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Background Activating transcription factor-2 (ATF2) is a member of the basic leucine zipper family of DNA-binding proteins, which exhibits both oncogenic and tumor suppression activity in different tumors. However, the molecular mechanism of its dual function in cancer chemotherapy especially in gastric cancer has still not been elucidated. Methods The protein expression and location of ATF2 in gastric cancer tissues was detected with immunohistochemistry assay, and the clinical significance was analyzed using TCGA and GEO database. The activation and impact of ATF2 in cisplatin treated cells were evaluated with western blot, incucyte live cell analysis, clone formation and tumor xenografts assays. Interaction between ATF2 and p53 was confirmed with immunoprecipitation and GST-pull down. Potential molecular mechanism of ATF2 in different p53 status cells was analyzed with RNA sequencing and real-time quantitative PCR. Results ATF2 mainly located in the nucleus of cancer cells, higher ATF2 level was associated with poor five-year survival of gastric patients, especially in those undergone chemotherapy treatment. Cisplatin treatment significantly activated ATF2 in p53 mutant cells. ATF2 could interact with the trans-activation domain of p53 and enhance cisplatin sensitivity in p53 wild type cell lines, while promoted cell survival in mutant p53 cancer cells by affecting ERK1/2 pathway. Conclusions This study confirmed the effect of ATF2 on cisplatin sensitivity was associated with the functional status of p53 in gastric cancer cells. Integrated analysis of ATF2 expression and P53 status could be used to evaluate the chemotherapy sensitivity and prognosis of gastric cancer patients.

Mitochondria are dynamically regulated by fission and fusion processes. Silibinin induces apoptosis of MCF-7 and MDA-MB-231 human breast cancer cells. However, whether or not mitochondria dysfunction is involved in the apoptosis induction with silibinin of both types of the cells remains unknown. We here report that silibinin decreases the mitochondrial mass in terms of MitoTracker Green staining in both breast cancer cells. Silibinin induces morphological changes of mitochondria from oval to truncated or fragmented shapes accordingly. Condensed crests are observed in mitochondria by transmission electron microscopy. Silibinin causes mitochondrial membrane potential reduced. The expression of mitochondrial fission-associated proteins including dynamin-related protein 1 (DRP1) is up-regulated, whereas expression of the mitochondrial fusion-associated proteins, optic atrophy 1 and mitofusin 1, is down-regulated. In addition, silibinin treatment down-regulates ATP content as well as the levels of mitochondrial biogenesis-regulators including mitochondrial transcription factor A, peroxisome proliferator-activated receptor gamma coactivator 1 and nuclear respiratory factor 2. Moreover, treatments with DRP1 inhibitor, mdivi-1, or with DRP1-targetted siRNA efficiently prevent silibinin-induced apoptosis in the breast cancer cells, whereas inhibition of DRP1 phosphorylation with staurosporine increases apoptosis furthermore. Taken together, we conclude that silibinin impairs mitochondrial dynamics and biogenesis, leading to apoptosis of MCF-7 and MDA-MB-123 cells.

The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). The viability of T24 cells was estimated using a sulforhodamine B assay. Cell morphological changes were examined using Hoechst 33258 staining. The apoptotic rate was determined by staining cells with Annexin V-fluorescein isothiocyanate and propidium iodide labeling. The mitochondrial membrane potential (ΔΨm) was measured using 5,5,6,6-tetrachloro-1,1, 3,3-tetraethyl benzimidazole carbocyanine iodide. Alterations in the apoptosis-related regulators B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Bcl-2-interacting mediator of cell death (Bim), apoptotic protease-activating facter-1 (Apaf-1), caspase-9 and caspase-3 were determined using reverse transcription-polymerase chain reaction (PCR) and quantitative PCR methods. Western blot analysis was used to detect the expression of Bcl-2, Bax and caspase-3. CDK2 activity was measured using a spectrometric assay. Following treatment with ISL (between 30 and 70 µg/ml) for 24 h, typical apoptotic morphological changes were observed in T24 cells, exhibiting an edge set of chromosomes, nuclear condensation, nuclear fragmentation and other morphological features. Treatment with ISL increased the apoptotic ratio of T24 cells in a concentration-dependent manner and induced a decrease in the ΔΨm in a time-dependent manner. Treatment with ISL upregulated the expression of Bax, Bim, Apaf-1, caspase-9 and caspase-3, downregulated the expression of Bcl-2, and increased CDK2 activity. MK-8776 (an inhibitor of CDK2) antagonized the apoptosis induced by ISL, and, compared with treatment with ISL alone, pretreatment with MK-8776 inhibited the decrease in ΔΨm, downregulated the mRNA expression of Bax, Bim, Apaf-1, caspase-9 and caspase-3, and upregulated Bcl-2 mRNA expression. Western blot analysis demonstrated that, with increasing ISL concentration, the Bcl-2 expression level was significantly decreased (P

