Mono-sized sulfonated polystyrene (PS) microspheres were used as templates to prepare PS-zinc oxide (ZnO) core-shell microspheres. Two different hollow ZnO structures were obtained after removing the ...PS cores by solvent extraction or calcinations. However, we obtained rod-like ZnO by either using unsulfonated PS microspheres as templates or without any templates. Transmission electron microscope (TEM) and scanning electron microscope (SEM) images were used to characterize the structures and morphologies of all the samples. X-ray diffraction (XRD), electron diffraction (ED) and infrared (IR) spectra were, respectively, used to study the crystal structure and composition of samples, respectively.
Schematic illustration for the fabrication of PS-ZnO core-shell microspheres and hollow ZnO structures.
Abstract
Triple-negative breast cancer (TNBC) remains a difficult-to-treat cancer with a need for new therapeutic target. The serine/threonine protein phosphatase 2A (PP2A) functions as a tumor ...suppressor and enhancing PP2A activity by PP2A-activating agents is a promising anti-cancer approach. There are intrinsic inhibitors of PP2A including SET and cancerous inhibitor of protein phosphatase 2A (CIP2A), both of which interact and inhibit PP2A, playing oncogenic roles. Here we studied the tumor promoting effects of SET and CIP2A and discovered a potent linkage between SET and CIP2A-feedforward pathway in TNBC. We further demonstrated the anticancer activity of a novel SET/PP2A protein-protein interaction inhibitor, TD-19. Analyzing TCGA and clinical TNBC cohort, SET and CIP2A overexpressions correlated with worse survival in TNBC patients. Tumors from TNBC patients with higher SET expressions were significantly associated with higher Ki-67 and p-Akt expressions.
Table 1 High SET H score (>180) N=21Low SET H score (<=180) N=70P valueAge median (range)54 (36-69)56 (30-88)0.185Primary tumor (T) 0.99916 (28.6)21 (30.0) 213 (61.9)43 (61.4) 3-42 (9.5)6 (8.6) Nodal status (N) 0.12208 (38.1)45 (64.3) 17 (33.3)12 (17.1) 2-36 (28.6)13 (18.6) Stage 0.49812 (9.5)14 (20.0) 213 (61.9)41 (58.6) 36 (28.6)15 (21.4) Grade 0.78311 (4.8)4 (5.7) 28 (38.1)21 (30.0) 312 (57.1)45 (64.3) Tumor necrosis13 (61.9)40 (57.1)0.698Lymphovascular invasion6 (30.0)15 (21.4)0.549CIP2A median (range)120 (40-220)100 (30-300)0.253p-Akt median (range)200 (65-300)160 (20-300)0.011Ki-67 median (range)30 (0-87.5)22.5 (0-85)0.004
Consistent with clinical results, TNBC cells with ectopic overexpression of SET and CIP2A showed significantly increased cell proliferation, migration and invasion, and colony-formation. Moreover, TD-19 demonstrated anti-tumor effects through inhibiting SET-PP2A interaction and CIP2A/PP2A/pAkt-mediated pathway in vitro and in a TNBC xenograft mouse model. Mechanistically, TD19 downregulated CIP2A mRNA via affecting Elk-1 amount in nucleus thereby decreased the binding of Elk-1 to the CIP2A-promotor. Furthermore, given that ERK-dependent phosphorylation of Elk-1 is essential for Elk-1 shuttling from cytoplasm to nucleus and PP2A controls ERK activation (phosphorylation), we hypothesized a CIP2A-feedforward loop consisting of pERK/pElk-1/CIP2A/PP2A may contribute to the oncogenesis in TNBC. Indeed, with TD19 treatment, SET/PP2A interaction was inhibited, PP2A activity was increased, and expressions of the CIP2A-feedforward loop members were suppressed. This loop was validated by knockdown of PP2A and ectopic expression of Elk-1. In addition, ectopic expression of SET increased pAkt, pERK, pElk-1 and CIP2A expressions, suggesting a positive linkage between SET and CIP2A feedforward signaling. Importantly, combining TD-19 with cisplatin demonstrated enhanced anti-proliferative and apoptotic effects in association with CIP2A downregulation in vitro. In summary, we discover a novel oncogenic CIP2A-feedforward loop in TNBC and targeting SET to disrupt oncogenic CIP2A feedforward loop shows therapeutic potential in TNBC.
Citation Format: Huang T-T, Liu C-Y, Chen Y-T, Chu P-Y, Huang C-T, Wang W-L, Wu C-Y, Shiau C-W, Chen K-F, Tseng L-M. Targeting SET to disrupt oncogenic CIP2A feedforward loop shows therapeutic potential in triple negative breast cancer cells abstract. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-07-12.
We observe an obvious anomalous line shape of the e;{+}e;{-}--> hadrons total cross sections in the energy region between 3.700 and 3.872 GeV. It is inconsistent with the explanation for only one ...simple psi(3770) resonance with a statistical significance of 7sigma. The anomalous line shape may be explained by two possible enhancements of the inclusive hadron production near the center-of-mass energies of 3.764 and 3.779 GeV, indicating that either there is likely a new structure in addition to the psi(3770) resonance around 3.773 GeV, or there are some physics effects reflecting the DDover production dynamics.
