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An iodine-catalyzed methyl azaarene sp3 C–H functionalization has been developed for the synthesis of pyrazolooxepinopyrazolones. This method has wide range of substrates, low catalyst loading, good functional group tolerance and metal-free conditions.

Maceration is fundamental to producing high quality red wine through the extraction of components from grape, including pigments of importance to wine colour. The effects of copigments and commonly used winemaking additives (maceration enzyme, SO2) on the extraction of malvidin-3-O-glucoside (M3G) were modelled under simulated maceration conditions. Copigments (gallic acid, rutin, caffeic acid) did not significantly facilitate the mass transfer process of M3G nor colour extraction, with caffeic acid having significantly lower values. Importantly, SO2 showed the most positive effects on both mass distribution constant and internal mass transfer coefficient of M3G, with temperature and ethanol having less of an impact. Significant interactions of the experimental factors were observed, however, and SO2, temperature, and ethanol were found to play predominant roles in the extraction phenomena. Comparatively, maceration enzyme or rutin (most impactful copigment) did not exhibit as much of an influence on the mass transfer process of M3G.

Malvidin-3-O-(6-O-acetyl)-glucoside is usually the most abundant acylated anthocyanin in red wines. In this work, intermolecular copigmentation of malvidin-3-O-(6-O-acetyl)-glucoside and malvidin-3-O-glucoside with three phenolic copigments was carried out in model wine solutions, and the influence of the acetylation group was evaluated emphatically using experimental and theoretical approaches. This study found that there was no distinct coloring difference in the two anthocyanins themselves; however, the hyperchromic effects were smaller in malvidin-3-O-(6-O-acetyl)-glucoside solutions with the existence of insufficient copigments. Thermodynamic analysis confirmed that malvidin-3-O-(6-O-acetyl)-glucoside showed weaker affinity (smaller K values) toward the three copigments compared with its non-acylated form. Theoretical analysis also indicated that the existence of the acetylation group changed the spatial conformations and non-covalent interactions (hydrogen bonds and van der Waals forces) of the copigmentation complexes, which might be due to the potential steric hindrance effect. In conclusion, the results revealed that the acetylation group on anthocyanin glycosyl could impede intermolecular copigmentation.

Crosstalk between pyroptosis and tumor immune microenvironment (TIME) in cancer has yet to be elucidated. Herein, we aimed to explore the role of pyroptosis and its association with TIME in gastric cancer. Unsupervised clustering was performed to identify the pyroptosis-related clusters. Pyroptosis risk score was constructed using LASSO Cox regression. Clinicopathological and genetic data of pyroptosis clusters and pyroptosis risk scores were explored. Reproducibility of pyroptosis risk score in predicting response to immunotherapy and screening potential antitumor drugs was also investigated. Three pyroptosis clusters with distinct prognosis, immune cell fractions and signatures, were constructed. A low-pyroptosis risk score was characterized by increased activated T-cell subtype and M1 macrophage, decreased M2 macrophage, higher MSI status, and TMB. Meanwhile, low-score significantly correlated with PD-L1 expression, antigen presentation markers, and IFN-γ signature. The 5-year AUCs of PRS were 0.67, 0.62, 0.65, 0.67, and 0.67 in the TCGA, three external public and one real-world validation (SYSUCC) cohorts. Multivariable analyses further validated the prognostic performance of the pyroptosis risk scoring system, with HRs of 2.43, 1.83, 1.78, 2.35, and 2.67 (all p < 0.05) in the five cohorts. GSEA indicated significant enrichment of DNA damage repair pathways in the low-score group. Finally, the pyroptosis risk scoring system was demonstrated to be useful in predicting response to immunotherapy, and in screening potential antitumor drugs. Our study highlights the crucial role of interaction between pyroptosis and TIME in gastric cancer. The pyroptosis risk scoring system can be used independently to predict the survival of individuals and their response to immunotherapy.