The ongoing Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has acutely highlighted the need to identify new treatment strategies for viral infections. Here we present a pivotal molecular mechanism of viral protein translation that relies on the mitochondrial translation machinery. We found that rare codons such as Leu-TTA are highly enriched in many viruses, including SARS-CoV-2, and these codons are essential for the regulation of viral protein expression. SARS-CoV-2 controls the translation of its spike gene by hijacking host mitochondria through 5’ leader and 3’UTR sequences that contain mitochondrial localization signals and activate the EGR1 pathway. Mitochondrial-targeted drugs such as lonidamine and polydatin significantly repress rare codon-driven gene expression and viral replication. This study identifies an unreported viral protein translation mechanism and opens up a novel avenue for developing antiviral drugs.One Sentence SummaryMitochondria are a potential target for antiviral therapy

Our previous studies showed that silibinin promoted activation of caspases to induce apoptosis in human breast cancer MCF-7 cells by down-regulating the protein expression level of estrogen receptor (ER) α and up-regulating ERβ. Recently, it has been reported that silibinin-induced apoptosis also involved nuclear translocation of apoptosis-inducing factor (AIF). Here we report that silibinin induces nuclear translocation of AIF through the down-regulation of ERα and up-regulation of ERβ in a concentration dependent manner in MCF-7 cells. AIF knockdown with siRNA significantly reverses silibinin-induced apoptosis. The nuclear translocation of AIF is enhanced by treatment with MPP, an ERα antagonist, and blocked with PPT, an ERα agonist. In contrast to ERα activity, the nuclear AIF is increased with an ERβ agonist, DPN and blocked with an ERβ antagonist, PHTPP. Autophagy, negatively regulated by ERα, positively controls AIF-mediated apoptosis, as evidenced by the preventive effect of autophagy inhibitor 3-MA and siRNA targeting LC3, on the nuclear translocation of AIF and cell death induced by silibinin co-treatment with or without MPP. In sum we conclude that AIF in nuclei is involved in silibinin-induced apoptosis, and the nuclear translocation of AIF is increased by down-regulated ERα pathway and/or up-regulated ERβ pathway in MCF-7 cells, accompanying up-regulation of autophagy.

Objective Emerging evidence showed that alteronol has a potential antitumour effect in several tumour cells. However, the antitumour effect of alteronol on breast cancer has not been reported. This study investigated the mechanisms of alteronol-induced cell proliferation inhibition in human breast cancer T47D cells. Methods After treatment with alteronol, T47D cell proliferation was examined by MTT assay. The cell cycle distribution, cell apoptosis, reactive oxygen species level and mitochondrial membrane potential were evaluated via flow cytometry. Next, the protein levels of cyclin B1, cdc2, p21, p-cyclin B1, p-cdc2, p53, Bax, Bcl-2 and cytochrome c were analysed using Western blot analysis. Meanwhile, the mRNA levels of cyclin B1, cdc2, p21 and p53 were examined by qRT-PCR. Key findings Our data showed that alteronol inhibited the proliferation of T47D cells via inducing G2-phase arrest and cell apoptosis. Compared with control group, alteronol significantly increased ROS level and triggered mitochondrial dysfunction in alteronol-treated T47D cells. Further studies showed that the mRNA and protein levels of cdc2 and cyclin B1 were downregulated, while the mRNA and protein levels of p21, p53, p-cyclin B1, p-cdc2 and cytochrome c were upregulated. In addition, the expression level of Bax was increased, and the expression level of Bcl-2 was decreased. Conclusions Alteronol induced T47D cell cycle arrest and cell apoptosis through increasing ROS production and triggering mitochondrial dysfunction, and subsequently inhibiting T47D cell proliferation.

