MOF upregulates the estrogen receptor α signaling pathway by its acetylase activity in hepatocellular carcinoma.

The histone acetyltransferase MOF (KAT8) is mainly involved in the acetylation of histone H4 at lysine 16 (H4K16) and some non-histone proteins. The MOF expression level is significantly reduced in many cancers, however the biological function of MOF and its underlying mechanism are still elusive in hepatocellular carcinoma (HCC). Estrogen receptor α (ERα) has been considered as a tumor suppressor in HCC. Here, we demonstrated that MOF expression is significantly reduced in HCC samples, and is positively correlated with that of ERα. MOF interacts with ERα, and participates in acetylation of ERα at K266, K268, K299, thereby inhibiting ERα ubiquitination to maintain the stability of ERα. In addition, MOF participates in the upregulation of ERα-mediated transactivation. Depletion of MOF significantly promotes cell growth, migration, and invasion in HCC cell lines. Taken together, our results provide new insights to understand the mechanism underlying the modulation function of MOF on ERα action in HCC, suggesting that MOF might be a potential therapeutic target for HCC.

Splicing factor PRPF6 upregulates oncogenic androgen receptor signaling pathway in hepatocellular carcinoma.

Androgen receptor (AR) signaling is considered to be crucial for the pathogenesis of hepatocellular carcinoma (HCC) with obvious sexual dimorphism. Pre-mRNA processing factor 6 (PRPF6) was identified as a coactivator of AR. However, the molecular mechanism underlying the modulation function of PRPF6 on AR-mediated transcriptional activity in HCC needs to be further clarified. In this study, we analyzed data from The Cancer Genome Atlas to show that PRPF6 is highly expressed in HCC. . Our data indicated that PRPF6 interacts with AR/AR splice variants (AR-Vs) and upregulates AR/AR splice variant 7-mediated transcriptional activity even without dihydrotestosterone treatment. We observed that AR is obviously induced by androgen treatment and is mainly expressed in the nucleus in HCC-derived cell lines. Moreover, overexpression of PRPF6 enhances AR expression accompanied with the increase of AR-Vs expression. We provided evidence that PRPF6 participates in upregulating AR self-transcription. PRPF6 facilitates the recruitment of AR to the androgen responsive element region of the AR gene. Finally, PRPF6 depletion inhibits cell proliferation in HCC cells and mouse xenografts. Taken together, our results suggest that PRPF6 as a splicing factor enhances AR self-transcription, thereby coactivating oncogenic AR/AR-Vs actions in HCC.

Preparation of poly-dopamine-silk fibroin sponge and its dye molecular adsorption.

This paper proposes a process for fabricating a poly-dopamine-silk fibroin sponge (PDA-SF) by using dopamine self-assembly and coating the skeleton of a silk fibroin sponge. The PDA-SF sponge was characterized by SEM, TEM, XPS, XRD and FT-IR. It was found that the sponge exhibits sheet structures with a pore size of 60 ± 20 µm and poly-dopamine adhered to the surface of pure silk fibroin through noncovalent bond forces. With a hierarchical porous structure, the derived sponge provides fast flow channels and abundant active sites, which will benefit the diffusion and removal of cationic dyes. Batch adsorption and dynamic adsorption of crystal violet (CV) were studied. The batch adsorption capacity of the PDA-SF sponge for CV increased with its PDA content. Under a dynamic adsorption mode, the adsorption efficiency of the PDA-SF sponge for CV (5 mg/L, 200 mL) can reach up to 98.2% after 12 min, whereas it is only 90.2% under stationary mode after 72 h. Furthermore, the sponge shows an outstanding smart adsorption performance. More importantly, the composite sponge still keeps high separation and adsorption efficiencies after 20 cycles, and the appearance remains good.

Why does mobile payment promote purchases? Revisiting the pain of paying, and understanding the implicit pleasure via selective attention.

The past years have witnessed a phenomenal growth of the mobile payment market, but how mobile payment affects purchase behavior receives less attention from academics. Recent studies suggested that lower pain of paying may not fully clarify the relationship between mobile payment and increased purchases (i.e., mobile payment effect). The current research first introduced price level in Study 1 and demonstrated that the pain of paying served as an underlying mechanism only in the high-price condition rather than the low-price condition. As such, Study 2 was conducted in a low-price context to address the uncovered mechanisms. We propose a new concept of "pleasure of payment" that is defined as an implicit and consumption-related hedonic response based on the cue theory of consumption. By tracking spontaneous attention to positive attributes (i.e., benefits) of products, Study 2 demonstrated this implicit pleasure as a psychological mechanism for the mobile payment effect when the pain of paying was not at play. These findings have important implications for mobile payment in research and practice by identifying price level as a boundary condition for the role of pain of paying and understanding the positive downstream consequences of mobile payment usage on consumer psychology.