Color is one of the most distinctive qualities of red wine. Despite new knowledge in the field of pigment identification, copigmentation, and oxidation being forthcoming, there is still a large gap between the fundamental research and practical winemaking outcomes. A state-of-art review from these two aspects is, therefore, necessary. This review first introduces updated knowledge about the primary pigments in wine, with emphasis on their physicochemical properties. Then, the mechanisms of copigmentation and oxidation are elucidated in detail, along with their relative contributions to wine color. Finally, the practical effects of copigmentation and micro-oxygenation (MOX) in winemaking are summarized and discussed. In general, wine coloration is ultimately determined by the anthocyanin flavylium cation, which is greatly influenced by wine pH. In young red wine, grape-derived anthocyanins and nonanthocyanin polyphenols (as copigments) are the foundation for wine coloration. During aging and storage, anthocyanin derivatives are formed via various chemical reactions, where moderate oxidation plays a vital role, whereas copigmentation constantly decreases. The essence of wine color evolution relates to the changes of physicochemical properties of primary pigments in wine, where the hydration equilibrium gradually diminishes. In practice, the effects of copigment addition and MOX during real vinification can be viewed as somewhat controversial, considering that many studies showed different effects on wine color and pigment concentration. Universal features can be summarized but some phenomena still remain unclear and deserve further exploration.

The “macrotrabecular-massive” (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients. Electronic supplementary material The online version of this article (10.1007/s00262-020-02691-9) contains supplementary material, which is available to authorized users.

The aldo‐keto reductases family 1 member C2 (AKR1C2) has critical roles in the tumorigenesis and progression of malignant tumours. However, it was also discovered to have ambiguous functions in multiple cancers and till present, its clinical significance and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) has been unclear. The aim of this study was to explore the role of AKR1C2 in the tumorigenesis of ESCC. Here, we showed that AKR1C2 expression was found to be up‐regulated in ESCC tissues and was significantly associated with pathological stage, lymph node metastasis and worse outcomes. Functional assays demonstrated that an ectopic expression of AKR1C2 in ESCC cells resulted in increased proliferation, migration and cisplatin resistance, while knockdown led to inversing effects. Bioinformation analyses and mechanistic studies demonstrated that AKR1C2 activated the PI3K/AKT signalling pathway, furthermore, the inhibitor of PI3K or the selective inhibitor of AKR1C2 enzyme activity could reverse the aggressiveness and showed synergistic antitumour effect when combined with cisplatin, both in vitro and in vivo. In conclusion, Our findings revealed that AKR1C2 could function as an oncogene by activating the PI3K/AKT pathway, as a novel prognostic biomarker and/or as a potential therapeutic target to ESCC.

As one of the most promising wine regions in China, the eastern foothills of the Helan Mountain (EFHM) in the Ningxia Hui Autonomous Region has attracted great attention recently. Geographically, EFHM is divided into six sub-regions, namely Shizuishan, Xixia, Helan, Qingtongxia, Yongning and Hongsipu. However, there have been few reports on the character and differences between wines in the six sub-regions. In this experiment, a total of 71 commercial Cabernet Sauvignon wines from six sub-regions were collected, and their phenolic compounds, visual properties and mouthfeel were investigated. The results showed that wines from the six sub-regions of EFHM showed distinctive phenolic profiles and could be distinguished through the OPLS-DA mode using 32 potential markers. In terms of color, Shizuishan wines showed higher a* values and lower b* values. The sensory evaluation showed that Hongsipu wines had higher astringency strength and lower tannin texture. The overall results implied that the phenolic compounds of wines in different sub-regions were affected by terroir conditions. To the best of our knowledge, this is the first time that a wide coverage of phenolic compounds has been analysed for wines from the sub-regions of EFHM, which could provide valuable information in deciphering the terroir of EFHM.

Wine quality is closely related to various compounds including polysaccharides, a class of crucial macromolecules that affect its chemical and physical properties by influencing the colloidal state or interacting with other compounds via non-covalent bonds. Herein, the composition and structural characteristics of the major polysaccharides identified in wine and the factors influencing their contents are briefly described. An improved understanding of the molecular mechanisms of wine polysaccharides and their practical applications on wine stability and organoleptic qualities is thoroughly discussed. The effects of polysaccharides on wine quality are significantly correlated with their structure and composition as well as wine matrix composition. Thus, to better understand the chemical complexity of polysaccharides, relevant analytical methods are systematically summarized and highlighted, which may ultimately lead to the development of novel winery guidelines.

An iodine-catalyzed methyl azaarene sp

Simple Summary Penile squamous cell carcinoma (PSCC) has been regarded as an HPV-related cancer for a long time. However, the integration pattern and carcinogenic pathways of HPV in PSCC remain unclear. The results of this study provide insights into the HPV-related carcinogenic mechanism in PSCC, which may be less prone to involvement in the traditional E6/E7 carcinogenic process, and are characterized by effects on the host genome, which result in the inactivation of tumor suppressors (CADM2, etc.) and the activation of oncogenes (KLF5, etc.), thus activating oncogenic signaling pathways (MAPK, JAK/STAT, etc.). This study could enhance our understanding of HPV integration and pave the way for subsequent HPV studies in PSCC. Abstract Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways.