The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). The viability of T24 cells was estimated using a sulforhodamine B assay. Cell morphological changes were examined using Hoechst 33258 staining. The apoptotic rate was determined by staining cells with Annexin V-fluorescein isothiocyanate and propidium iodide labeling. The mitochondrial membrane potential (ΔΨm) was measured using 5,5,6,6-tetrachloro-1,1, 3,3-tetraethyl benzimidazole carbocyanine iodide. Alterations in the apoptosis-related regulators B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Bcl-2-interacting mediator of cell death (Bim), apoptotic protease-activating facter-1 (Apaf-1), caspase-9 and caspase-3 were determined using reverse transcription-polymerase chain reaction (PCR) and quantitative PCR methods. Western blot analysis was used to detect the expression of Bcl-2, Bax and caspase-3. CDK2 activity was measured using a spectrometric assay. Following treatment with ISL (between 30 and 70 µg/ml) for 24 h, typical apoptotic morphological changes were observed in T24 cells, exhibiting an edge set of chromosomes, nuclear condensation, nuclear fragmentation and other morphological features. Treatment with ISL increased the apoptotic ratio of T24 cells in a concentration-dependent manner and induced a decrease in the ΔΨm in a time-dependent manner. Treatment with ISL upregulated the expression of Bax, Bim, Apaf-1, caspase-9 and caspase-3, downregulated the expression of Bcl-2, and increased CDK2 activity. MK-8776 (an inhibitor of CDK2) antagonized the apoptosis induced by ISL, and, compared with treatment with ISL alone, pretreatment with MK-8776 inhibited the decrease in ΔΨm, downregulated the mRNA expression of Bax, Bim, Apaf-1, caspase-9 and caspase-3, and upregulated Bcl-2 mRNA expression. Western blot analysis demonstrated that, with increasing ISL concentration, the Bcl-2 expression level was significantly decreased (P

BACKGROUND AND PURPOSE The aim of the present study was to investigate the effects and possible mechanisms of dioscin against pancreatic cancer in vitro and in vivo. EXPERIMENTAL APPROACH In vitro actions of dioscin on ASPC-1 and PANC-1 cells, and in vivo effects to suppress the tumor growth of cell xenografts in nude mice were carried out. In addition, microRNA microarray analysis was used to find the differential expressed microRNAs caused by dioscin. Then, the mechanisms of dioscin against pancreatic cancer were carried out. KEY RESULTS Dioscin markedly induced apoptosis and significantly suppressed the tumor growth of ASPC-1 and PANC-1 cell xenografts. Total of 107 microRNAs with differential changes were found, in which miR-149-3P targeted with AKT1 was markedly up- regulated by dioscin. Further studies showed that dioscin significantly down- regulated AKT1 levels, and thus induced cell apoptosis by increasing the levels of Bax, Apaf-1, cleaved caspase-3/9, cleaved PARP, suppressing Bcl-2 levels, and causing Cytochrome c release. In addition, inhibitor of miR-149-3P and siRNA of AKT1 testes suggested that diosicn showed excellent activity against pancreatic cancer via miR- 149-3P-mediated inhibition of AKT1 signaling pathway. CONCLUSIONS AND IMPLICATIONS Collectively, these findings confirmed the potent effects of dioscin against pancreatic cancer and also provided novel insights into the mechanisms of the compound as one potential candidate for the treatment of pancreatic cancer in the future.

To efficiently separate the photo-generated electron–hole pairs of TiO 2 hybrid, anatase TiO 2 nanorod assembly grafted reduced graphene oxides (rGO@TiO 2 -NR) hybrid was successfully fabricated using potassium titanium oxalate (PTO) and graphene oxides (GO) as starting materials and diethylene glycol (DEG) as reductant. The effect of GO content on the structure and photocatalytic activity of rGO@TiO 2 -NR composite was systematically studied. Results show that, in the absence of GO, only TiO 2 microsphere assembly is obtained from TiO 2 nanorods. The presence of GO results in the formation of a flake-like TiO 2 -nanorod-assembled grafted rGO hybrid. The photocatalytic activity of rGO@TiO 2 -NR composite increases first and then decreases with increase in the amount of GO from 0 wt.% to 10 wt.%. The hybridized S4 sample prepared with 4 wt.% GO possesses the highest photocatalytic activity with a constant rate of 0.039 min −1 in the photocataytic degradation of Brilliant X-3B dye (X3B); this sample was enhanced more than three times when compared with pure TiO 2 sample (0.012 min −1 ). The enhanced photocatalytic activity of the rGO@TiO 2 -NR hybrid was attributed to the strong interaction between TiO 2 nanorods and rGO. The unique hierarchical structure of 1D nanorod assembly TiO 2 –rGO flakes facilitates the injection and transfer of photo-generated electrons from TiO 2 to graphene, thus retarding the recombination of electron–hole pairs and enhancing the photocatalytic activity. The enlarged BET surface areas, not only increasing the number of active sites, but also facilitating the adsorption of the dye, and improved light-harvesting ability also contribute to the enhanced photoreactivity of rGO@TiO 2 -NR hybrid.

