and rotational diffusivity near the wall (a quantity that has not previously been investigated) as functions of both distance from the wall and swimming orientation. These cannot be satisfactorily explained by standard hydrodynamic models. Detailed examination of an individual cell trajectory shows that wall contact by the leading flagellum triggers complex changes in the behavior of both flagella that cannot be incorporated in a mechanistic model. Our individual-based model for predicting cell concentration using the measured distributions of swimming speed, angular velocity, and rotational diffusivity agrees well with the experiment. The experiments and model are repeated for a cell suspension in a vertical plane, bounded above by a horizontal wall. The cell accumulation beneath the wall, expected from gyrotaxis, is considerably amplified by cell-wall interaction. These findings may shed light on the prediction and control of cell distribution mediated by gyrotaxis and cell-wall contact

Neferine ameliorates hypertensive vascular remodeling modulating multiple signaling pathways in spontaneously hypertensive rats

Background: Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms. Methods: Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs. Results: Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-β/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-β1 and p-Smad2/3 in abdominal aortic tissues of SHRs. Conclusion: Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF-β1/Smad2/3 pathways

CCT6A knockdown suppresses osteosarcoma cell growth and Akt pathway activation in vitro.

We assessed the role of the protein-coding gene chaperonin-containing TCP1 subunit 6A (CCT6A) in osteosarcoma, as this is currently unknown. Using data from the R2 online genomic analysis and visualization application, we found that CCT6A messenger ribonucleic acid (RNA) expression is increased in osteosarcoma tissue and cells. Transfection of CCT6A small interfering RNA into cultured osteosarcoma cells revealed that CCT6A knockdown attenuates cell growth, cell viability, cell survival, and induced apoptosis and cell cycle progression at the G0/G1 phases. Moreover, CCT6A knockdown downregulated phospho-protein kinase B (p-Akt), cyclinD1 and B-cell lymphoma-2, whereas upregulated Bcl-2-associated X-protein expression. Thus, CCT6A knockdown inhibits cell proliferation, induces cell apoptosis, and suppresses the Akt pathway

Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of β-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM

Cellular microRNA miR-181b Inhibits Replication of Mink Enteritis Virus by Repression of Non-Structural Protein 1 Translation

<div><p>Mink enteritis virus (MEV) is one of the most important viral pathogens in the mink industry. Recent studies have showed that microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt) participate in host-pathogen interaction networks; however, whether or not miRNAs are involved in MEV infection has not been reported. Our study revealed that miRNA miR-181b inhibited replication of MEV in the feline kidney (F81) cell line by targeting the MEV non-structural protein 1 (NS1) messenger RNA (mRNA) coding region, resulting in NS1 translational repression, while MEV infection reduced miR-181b expression. This is the first description of cellular miRNAs modulating MEV infection in F81 cells, providing further insight into the mechanisms of viral infection, and may be useful in development of naturally-occurring miRNAs antiviral strategies.</p></div

MEV infection regulates cellular miRNAs including miR-181b.

<p>(<b>A</b>) Expression of selected miRNAs in F81 cells infected with MEV (MOI = 1) and in uninfected controls were tested for validation by qPCR using a specific primer for each miRNA. Fold increase/decrease was calculated based on endogenous control U6 small RNA normalization. (<b>B</b>) qPCR was used to detect the expression levels of miR-181b at 0 h, 6 h, 12 h, 24 h and 36 h after MEV infection, normalized to U6 small RNA. Data are from 3 independent experiments (mean ± SD). Statistical significance was analyzed by Student’s <i>t</i> test; * <i>P</i><0.05; ** <i>P</i><0.01; *** <i>P</i><0.001.</p

The conserved binding sites of miR-181b in the NS1 gene of pavovirus strains^a.

<p>^a Collected from NCBI 17 December 2012 and our lab sequencing.</p><p>^b The whole genome sequence of MEV in our lab is unpublished.</p><p>^c All the isolates of canine parvovirus from NCBI.</p><p>^d All the isolates of feline panleukopenia virus from NCBI.</p><p>^e Bold and italic sequences indicate conserved binding sites.</p

qPCR primers for miRNAs.

<p>qPCR primers for miRNAs.</p

miR-181b physically binds to MEV NS1 mRNA in the RISC.

<p>(<b>A</b>) Western blot assay was used to detect Ago2 protein from Ago2 immunoprecipitates of lysates from F81 cells. (<b>B</b>) qPCR analysis of the relative level of miR-181b and MEV NS1 mRNAs from Ago2 or IgG immunoprecipitated lysates of F81 cells transfected with miR-181b mimics (50 pmol/well) in 6-well plates and 12 h later infected with MEV (MOI = 0.1), using U6 small RNA as an internal control. (<b>D</b>) qPCR analysis of the relative level of endogenous miR-181b and MEV NS1 mRNAs from Ago2 or IgG immunoprecipitated lysates without transfection with the mimics. Data are from 3 independent experiments (mean ± SD). Statistical significance was analyzed by Student’s <i>t</i> test; * <i>P</i><0.05; ** <i>P</i><0.01.</p