The mechanical properties of artificial skins are complicated to maintain under ensuring air permeability and antimicrobial. Thus, a series of hydrophilic antimicrobial polymer networks are prepared by crosslinking chitosan and polyvinyl alcohol with the lauramidopropyl betaine and hydrogen bond organic framework (CS/PVA/LPB/2D-HOF). The mechanical performance of the control groups and the complex are systematically evaluated to attain an artificial strength skin. The CS/PVA/LPB/2D-HOF complex exhibits strong mechanical abilities than other control groups. By analyzing the IR spectra and the morphology, the synergistic effect of hydrogen bonds between molecules and cracks significantly improves the mechanical properties of the complex. Its maximum tensile strength can reach 29 MPa, and its maximum load capacity can reach 3700 g. Notably, the composite membrane also performs an excellent antimicrobial activity. In vivo and in vitro experiments show that the hybrid membrane can promote tissue regeneration and wound healing (95％). These results may open up the opportunity for future composite material investigations in the artificial skin and tissue engineering field.

Co3O4 nanostructures have been extensively studied as anode materials for rechargeable lithium-ion batteries (LIBs) because of their stability and high energy density. However, several drawbacks including low electrical transport and severe volume changes over a long period of operation have limited their utilities in LIBs. Rational composite design is becoming an attractive strategy to improve the performance and stability of potential lithium-ion-battery anode materials. Here, a simple method for synthesizing hollow Co3O4@TiO2 nanostructures using metal–organic frameworks as sacrificial templates is reported. Being used as an anode material for LIBs, the resulting composite exhibits remarkable cycling performance (1057 mAh g–1 at 100 mA g–1 after 100 cycles) and good rate performance. The optimized amorphous Co3O4@TiO2 hollow dodecahedron shows a significant improvement in electrochemical performance and shows a wide prospect as an advanced anode material for LIBs in the future.

The reaction kinetics of five primary wine anthocyanins (cyanidin-3-O-glucoside, peonidin-3-O-glucoside, delphinidin-3-O-glucoside, petunidin-3-O-glucoside, and malvidin-3-O-glucoside) and (−)-epicatechin with the presence of acetaldehyde were evaluated in model wine solutions at a range of varying temperatures (25, 35, 45, and 55 °C). The loss of anthocyanins followed first-order reaction model, while the formation of two isomers of anthocyanin ethyl-linked (−)-epicatechin was fitted to zero-order reaction model. The rate constant (k) showed that petunidin-3-O-glucoside was the most reactive anthocyanin, followed by the two 3′,4′-substituted anthocyanins (peonidin-3-O-glucoside and cyanidin-3-O-glucoside), while the least reactive were another two 3′,4′,5′-substituted anthocyanins (malvidin-3-O-glucoside and delphindin-3-O-glucoside). The activation energies (Ea) indicated that the formation of ethyl-linked products from methylated anthocyanins were more sensitive to temperature than that from hydroxylated anthocyanins. Thermodynamic parameters showed a non-spontaneous and endothermic process. Besides, the evolution of the visible color of reaction solution was affected by the stability of anthocyanins and the formation of ethyl-linked products.

Glycosidic aroma compounds are the important precursors of volatile aroma in grapes, and they can be added with odorous aglycones via enzyme- or acid-catalyzed hydrolysis during wine fermentation and storage. Developing an analytical method for intact glycosides can provide the possibility to study the accumulation of these aroma precursors in grape berries. For this purpose, a Tandem Mass Spectrometry (MS/MS). database based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry was built, covering multiple aglycone classes. Subsequently, the profiles of glycosidic aroma compounds in Vitis vinifera L. cv. Muscat Blanc, Riesling, and Chardonnay berries during maturation were investigated. Pentosyl-hexosides were the most abundant glycosides in all three varieties. Both composition and concentration of glycosidic aroma compounds varied obviously among grape varieties. Except for monoterpenol pentosyl-hexosides, most glycosides were kept almost stable in their concentrations during berry maturation. This research provides an approach to understand the variation of glycosidic aroma components from the perspective of aglycones and glycosides.