We reported previously that higher doses (150–250 μM) of silibinin enhanced fission and inhibited fusion of mitochondria, accompanying apoptosis of double-positive breast cancer cell line MCF-7 cells and triple-negative breast cancer cell line MDA-MB-231 cells. We report here three important questions yet unclarified in the previous study; 1) Whether enhanced fission of mitochondria by the treatment of silibinin leads to mitophagy, 2) Whether mitophagy positively contributes to apoptosis and 3) Whether estrogen receptor-positive (ER+) MCF-7 cells and estrogen receptor-negative (ER−) MDA-MB-231 cells are affected in a different way by silibinin treatment, since silibinin often works through ERs signaling pathway. Mitophagy driven by Pink1/Parkin signaling, plays an important role in eliminating damaged mitochondria. Indeed, increased expression of Pink1 and the recruitment of Parkin and LC3-II to mitochondria by the treatment with silibinin account for silibinin induction of mitophagy. In this study, the effects of mitochondrial division inhibitor 1 (mdivi-1) and small interfering RNA targeting dynamin-related protein 1 (DRP1) were examined to reveal the effect of mitochondrial fission on mitophagy. As expected, mdivi-1 or siRNA targeting DRP1 reversed silibinin-induced mitochondrial fission due to down-regulation in the expression of DRP1. Inhibition of mitochondrial fission by mdivi-1 prevented induction of mitophagy as well as autophagy in both MCF-7 and MDA-MB-231 cells, indicating that silibinin-induced mitochondrial fission leads to mitophagy. Inhibition of mitochondrial fission efficiently prevented silibinin-induced apoptosis in MCF-7 and MDA-MB-231 cells in our previous work, and the second point of the present study, inhibition of mitophagy by Pink1 or Parkin knockdown increased silibinin-induced apoptosis of these cells, respectively, suggesting that the mitophagy induced by silibinin treatment serves as a cytoprotective effect, resulting in reduction of apoptosis of cancer cells in both cells. In the third point, we studied whether estrogen receptors (ERs) played a role in silibinin-induced mitophagy and apoptosis in MCF-7 and MDA-MB-231 cells. ERα and ERβ are not involved in silibinin-induced mitophagic process in MCF-7 and MDA-MB-231 cells. These findings demonstrated that silibinin induced mitochondria fission leads to mitophagy, which attenuates silibinin-induced apoptosis not through ERs-Pink1 or -Parkin pathway in MCF-7 and MDA-MB-231.

Human triple negative breast cancer cells, MDA-MB-231, show typical epithelial to mesenchymal transition associated with cancer progression. Mitochondria play a major role in cancer progression, including metastasis. Changes in mitochondrial architecture affect cellular migration, autophagy and apoptosis. Silibinin is reported to have anti-breast cancer effect. We here report that silibinin at lower concentrations (30–90 μM) inhibits epithelial to mesenchymal transition (EMT) of MDA-MB-231, by increasing the expression of epithelial marker, E-cadherin, and decreasing the expression of mesenchymal markers, N-cadherin and vimentin. Besides, silibinin inhibition of cell migration is associated with reduction in the protein expression of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) and paxillin. In addition, silibinin treatment increases mitochondrial fusion through down-regulating the expression of mitochondrial fission-associated protein dynamin-related protein 1 (DRP1) and up-regulating the expression of mitochondrial fusion-associated proteins, optic atrophy 1, mitofusin 1 and mitofusin 2. Silibinin perturbed mitochondrial biogenesis via down-regulating the levels of mitochondrial biogenesis regulators including mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor gamma coactivator (PGC1) and nuclear respiratory factor (NRF2). Moreover, DRP1 knockdown or silibinin inhibited cell migration, and MFN1&2 knockdown restored it. Mitochondrial fusion contributes to silibinin’s negative effect on cell migration. Silibinin decreased reactive oxygen species (ROS) generation, leading to inhibition of the NLRP3 inflammasome activation. In addition, knockdown of mitofusin 1&2 (MFN 1&2) relieved silibinin-induced inhibition of NLRP3 inflammasome activation. Repression of ROS contributes to the inhibition of the expression of NLRP3, caspase-1 and IL-β proteins as well as of cell migration. Taken together, our study provides evidence that silibinin impairs mitochondrial dynamics and biogenesis, resulting in reduced migration and invasion of the MDA-MB-231 breast cancer cells.