MYSM1 acts as a novel co-activator of ERα to confer antiestrogen resistance in breast cancer.

Endocrine resistance is a crucial challenge in estrogen receptor alpha (ERα)-positive breast cancer (BCa). Aberrant alteration in modulation of E2/ERα signaling pathway has emerged as the putative contributor for endocrine resistance in BCa. Herein, we demonstrate that MYSM1 as a deubiquitinase participates in modulating ERα action via histone and non-histone deubiquitination. MYSM1 is involved in maintenance of ERα stability via ERα deubiquitination. MYSM1 regulates relevant histone modifications on cis regulatory elements of ERα-regulated genes, facilitating chromatin decondensation. MYSM1 is highly expressed in clinical BCa samples. MYSM1 depletion attenuates BCa-derived cell growth in xenograft models and increases the sensitivity of antiestrogen agents in BCa cells. A virtual screen shows that the small molecule Imatinib could potentially interact with catalytic MPN domain of MYSM1 to inhibit BCa cell growth via MYSM1-ERα axis. These findings clarify the molecular mechanism of MYSM1 as an epigenetic modifier in regulation of ERα action and provide a potential therapeutic target for endocrine resistance in BCa.

BAP18 facilitates CTCF-mediated chromatin accessible to regulate enhancer activity in breast cancer.

The estrogen receptor alpha (ERα) signaling pathway is a crucial target for ERα-positive breast cancer therapeutic strategies. Co-regulators and other transcription factors cooperate for effective ERα-related enhancer activation. Recent studies demonstrate that the transcription factor CTCF is essential to participate in ERα/E2-induced enhancer transactivation. However, the mechanism of how CTCF is achieved remains unknown. Here, we provided evidence that BAP18 is required for CTCF recruitment on ERα-enriched enhancers, facilitating CTCF-mediated chromatin accessibility to promote enhancer RNAs transcription. Consistently, GRO-seq demonstrates that the enhancer activity is positively correlated with BAP18 enrichment. Furthermore, BAP18 interacts with SMARCA1/BPTF to accelerate the recruitment of CTCF to ERα-related enhancers. Interestingly, BAP18 is involved in chromatin accessibility within enhancer regions, thereby increasing enhancer transactivation and enhancer-promoter looping. BAP18 depletion increases the sensitivity of anti-estrogen and anti-enhancer treatment in MCF7 cells. Collectively, our study indicates that BAP18 coordinates with CTCF to enlarge the transactivation of ERα-related enhancers, providing a better understanding of BAP18/CTCF coupling chromatin remodeling and E-P looping in the regulation of enhancer transcription.

USP22 upregulates ZEB1-mediated VEGFA transcription in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common solid tumor with high rate of recurrence and mortality. Anti-angiogenesis drugs have been used for the therapy of HCC. However, anti-angiogenic drug resistance commonly occurs during HCC treatment. Thus, identification of a novel VEGFA regulator would be better understanding for HCC progression and anti-angiogenic therapy resistance. Ubiquitin specific protease 22 (USP22) as a deubiquitinating enzyme, participates in a variety of biological processes in numerous tumors. While the molecular mechanism underlying the effects of USP22 on angiogenesis is still needed to be clarified. Here, our results demonstrated that USP22 acts as a co-activator of VEGFA transcription. Importantly, USP22 is involved in maintenance of ZEB1 stability via its deubiquitinase activity. USP22 was recruited to ZEB1-binding elements on the promoter of VEGFA, thereby altering histone H2Bub levels, to enhance ZEB1-mediated VEGFA transcription. USP22 depletion decreased cell proliferation, migration, Vascular Mimicry (VM) formation, and angiogenesis. Furthermore, we provided the evidence to show that knockdown of USP22 inhibited HCC growth in tumor-bearing nude mice. In addition, the expression of USP22 is positively correlated with that of ZEB1 in clinical HCC samples. Our findings suggest that USP22 participates in the promotion of HCC progression, if not all, at least partially via up-regulation of VEGFA transcription, providing a novel therapeutic target for anti-angiogenic drug resistance in HCC.