Glycosidic aroma compounds are the important precursors of volatile aroma in grapes, and they can be added with odorous aglycones via enzyme- or acid-catalyzed hydrolysis during wine fermentation and storage. Developing an analytical method for intact glycosides can provide the possibility to study the accumulation of these aroma precursors in grape berries. For this purpose, a Tandem Mass Spectrometry (MS/MS). database based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry was built, covering multiple aglycone classes. Subsequently, the profiles of glycosidic aroma compounds in Vitis vinifera L. cv. Muscat Blanc, Riesling, and Chardonnay berries during maturation were investigated. Pentosyl-hexosides were the most abundant glycosides in all three varieties. Both composition and concentration of glycosidic aroma compounds varied obviously among grape varieties. Except for monoterpenol pentosyl-hexosides, most glycosides were kept almost stable in their concentrations during berry maturation. This research provides an approach to understand the variation of glycosidic aroma components from the perspective of aglycones and glycosides.

Pinotin A is a crucial pyranoanthocyanin in aged red wine. The formation mechanism of pinotin A was investigated through experimental and theoretical approaches in model wine solution. Using UHPLC-DAD-QTOF, three intermediates were identified in the reaction solution of malvidin-3-O-glucoside and caffeic acid. The pH and oxidative conditions affected the reaction rate by modulating the accumulation of intermediates. Upon preparative HPLC and oxidation experiment, the transformation of intermediate 3 to intermediate 2 was observed through free radical oxidation, p-benzoquinone oxidation and autooxidation. However, the production of pinotin A was only achieved through autooxidation. A three-steps reaction mechanism of reversible addition reaction and decarboxylation, and autooxidation was proposed. The validity of the proposed mechanism was verified through quantum chemistry calculation. The negative variation of Gibbs free energy of the entire reaction was obtained, where the autooxidation step played a crucial role for the spontaneity of the whole reaction.

As a subseries of the covalent organic framework (COF) material family, polyimide-based covalent organic framework (PI-COF) material, which has the advantages of high stability of polyimide, high specific surface area, and controllable pores of COF material, is expected to be a new type of porous material with potential applications. Although the development of PI-COF is in the early stages during the past decade, it has attracted extensive attention and is widely used in heterogeneous catalysis, gas separation, and storage fields. Therefore, this review is aiming to give a comprehensive understanding of the recent progress of PI-COFs. This article summarizes the progress of PI-COF from three aspects: controllable structure design, synthesis method, and application. First of all, under the guidance of network chemical design principles, the topology type of PI-COF and the size and shape of the formed pores are summarized in terms of different organic monomers. Then the five synthetic strategies for the synthesis of PI-COF are analyzed. Finally, the applications of PI-COF in adsorption and separation, drug delivery, solar-to-electrochemical energy storage, photocatalysis, and electrocatalyst are introduced.

Anthocyanin derivatives and chromatic characteristics of 234 different-vintage red wine were investigated based on a targeted HPLC-MS/MS and CIELAB approach. The K-means cluster analysis showed that the evolution pattern varies amongst anthocyanin derivative classes. Their stabilities are: pinotins > flavanyl-pyranoanthocyanins, vitisin A > monomeric anthocyanin, direct anthocyanin-flavan-3-ols condensation products > vitisin B, anthocyanin ethyl-linked flavan-3-ols products. The proportion of most pyranoanthocyanins becomes more significant among all detected anthocyanin derivatives during wine aging, whereas flavanols-related anthocyanin derivatives (except for flavanyl-pyranoanthocyanins) decreased drastically. PLSR showed that aging tawny characteristics is related to pyranoanthocyanins except for vitisin B, especially pinotins, whereas monomeric anthocyanins and flavanol-related derivates (except for flavanyl-pyranoanthocyanins) contribute to red violet color. But aging color density is more associated with the content of vitisin A and flavanyl-pyranoanthocyanins. Two predictive models based on random forest and support vector machine modeling showed good performance in predicting the extent of wine aging.