Background: Isoliquiritigenin (ISL) is a licorice chalcone. According to CN104758274, CN101658513 and US009089546, it is claimed that ISL has anti-inflammatory, anti-oxidative, and anti-tumoral effects. Objective: This study aimed to investigate the potential therapeutic effect of ISL in mouse melanoma B16F10 cells. Methods: Sulforhodamine B (SRB) colorimetric assay was used to test the effects of ISL on proliferation. Commercial assay kits were applied to assess glucose uptake, lactate production and ATP levels. Measurement of apoptosis was involved with Hoechst 33258, JC-1 and annexin V-FITC/PI staining. H2DCFDA probe was employed to detect ROS generation. Quantitative RT-PCR and western blot were utilized to measure the mRNA and protein levels. Results: ISL abated hypoxia-inducible factor 1 (HIF-1 ) stability and reduced a series of glycolysis-relevant enzymes expression, including glucose transporters 1/4 (GLUT 1/4), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Exposure to ISL induced the mitochondrial membrane potential depolarization and increased intracellular reactive oxygen species (ROS) level. ISL could effectively inhibit proliferation and alleviate hypoxia in mouse melanoma B16F10 cells via inducing apoptosis and reducing the expression of significant enzymes in the glycolysis. ISL significantly inhibited B16F10 cell proliferation via inducing apoptosis, and alleviated hypoxia by recovering mitochondrial function and reversing high glycolysis. Conclusion: Our findings propose that ISL can be a promising therapeutic agent for the melanoma via reliving hypoxia of microenvironment and targeting energy metabolism system of cancer cells. Consistent with WO2015079213 and WO2014084494, targeting glycolysis can be an effective means to anti-cancer.

The aim of the present study was to determine the effects of Licochalcone D (LD) on the apoptosis and migration and invasion in human melanoma A375 cells. Cell proliferation was determined by sulforhodamine B assay. Apoptosis was assessed by Hoechst 33258 and Annexin V-FITC/PI staining and JC-1 assay. Total intracellular reactive oxygen species (ROS) was examined by DCFH-DA. Wound healing and Transwell assays were used to detect migration and invasion of the cells. The activities of matrix metalloproteinase (MMP-2 and MMP-9) were assessed via gelatin zymography. Tumor growth in vivo was evaluated in C57BL/6 mice. RT-PCR, qPCR, ELISA and western blot analysis were utilized to measure the mRNA and protein levels. Our results showed that LD inhibited the proliferation of A375 and SK-MEL-5 cells in a concentration-dependent manner. After treatment with LD, A375 cells displayed obvious apoptotic characteristics, and the number of apoptotic cells was significantly increased. Pro-apoptotic protein Bax, caspase-9 and caspase-3 were upregulated, while anti-apoptotic protein Bcl-2 was downregulated in the LD-treated cells. Meanwhile, LD induced the loss of mitochondrial membrane potential (ΔΨm) and increased the level of ROS. ROS production was inhibited by the co-treatment of LD and free radical scavenger N-acetyl-cysteine (NAC). Furthermore, LD also blocked A375 cell migration and invasion in vitro which was associated with the downregulation of MMP-9 and MMP-2. Finally, intragastric administration of LD suppressed tumor growth in the mouse xenograft model of murine melanoma B16F0 cells. These results suggest that LD may be a potential drug for human melanoma treatment by inhibiting proliferation, inducing apoptosis via the mitochondrial pathway and blocking cell migration and invasion.