[Fluorescence spectroscopic characteristics of dissolved organic matters (DOM) from Jingpo Lake water].

Six samples (sample J1-J6) from Jingpo Lake in Heilongjiang province were analyzed by fluorescence and fluorescence excitation-emission matrix regional integration (FIR) to determine the different characteristics of dissolved organic matters (DOM). The results with the traditional method just analyzing the excitation, emission and synchronous fluorescence spectra indicated that DOM molecular condensation degree was highest at sample J4 and sample J5, however, the study with the three-dimensional-excitation emission matrix spectra (3EEMs) method showed that the content of protein-like material was higher in sample J6 than others. In the second method, 3EEMs was divided into five regions, among which Region I, Region II, and Region IV were related to protein-like material, Region II was related to fulvic acid-like material, Region V was related to humic acid-like organics, and then these regions were integrated named as A(I), A(II), A(III), A(IV) and A(V). The integration results showed that the volume of A(V) occupied the largest proportion of the DOM region integration from all samples, and it exhibited the most prominent both in sample J4 and sample J5, while it's opposite in sample J6. Integral ratio, which means humic acid-like region (A(III), A(V)) divided by protein-like region(A(I), A(II), A(IV)), showed that the value of J4(4. 94) was close to J5 (5.18), J1 (3.52) was close to J2 (3.66), and the minimum value appeared in J6 (2.11). From the above analysis, the DOM humification degree could be confirmed as follows: J4, J5 > J1, J2 > J3 > J6.

Pleasure of paying when using mobile payment: Evidence from EEG studies.

Mobile payment has emerged as a popular payment method in many countries. While much research has focused on the antecedents of mobile payment adoption, limited research has investigated the consequences of mobile payment usage relating to how it would influence consumer behaviors (e.g., purchase intention or willingness to pay). Here, we propose that mobile payment not just reduces the "pain of paying," a traditional view explaining why cashless payment stimulates spending, but it also evokes the "pleasure of paying," raising from the enhanced processing fluency in completing transactions. We tested this new conceptualization of "pleasure of paying" using EEG, complementing other behavioral measures. In two studies, we found that mobile payment effectively enhanced purchase likelihood (study 1, N = 66) and such an enhancement is generalizable to both hedonic and utilitarian products (study 2, N = 29). By employing EEG measures, we provided the first neural evidence of "pleasure of paying" in addition to the signal of "pain of paying." Critically, we demonstrated that the "pleasure of paying" is a distinctive psychological mechanism that is induced by mobile payment usage and that the "pleasure of paying" joins the "pain of paying" to mediate the increased purchase intention. We discuss the contributions and implications of these results to the ongoing evolution of cashless payment societies.

Restoration impacts on rates of denitrification and greenhouse gas fluxes from tropical coastal wetlands.

Forested coastal wetlands are globally important systems sequestering carbon and intercepting nitrogen pollution from nutrient-rich river systems. Coastal wetlands that have suffered extensive disturbance are the target of comprehensive restoration efforts. Accurate assessment of restoration success requires detailed mechanistic understanding of wetland soil biogeochemical functioning across restoration chrono-sequences, which remains poorly understood for these sparsely investigated systems. This study investigated denitrification and greenhouse gas fluxes in mangrove and Melaleuca forest soils of Vietnam, using the 15N-Gas flux method. Denitrification-derived N2O was significantly higher from Melaleuca than mangrove forest soils, despite higher potential rates of total denitrification in the mangrove forest soils (8.1 ng N g-1 h-1) than the Melaleuca soils (6.8 ng N g-1 h-1). Potential N2O and CO2 emissions were significantly higher from the Melaleuca soils than from the mangrove soils. Disturbance and subsequent recovery had no significant effect on N biogeochemistry except with respect to the denitrification product ratio in the mangrove sites, which was highest from the youngest mangrove site. Potential CO2 and CH4 fluxes were significantly affected by restoration in the mangrove soils. The lowest potential CO2 emissions were observed in the mid-age plantation and potential CH4 fluxes decreased in the older forests. The mangrove system, therefore, may remove excess N and improve water quality with low greenhouse gas emissions, whereas in Melaleucas, increased N2O and CO2 emissions also occur. These emissions are likely balanced by higher carbon stocks observed in the Melaleuca soils. These mechanistic insights highlight the importance of ecosystem restoration for pollution attenuation and reduction of greenhouse gas emissions from coastal wetlands. Restoration efforts should continue to focus on increasing wetland area and function, which will benefit local communities with improved water quality and potential for income generation under future carbon trading.