Phenolic copigments have important influence on red wine color. In this study, UV-visible spectrophotometer and UHPLC-Q-TOF-MS were combined to investigate the effects of three types of phenolic copigments (gallic acid, (-)-epicatechin, and quercetin-3-O-glucoside) on the stability and color properties of five common 3-O-monoglucosidic anthocyanins in model wine solutions. Results showed low concentrations (0.5 mM) of gallic acid and (-)-epicatechin protected anthocyanins from degradation, whereas high concentrations (8 mM) of them had the opposite effect. Quercetin-3-O-glucoside always improved the stability of anthocyanins despite its additive amount (0.1 mM or 0.4 mM). Even small quantity of (-)-epicatechin led to obvious yellow hue into the solution, and xanthylium derivatives generated from (-)-epicatechin were detected. Antagonistic effect among the three copigments was observed, probably as a result of competition of intermolecular copigmentation. Additionally, the stability of anthocyanins was significantly influenced by their structures: cyanidin-3-O-glucoside, peonidin-3-O-glucoside, and malvidin-3-O-glucoside were more stable than delphinidin-3-O-glucoside and petunidin-3-O-glucoside.

Coil-to-globule transitions are fundamental problems existing in polymer science for several decades; however, some features are still unclear, such as the effect of chain monomer interaction. Herein, we use Monte Carlo simulation to study the coil-to-globule transition of simple compact polymer chains. We first consider the finite-size effects for a given monomer interaction, where the short chain exhibits a one-step collapse while long chains demonstrate a two-step collapse, indicated by the specific heat. More interestingly, with the decrease of chain monomer interaction, the critical temperatures marked by the peaks of heat capacity shift to low values. A closer examination from the energy, mean-squared radius of gyration and shape factor also suggests the lower temperature of coil-to-globule transition.

Though non-anthocyanin phenolics normally do not have red color, they affect the red color expression in the copigmentation of red wines. In this study, the influence of prefermentative addition of 300 mg/L gallic acid and ellagic acid, as cofactors, on aging dry red wines had been systematically evaluated at the industrial scales from the perspectives of color, phenolic profiles and copigmentation effects of anthocyanins. Red wines made with these two compounds exhibited better color properties than the control, having better CIELAB chromatic parameters. Additionally, significantly higher levels of detectable anthocyanins and copigmented anthocyanin ratio had been observed. Wines with ellagic acid showed better chromatic properties and phenolic profiles than wines with gallic acid, as shown in previous theoretical results. Anti-copigmentation phenomenon was noticed and elucidated. These practical results confirmed that ellagic acid was the better cofactor, and would give more additional guidance for the production of high quality wine. Chemical compounds Malvidin-3-O-glucoside (PubChem CID: 443,652); Petunidin-3-O-glucoside (PubChem CID: 443,651); Delphinidin-3-O-glucoside (PubChem CID: 443,650); Peonidin-3-O-glucoside (PubChem CID: 443,654); Ellagic acid (PubChem CID: 5,281,855); Gallic acid (PubChem CID: 370); Quercetin (PubChem CID: 443,654); Caffeic acid (PubChem CID: 689,043); (+)-catechin (PubChem CID: 9064); Vanillic acid (PubChem CID: 8468).

Background: Monosaccharides, organic acids and amino acids are the important flavour-related components in wines. The aim of this article is to develop and validate a method that could simultaneously analyse these compounds in wine based on silylation derivatisation and gas chromatography-mass spectrometry (GC-MS), and apply this method to the investigation of the changes of these compounds and speculate upon their related influences on Cabernet Sauvignon wine flavour during wine ageing. This work presented a new approach for wine analysis and provided more information concerning red wine ageing.; Results: This method could simultaneously quantitatively analyse 2 monosaccharides, 8 organic acids and 13 amino acids in wine. A validation experiment showed good linearity, sensitivity, reproducibility and recovery. Multiple derivatives of five amino acids have been found but their effects on quantitative analysis were negligible, except for methionine. The evolution pattern of each category was different, and we speculated that the corresponding mechanisms involving microorganism activities, physical interactions and chemical reactions had a great correlation with red wine flavours during ageing.; Conclusion: Simultaneously quantitative analysis of monosaccharides, organic acids and amino acids in wine was feasible and reliable and this method has extensive application prospects. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.