Fabrication of TiO2 hollow microspheres (TiO2-HMSs) has attracted considerable attention owing to their low density, high photoreactivity, and easy to separate and reuse. A fluoride-free method for the fabrication of TiO2-HMSs is reported by refluxing a mixed solution of H3PW12O40 (0.4 mmol), KCl (2.5 mmol) and Ti(SO4)2 (2–25 mmol) at 125 °C for 8 h, followed by decomposition of the K3PW12O40 (KPW) template in basic solution. The prepared TiO2-HMSs are characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy and X-ray photoelectron spectroscopy. The activities of the photocatalysts are evaluated by photocatalytic degradation of Brilliant Red X-3B, an anionic dye, under UV irradiation. It is observed that the TiO2-HMSs exhibit diameters of approximately 0.5–1 μm, and the photocatalytic activity of TiO2-HMSs initially increases and then decreases with an increasing amount of Ti(SO4)2. The TiO2-HMSs prepared in the presence of 4 mmol Ti(SO4)2 exhibit the highest photocatalytic activity, which is 2.1 times higher than TiO2 nanoparticles (prepared in the absence of the KPW template). The enhanced photocatalytic activity of the prepared TiO2-HMSs is ascribed to the improved crystallization, coupling effect between TiO2 and the residual KPW template, and the unique hollow structures of TiO2-HMSs.

TiO2 hollow microspheres (TiO2-HMSs) have attracted much attention due to their low density, high photoreactivity and easy recovery. However, fabrication of TiO2-HMSs is time-consuming and costly. In this paper, effect of H2O2 on the formation of chain-like TiO2-HMSs was studied using (NH4)2TiF6 as titanium source and urea as neutralizer through a one-pot hydrothermal reaction strategy. The prepared TiO2-HMSs were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM) and scanning electron microscopy (SEM). The photocatalytic activity of TiO2-HMSs was evaluated by photocatalytic degradation of an anionic dye X3B under UV irradiation. It was found that the presence of H2O2 not only influences the nucleation, but also enhances the hollowing process of TiO2-HMSs by accelerating the “inside-outside” mass transfer. TiO2-HMSs prepared in the presence of H2O2 showed enhanced photocatalytic activity due to the synergistic effects of well crystallization and hollow structures.

Background Phytoestrogens have been proposed as replaceable medicines for climacteric hormone replacement therapy, on the basis of EP3138562 and US5516528. However, recent studies demonstrated that phytoestrogens might promote the proliferation of breast cancer cells, which is rooted in their estrogenic activity. Acacetin, as one phytoestrogen, has been reported to exhibit estrogenic activity. But the effect of acacetin on breast cancer cells proliferation and its mechanism has not been explored. Objective This study aims to evaluate the effects of acacetin on breast cancer MCF-7 cells proliferation and to explore its possible mechanism. Methods Sulforhodamine B (SRB) assay was used to test the proliferation rate of MCF-7 cells. Flow cytometry was utilized to determine cell cycle. RT-qPCR and western blot were employed to evaluate the expressions of proliferation-related factors in mRNA and protein levels. Results According to SRB assay and flow cytometric analysis, low dose of acacetin from 10-3 to 1µM promoted the MCF-7 cells proliferation in a dose-dependent and time-dependent manner. Moreover, the expressions of cell cycle-related molecules, ERK1/2 and PI3K/AKT were increased after treatment with acacetin, while the increases were effectively reversed by ER antagonist ICI 182,780. Further studies showed that acacetin notably induced increasing mRNA and proteins levels of ERα, which were strongly reversed by ERα antagonist MPP. Conclusion Low dose of acacetin from 10-3 µM to µM promoted the proliferation of MCF-7 cells through the ERK/PI3K/AKT pathway and its downstream cyclin signaling. And ERα is mainly responsible for acacetin promoting proliferation in MCF-7 cells.

TiO 2 hollow microspheres (TiO 2 –HMSs) have attracted great interest in recent years due to their unique physical and chemical properties such as low density, high surface area and effective light-harvesting property. In this paper, anatase TiO 2 –HMSs were synthesized by hydrothermal treatment of amorphous TiO 2 microspheres precursor in the presence of ammonia solution at 180 °C. The prepared TiO 2 –HMSs were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM) and scanning electron microscopy (SEM). It was found that the presence of ammonia accelerates the hollowing process of TiO 2 microspheres, and the phase transformation from amorphous TiO 2 to metastable ammonium titanate occurs firstly and then to anatase TiO 2 phase, forming fluffy core/shell and yolk/shell structured microspheres. The photocatalytic activity of the photocatalyst was evaluated both by photocatalytic degradation of cationic dye (Rhodamine B) and anionic dye (Brilliant Red X-3B) under UV irradiation. The calcined fluffy core/shell structured TiO 2 microspheres with a hydrothermal reaction time of 18 h showed the highest photocatalytic activity. Ammonia-induced self-transformation mechanism was also proposed for the formation of TiO 2 –HMSs.