The effects of brand familiarity and product category in brand extension: An ERP study.

In this paper, neural features influenced by brand familiarity and category were investigated in a brand extension experiment by using conventional event-related potentials (ERPs) and time-frequency analysis. Twenty-four participants were required to decide whether to accept the extension of one brand (stimulus 1) to a certain product category (stimulus 2) in a 2 familiarity x 2 category paradigm. Stimulus 1 consisted of household appliance brands that had different degrees of familiarity (high familiarity vs. low familiarity) to a certain participant, and stimulus 2 consisted of two categories of products (high conflict vs. low conflict). Twenty-two sets of valid data were used for data analysis. We found greater N270 amplitudes in the low-familiarity brand condition and in the high-conflict product category condition, which meant that the participants had to devote more cognitive resources when the brand was less familiar and felt more conflict when the brand was extended to the high-conflict product category. According to the time-frequency analysis results, brand familiarity and product category were found to have a significant effect on the amplitude of theta-band power (4-7.5 Hz) at frontal electrodes in the time period of 270-340 ms. This result indicated that the activity of individual nodes of the language processing networks increased when the extension product category was mismatched with respect to the brand name and that the related memory of the brand was activated and the long-term memory was extracted when the participants faced the high-familiarity brand extension. The study provides an insightful view of how brand familiarity and category influence consumers' cognitive processes regarding brand extension.

A Novel Recurrent Neural Network to Classify EEG Signals for Customers' Decision-Making Behavior Prediction in Brand Extension Scenario.

It was meaningful to predict the customers' decision-making behavior in the field of market. However, due to individual differences and complex, non-linear natures of the electroencephalogram (EEG) signals, it was hard to classify the EEG signals and to predict customers' decisions by using traditional classification methods. To solve the aforementioned problems, a recurrent t-distributed stochastic neighbor embedding (t-SNE) neural network was proposed in current study to classify the EEG signals in the designed brand extension paradigm and to predict the participants' decisions (whether to accept the brand extension or not). The recurrent t-SNE neural network contained two steps. In the first step, t-SNE algorithm was performed to extract features from EEG signals. Second, a recurrent neural network with long short-term memory (LSTM) layer, fully connected layer, and SoftMax layer was established to train the features, classify the EEG signals, as well as predict the cognitive performance. The proposed network could give a good prediction with accuracy around 87%. Its superior in prediction accuracy as compared to a recurrent principal component analysis (PCA) network, a recurrent independent component correlation algorithm [independent component analysis (ICA)] network, a t-SNE support vector machine (SVM) network, a t-SNE back propagation (BP) neural network, a deep LSTM neural network, and a convolutional neural network were also demonstrated. Moreover, the performance of the proposed network with different activated channels were also investigated and compared. The results showed that the proposed network could make a relatively good prediction with only 16 channels. The proposed network would become a potentially useful tool to help a company in making marketing decisions and to help uncover the neural mechanisms behind individuals' decision-making behavior with low cost and high efficiency.

Does mobile payment change consumers' perception during payment process? -An ERP study.

Innovative payment methods have been getting worldwide attention. Exploring the mechanisms behind consumers' purchase behaviors modulated by different payment methods was critical but challenging. In this paper, we proposed a 2 (payment methods: cash payment vs mobile payment) × 2 (price levels of products: high vs low) Event-Related Potentials (ERPs) experiment to study the difference of cash payment and mobile payment on consumers' purchase intention of products in different price level from a neuroscience perspective. Greater P200 amplitude was found in mobile payment condition, which meant that mobile payment captured more early attention resources than cash. Larger N270 amplitude was found in cash payment condition as the participants had to spend more cognitive resources and struggled more when using cash. Moreover, lower N270 amplitude was found in high-price product condition, which indicated that when there were limited cognitive resources, the affective process played a dominating role. Specifically, buying the high-price products with mobile payment, the consumers would experience the pleasure of consumption more rather than the pain of paying. The study offers insights on the cognitive process of consumers when they pay with different methods.

PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells.

Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers.

Corrigendum: "You Win, You Buy"-How Continuous Win Effect Influence Consumers' Price Perception: An ERP Study.

[This corrects the article DOI: 10.3389/fnins.2018.00691.].

"You Win, You Buy"-How Continuous Win Effect Influence Consumers' Price Perception: An ERP Study.