Anthocyanin derivatives are critical components that impart color to aging red wine. In this study, we developed a targeted metabolomic method for the simultaneously profiling of the primary thirty-seven malvidin-derived anthocyanin derivatives in red wine, including various pyranoanthocyanins and flavanols-related condensation products. First, high-performance liquid chromatography (HPLC) tandem ion trap and triple-quadrupole (QqQ) mass spectrometry were used to construct the mass spectral and chromatographic database of the anthocyanin derivatives that were formed in a model wine solution. Next, the targeted profiling analysis of these compounds was achieved on a QqQ mass spectrometer in the multiple reaction monitoring mode (MRM). The method displayed excellent linearity (R2 0.9391–0.9998), sensitivity (0.221–0.604 μg/L of limit of detection (LOD) and 0.274–1.157 μg/L of limit of quantification (LOQ) equivalent to malvidin-3-O-glucoside (Mv-glc)), and repeatability (less than 10% and 15% for intra-day and inter-day relative standard deviation (RSD) respectively). Partial least squares discriminant analysis (PLS-DA) based on this method showed great discrimination over different vintage wines, thereby promising to be an effective tool in wine anthocyanin and aging related study.

Background With the rapid development of the high throughput detection techniques, tumor-related Omics data has become an important source for studying the mechanism of tumor progression including breast cancer, one of the major malignancies worldwide. A previous study has shown that the G2 and S phase-expressed-1 (GTSE1) can act as an oncogene in several human cancers. However, its functional roles in breast cancer remain elusive. Method In this study, we analyzed breast cancer data downloaded from The Cancer Genome Atlas (TCGA) databases and other online database including the Oncomine, bc-GenExMiner and PROGgeneV2 database to identify the molecules contributing to the progression of breast cancer. The GTSE1 expression levels were investigated using qRT-PCR, immunoblotting and IHC. The biological function of GTSE1 in the growth, migration and invasion of breast cancer was examined in MDA-MB-231, MDA-MB-468 and MCF7 cell lines. The in vitro cell proliferative, migratory and invasive abilities were evaluated by MTS, colony formation and transwell assay, respectively. The role of GTSE1 in the growth and metastasis of breast cancer were revealed by in vivo investigation using BALB/c nude mice. Results We showed that the expression level of GTSE1 was upregulated in breast cancer specimens and cell lines, especially in triple negative breast cancer (TNBC) and p53 mutated breast cancer cell lines. Importantly, high GTSE1 expression was positively correlated with histological grade and poor survival. We demonstrated that GTSE1 could promote breast cancer cell growth by activating the AKT pathway and enhance metastasis by regulating the Epithelial-Mesenchymal transition (EMT) pathway. Furthermore, it could cause multidrug resistance in breast cancer cells. Interestingly, we found that GTSE1 could regulate the p53 function to alter the cell cycle distribution dependent on the mutation state of p53. Conclusion Our results reveal that GTSE1 played a key role in the progression of breast cancer, indicating that GTSE1 could serve as a novel biomarker to aid in the assessment of the prognosis of breast cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1157-4) contains supplementary material, which is available to authorized users.

Developing new visible light-triggered fluorescent molecular photoswitches is highly desirable for potential application in the fields of photoresponsive optoelectronics and photopharmacology. In this contribution, two novel tetra-/triphenylethene-dithienylethene-BF2bdk triads (TDB1 and TDB2) have been designed and prepared by appending tetra-/triphenylethene and BF2bdk moieties at the termini of dithienylethene unit. Before irradiation with blue light at 460-470 nm, they showed an intense emission in solution and in the PMMA film state, suggesting that the AIE effect of tetra-/triphenylethene was inhibited, and functioned only as electron-donating groups. Moreover, upon alternating irradiation with blue/NIR light, TDB1 and TDB2 displayed effective fluorescent switching behaviors and NIR photochromism in toluene and the PMMA film. Therefore, they would be utilized as novel visible light-triggered switches integrated in smart optoelectronic materials. The DFT calculations further validate the differences for their optical properties in the experiments.

Due to the relatively excellent chemical and hydrothermal stability as well as structural stability, UiO-type PCPs exhibit good adaptability in the humid and acid atmosphere. Considering that, we anchored this type of materials to study their structural properties and adsorption behavior. Concretely, we have synthesized UiOs with different pore diameters by employing different length organic ligand and prepared magnetic functional Fe3O4@UiOs by encapsulation. In this paper, we have studied the adsorption behavior of four UiO-type PCPs on AO7, and the optimum adsorption amount of UiO-67 on acid orange 7 achieving 250 mg/g. The adsorption mechanism was then discussed in detail by combining the porosity and the Zeta potential analysis. When the PCPs are mainly mesoporous, the adsorption manner fits physical adsorption, while microporous is in accordance with chemisorption. The adsorption capacity of the materials can be improved by designing the porosity in the molecule level, and a larger porosity ensures a stronger adsorption capacity. The results identified that this strategy was a promising solution to produce UiO-type PCPs based adsorbents with excellent adsorption performance for effective removal of toxic chemicals from wastewater and industrial sustainability, medical processes, and environment-related areas.