Ti3+ self-doped TiO2 nanosheets with dominant {0 0 1} facets for excellent visible-light photocatalytic activity were prepared by a facile one-pot hydrothermal reaction strategy using tetrabutyl titanate (TBT) as titanium source, hydrofluoric acid (HF) as structure-directing agent and zinc powder (Zn) as reductant. The synthesized catalysts were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectra (XPS), diffuse reflectance spectrum (DRS) and nitrogen adsorption–desorption isotherms. The photocatalytic activity of the photocatalyst was evaluated by measure the formation rate of photo-induced hydroxyl radicals ( OH) under visible-light irradiation (λ = 420 ± 10 nm) using coumarin as a probe. It was found that the presence of zinc shows little effect on the morphology, phase structure, BET surface areas and pore structure. However, the addition of Zn powder resulted in the formation of Ti3+ self-doped anatase TiO2 nanosheets with dominant {0 0 1} facets, which is responsible for the enhanced visible-light photocatalytic activity. The sample prepared with zinc/TBT molar ratio of 0.3 showed the highest visible-light photocatalytic activity, which is 1.9 times higher than that of commercial P25 TiO2.

This paper proposes a design of wireless sensor network gateways based on ARM to solve the poor performance of the network, and low efficiency of communication, which is caused by the poor computing capacity and limited bandwidth in wireless sensor network (WSN). The paper introduces the composition and characteristics of the gateways, and the design of their hardware and software. In this design, the data is transmitted by the network nodes to the gateways with the help of ZigBee near field communication (NFC) technology after its collection, and then the gateways transmit the data to the monitoring center through GPRS. It makes high performance of long distance transmission and the holding of gateways online come true.

This project is a research of wind speed measurement system, with a high-precision, low-power, whose control core uses the Samsung S3C2410 32-bit microprocessor with high performance, low power consumption. The system adopts the LCD, and can display the current value of wind speed and wind direction which can be transmitted by ZigBee. The system can set up two limit of wind speed corresponding to two alarms, two relay outputs, and any configuration. The system has simple operation, eye-catching display, reliable performance, and can be widely used in meteorology, civil aviation, highway, construction, energy and other industries.

The aim of the present study was to investigate the effects and possible underlying mechanisms of dioscin against pancreatic cancer in vitro and in vivo.In vitro actions of dioscin on viability of ASPC-1 and PANC-1 cells, and in vivo effects to suppress the tumour growth of cell xenografts in nude mice were assessed. In addition, microRNA microarray analysis determined which microRNAs were affected by dioscin. The mechanisms underlying the actions of dioscin against pancreatic cancer were elucidated in terms of Akt1 and other proteins related to aopoptosis.Dioscin markedly induced apoptosis and significantly suppressed the tumour growth of ASPC-1 and PANC-1 cell xenografts, in nude mice. Total of 107 microRNAs with differential changes were found, in which miR-149-3P targeted with Akt1 was markedly up-regulated by dioscin. Further studies showed that dioscin significantly down-regulated Akt1 levels, and thus induced cell apoptosis by increasing the levels of Bax, Apaf-1, cleaved caspase-3/9, cleaved PARP, suppressing Bcl-2 levels, and causing cytochrome c release. The effects of an inhibitor of miR-149-3P and of siRNA of testicular Akt1 suggested that dioscin showed excellent activity against pancreatic cancer via miR- 149-3P-mediated inhibition of Akt1 signalling pathway.Collectively, these findings confirmed the potent effects of dioscin against pancreatic cancer and also provided novel insights into the mechanisms of the compound as a potential candidate for the treatment of pancreatic cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Publisher.The authors have plagiarized a paper that had already appeared in “Queen's 25th Biennial Symposium on Communications”, page 168-172, print ISBN 978-1-4244-5709-0, http://dx.doi.org/10.1109/BSC.2010.5472979.One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