We investigate the influence of non-N ewtonian micropolar fluids on the dynamic characteristics of wide tapered-land slider bearings. The study is carried out on the basis of the micro-continuum ...theory originally developed by Eringen (1966). Analytical expressions for the linear dynamic coefficients are provided and compared with earlier results in the literature. In particular, direct comparison with the Newtonian fluid-lubricated tapered-land bearings by Lin et al. (2006) indicates that the use of non-N ewtonian micropolar fluids can lead to a significant increase in the values of stiflness and damping coefficients. Such improvements are found to be even more pronounced for larger values of the non-N ewtonian parameters. Moreover, comparison with the non-Newtonian micropolar fluid-lubricated bearings with an inclined plane film by Naduvinamani and Marali (2007), leads to the conclusion that tapered-land bearings with large geometric parameters have higher dynamic stiflness coefficients. Furthermore, such bearings can provide better damping characteristics with respect to the case of inclined-plane bearings.
The mammalian renal collecting duct increases its water permeability in response to antidiuretic hormone (ADH). ADH causes cytoplasmic endosomes containing the water channel, aquaporin 2 (AQP 2), to ...fuse with the apical membrane so that the water permeability of the tubule increases many times above baseline. SNARE proteins are involved in the docking and fusion of vesicles with the cell membrane in neuron synapses. Whether these proteins are involved in the fusion of vesicles to the cell membrane in other tissues is not entirely clear. In the present study, we examined the role of SNARE proteins in the insertion of water channels in the collecting-duct response to ADH by using botulinum toxins A, B and C. Toxins isolated from clostridium botulinum are specific proteases that cleave different SNARE proteins and inactivate them. Tubules were perfused in vitro with botulinum toxin in the perfusate (50 nM for A and B and 15 nM for C). ADH (200 pM) was then added to the bath after baseline measurements of osmotic water permeability (P(f)) and the change in P(f) was followed for one hour. Botulinum toxins significantly inhibited the maximum P(f) by approximately 50%. Botulinum toxins A and C also decreased the rate of rise of P(f). Thus, SNARE proteins are involved in the insertion of the water channels in the collecting duct.
White spot syndrome virus (WSSV) can cause the most serious viral disease of shrimp and has a wide host range among crustaceans. Although researches show a lot about its genome and structure, ...information concerning the mechanism of how WSSV infects' cells is lacking. In this study, some experiments were applied to confirm the biological meaning of the protein–protein interaction between WSSV envelope protein, VP53A, and
Penaeus monodon chitin-binding protein (PmCBP). Immunofluorescent study indicated that PmCBP is located on the cell surface of host cells. PmCBP amounts of about 34
kDa can be detected in both
P. monodon and
Litopenaeus vannamei tissues by Western blotting. In the
in vivo neutralization experiment, both rVP53A and rPmCBP that were produced by
Esherichia coli can promote resp. a 40% and 20% survival rate of the shrimp which were challenged by WSSV. Furthermore, a yeast-two-hybrid result revealed that PmCBP could interact with at least 11 WSSV envelope proteins. Those findings suggest that PmCBP may be involved in WSSV infection.
In this paper, a new data hiding scheme for halftone images by pixel swapping is proposed, and the decryption process needs no computation. The proposed scheme generates a halftone stego-image with ...high visual quality, and the secret can be revealed in human vision system by stacking the stego-image with another designated halftone image. The quality of the revealed secret image is better than other existing schemes. In addition, the proposed scheme can cooperate with other existing data hiding schemes for halftone images to further increase the revealed secret quality without losing the characteristic of the original stego-image.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We report on a study of the process e+ e- → π± (DD*)∓ at sqrts = 4.26 GeV using a 525 pb(-1) data sample collected with the BESIII detector at the BEPCII storage ring. A distinct charged structure ...is observed in the (DD*)∓ invariant mass distribution. When fitted to a mass-dependent-width Breit-Wigner line shape, the pole mass and width are determined to be Mpole = (3883.9±1.5(stat)±4.2(syst)) MeV/c2 and Γpole = (24.8±3.3(stat)±11.0(syst)) MeV. The mass and width of the structure, which we refer to as Zc(3885), are 2σ and 1σ, respectively, below those of the Zc(3900) → π± J/ψ peak observed by BESIII and Belle in π+ π- J/ψ final states produced at the same center-of-mass energy. The angular distribution of the πZc(3885) system favors a JP = 1+ quantum number assignment for the structure and disfavors 1- or 0-. The Born cross section times the DD* branching fraction of the Zc(3885) is measured to be σ(e+ e- → π± Zc(3885)∓)×B(Zc(3885)∓ → (DD*)∓) = (83.5±6.6(stat)±22.0(syst)) pb. Assuming the Zc(3885) → DD* signal reported here and the Zc(3900) → πJ/ψ signal are from the same source, the partial width ratio (Γ(Zc(3885) → DD*)/Γ(Zc(3900) → πJ/ψ)) = 6.2±1.1(stat)±2.7(syst) is determined.
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