Price played an important role in most purchases. Buying behavior was strongly determined by consumers' price expectations. Emotion as a research hotspot was demonstrated to be ubiquitous in marketing and influenced purchase processing as well. This study addressed interests upon whether emotion arousal would influence consumers' price perceptions and their willingness to purchase. Compared to such emotion researches which normally adopted emotional pictures as priming stimuli, we creatively employed a two-player "Finger Play" (FP) game without monetary gains or losses to arouse subjects' emotion in the experiment. A 2 (FP Game Results: Continuous Win vs. Continuous Lose) by 2 (Price Conditions: High Price vs. Low Price) Event-Related Potentials (ERPs) experiment was designed to investigate whether game results would arouse different emotions and influence subjects' perception of product price. Both behavioral and ERP results indicated that subjects' price perception was deeply impacted by emotions induced from continuous win/lose experiences.

Core-shell superparamagnetic Fe3O4@ß-CD composites for host-guest adsorption of polychlorinated biphenyls (PCBs).

The effective recognition and enrichment of trace polychlorinated biphenyls (PCBs) in the environment are currently challenging issues due to human health concerns. In this paper, a surface absorptive layer coating superparamagnetic Fe3O4 nanoparticles for PCBs enrichment were prepared. This protocol involved the synthesis of Fe3O4 particles through a solvothermal reaction and the covering of a silica layer bonded ß-cyclodextrin (ß-CD) over Fe3O4 via a sol-gel process to construct core-shell Fe3O4@ß-CD composites. ß-CD was linked covalently to Fe3O4 nanoparticles to generate the binding sites, enhancing the stability of Fe3O4 nanoparticles in water. Meanwhile, superparamagnetic Fe3O4 core could be rapidly separated from matrix to simplify time-consuming washing extraction. The adsorption capacity of Fe3O4@ß-CD composites to PCB28 and PCB52 in aqueous solutions was investigated. To estimate the theoretical binding site number of Fe3O4@ß-CD, the obtained binding data were replotted according to Scatchard equation. The host-guest interaction between ß-CD and PCBs were further examined with density functional theory (DFT) calculations. It provides theoretical evidence of ß-CD as host molecule has a higher binding amount towards PCB-28 than PCB-52 on the basis of their optimized geometries and calculated complexation energies. The nanomaterial reported herein is an ideal candidate for various applications, including the recognition and removal of environmentally deleterious substances.

Synthesis of mixed-chain phosphatidylcholines including coumarin fluorophores for FRET-based kinetic studies of phospholipase A(2) enzymes.

Phospholipase A2 (PLA2) enzymes catalyze the hydrolysis of the sn-2 ester linkage of glycerophospholipids to produce fatty acids and lysophospholipids. A significant number of mammalian phospholipases comprise a family of secreted PLA2 enzymes, found in specific tissues and cellular locations, exhibiting unique enzymatic properties and distinct biological functions. Development of new real-time spectrofluorimetric PLA2 assays should facilitate the kinetic characterization and mechanistic elucidation of the isozymes in vitro, with the potential applicability to detect and measure catalytic PLA2 activity in tissues and cellular locations. Here we report a new synthesis of double-labeled phosphatidylcholine analogs with chain-terminal reporter groups including coumarin fluorophores for fluorescence resonance energy transfer (FRET)-based kinetic studies of PLA2 enzymes. The use of coumarin derivatives as fluorescent labels provides reporter groups with substantially decreased size compared to the first generation of donor-acceptor pairs of fluorescent phospholipids. The key advantage of the design is to interfere less with the physicochemical properties of the acyl chains, thereby improving the substrate quality of the synthetic probes. In order to assess the impact of the fluorophore substituents on the catalytic hydrolysis and on the phospholipid packing in the lipid-water interface of the assay, we used the experimentally determined specific activity of bee-venom phospholipase A2 as a model for the secretory PLA2 enzymes. Specifically, the rate of PLA2 hydrolysis of the coumarin labeled phosphatidylcholine analogs was less than three times slower than the natural substrate dipalmitoyl phosphatidylcholine (DPPC) under the same experimental conditions. Furthermore, variation of the mole fraction of the synthetic phosphatidylcholine vs. that of the natural DPPC substrate showed nearly ideal mixing behavior in the phospholipid-surfactant aggregates of the assay. The synthesis provides a rapid and efficient method for preparation of new synthetic phosphatidylcholines with the desired target structures for enzymatic and physicochemical studies.