The anti-cancer effects of dioscin have been widely reported. However, its effect on laryngeal cancer remains unknown. In the present paper, our results showed that dioscin markedly caused cell apoptosis and DNA damage, increased reactive oxygen species (ROS) level, induced S-phase arrest, and inhibited invasion of human laryngeal cancer HEp-2 and TU212 cells. Mechanism investigation showed that dioscin markedly up-regulated p53 level, and down-regulated cyclin-dependent kinase 2 (CDK2) and Cyclin A levels. In addition, dioscin significantly down-regulated the levels of p-ERK, Bcl-2, up-regulated the levels of p-JNK, p-p38, Bax, cleaved caspase-3/-9, and caused Cytochrome c release. Furthermore, U0126, an ERK1/2 inhibitor, markedly down-regulated Bcl-2 level, up-regulated the levels of Bax, cleaved caspase-3/9, and enhanced Cytochrome c release inducted by dioscin. While, SP600125 (one JNK inhibitor) and SB203580 (one p38 inhibitor) markedly up-regulated Bcl-2 level, down-regulated the levels of Bax, cleaved caspase-3/9, and obviously boosted Cytochrome c release induced by dioscin. Interestingly, dioscin also markedly down-regulated the levels of MMP2 and MMP9 associated with tumor invasion. Taken together, our study indicated that dioscin suppressed laryngeal cancer cells growth via inducting cell-cycle arrest, MAPK-mediated mitochondrial- derived apoptosis and inhibiting tumor invasion, which could be used as one potential candidate for the treatment of laryngeal cancer in the future.

According to the fuzziness of assessment system about university scientific research capability, this paper puts forward to a comprehensive judgment method basis on improved discredited Hopfield neural network to establish assessment model and studies with examples. It indicates that it is a practical and simple assessment model with a higher resolution and actual assessment results and it offers scientific reference for recognizing university scientific research capability, self-diagnosis and adjustment as well as promoting university ranking.

Web-based scientific research collaboration system is in accordance with requirement of university scientific research; through analyzing the richness of communication media, it has selected scientific research collaboration system to be as the communication media, has analyzes and designed the system function structure, then to analyze system implementation and develop system through three-layer applicative structure, system security strategy, identity authentication mechanism, Web security and backup strategy. System program has reasonable structure, complete function, friendly interface, and it is easy to control and use; system has the strong expansibility, portability, security and allsideness of data.

We have shown how the nature of the rough relational database provides some inherent security through its use of non-first normal form structure. Moreover, we provided measures of database security based on information-theoretic measures that allow for the evaluation of numeric measures for entropy. We are currently investigating the extension of this work for fuzzy rough and intuitionist relational databases.

This work is the first step in the development of a centralized decision making agent for the IWARD project that is the extension of two difficult problems VRP-TW and the MC-VRP combined together. In this paper we presented the problem and proposed a resolution method using the evolutionary algorithms. Improving the local search algorithms and the crossover techniques, taking into account the mission duration, not only the order of the missions would be important avenues for future improvements, but also the variation of the parameters mainly the mutation factor and population sizes could be also beneficial.

In this study, a self-organizing quantum evolutionary algorithm for multi-objective optimization (MSQEA) is proposed. Because of the quantum dynamic mechanism all the subpopulations may move concurrently in a force-field until all of them reach their equilibrium states. We estimate the performance of algorithm. The efficiency of the approach has been illustrated by applying to 0/1 Multi-objective knapsack problems. The results show that MSQEA can yield improvement in solution quality.

In the field of J2EE，MVC framework exists crosscutting concerns across multiple modules (e.g. logging, validation, transaction etc.) causing the code scattering and code confusion and making the system difficult to maintain and to extend. Fortunately, Aspect-Oriented Programming aims at addressing the problems of them. Aspects can be defined to modularize such concerns. In this work, we introduce the aspect-oriented programming ideas into the MVC model, and propose a model of aspect-oriented MVC framework, which extracts crosscutting concerns of going through the system to form an aspect layer and uses the configuration file to statement the point of weaving. Finally, we report the results of the framework of the feasibility and superiority by an actual project development.

Information and digital age presents tremendous opportunity to the development of embedded products and shows the embedded market a prosperous prospect, Web server embedded in equipment can provide uniform operation and control interface based on browser mode for any legal user accessing to its network, browser has become the front control board of equipment and a hot spot for development in recent years. This paper introduces in detail the transplantation and system software design of embedded Web server, methods of constructing Boa Web server under a constructed ARM+μCLinux development platform and design and realization process of remote monitoring application program.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Publisher.The authors have plagiarized a paper that had already appeared in “Queen's 25th Biennial Symposium on Communications”, page 168-172, print ISBN 978-1-4244-5709-0, http://dx.doi.org/10.1109/BSC.2010.5472979.One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.