Figure S5. (A) Pattern of β-Galactosidase staining in the indicated cell. (B) The data are presented as the mean ± S.D. **p

Table S1: Primer sequence. Table S2: The sequences of small interfering RNA of GTSE1. Table S3: GTSE1 â SureSilencing shRNAâ plasmids sequences. (DOCX 27 kb)

Figure S2. (A and B) Plate clone formation assays were conducted in the indicated cells. The data are presented in triplicates as the meanâ Âąâ S.D. (PDF 4660 kb)

Figure S1. (A, B and C) OS, RFS and DMFS K-M curve for breast cancer patients with either GTSE1 high or GTSE1 low mRNA expression based on PROGgeneV2 database. (PDF 1460 kb)

Figure S3. (A) Overexpression of GTSE1 could promote cell migration in MCF7 cells compared with control cells. (B and C) Silencing or overexpression of GTSE1 markedly changed cell migration as detected by wound-healing assay. (D and E) Quantification data for C and D. *p

Figure S4. (A and B) The gating of MDA-MB-231 siNC and siGTSE1 group cells were treated with 5-fluorouracil (5μg/ml) for 48 h and test for apoptosis respectively. (C and D) The gating of MDA-MB-468 siNC and siGTSE1 group cells were treated with 5-fluorouracil (0.9μg/ml) for 48 h and test for apoptosis respectively. (E and F) The gating of MDA-MB-231-vector and overexpression of GTSE1 group cells were treated with 5-fluorouracil (5μg/ml) for 48 h, then test its apoptosis rate respectively. (G and H) The gating of MCF7-vector and overexpression of GTSE1 group cells were treated with 5-fluorouracil (20μg/ml) for 48 h, then test its apoptosis rate respectively. (PDF 3207 kb)

Grape (Vitis vinifera L.) pomace, the residue of red wine production, is a good source material for production of anthocyanins. In this study, an effective and simple method for semi-preparative isolation of anthocyanins from grape pomace was developed. Ultrasonication with acidified MeOH was used to extract anthocyanins, with 56.15 mg total anthocyanins being obtained from 50 g grape pomace. Crude extracts were purified by XAD-7HP column chromatography, followed by isolation of the anthocyanin mixtures using semi-preparative HPLC, and subsequent identification of anthocyanin monomers by HPLC-DAD-MS/MS. Fourteen anthocyanins were isolated with high purities (≥90%), among which were non-acylated and acylated anthocyanins, and their cis and trans isomers. It is believed this is the first time that nearly all primary anthocyanin monomers in grapes have been isolated simultaneously using a single-step semi-HPLC procedure. The findings of this study will contribute to further research on anthocyanin monomers and profitable utilization of grape pomace.

Sambutoxin, a representative derivative of 4-hydroxy-2-pyridone, was isolated from Hericium alpestre for the first time in this study. The possible correlation between the sambutoxin-induced suppression of tumor growth and its influence on cell-cycle arrest and apoptosis was investigated. The effects of sambutoxin on reactive oxygen species (ROS) production, DNA damage, mitochondrial transmembrane potential, cell apoptosis, and the expression of related proteins were evaluated. An in vitro cell viability study demonstrated that sambutoxin could inhibit the proliferation of various cancer cells. Treatment with sambutoxin induced the production of ROS, which caused DNA damage. Furthermore, the subsequent sambutoxin-induced activation of ATM and Chk2 resulted in G2/M arrest, accompanied by decreased expression of cdc25C, cdc2, and cyclin B1. Sambutoxin induced apoptosis by activating the mitochondrial apoptosis pathway through an increased Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (ΔΨm), cytochrome (Cyt) c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) degradation. The ROS elevation induced the sustained phosphorylation of c-Jun N-terminal kinase (JNK), while SP600125, a JNK inhibitor, nearly completely reversed sambutoxin-induced apoptosis. Accordingly, an in vivo study showed that sambutoxin exhibited potential antitumor activity in a BALB/c nude mouse xenograft model without significant systemic toxicity. Moreover, the expression changes in proteins related to the G2/M phase, DNA damage, and apoptosis in vivo were consistent with those in vitro. Importantly, sambutoxin has remarkable antiproliferative effects and is a promising anticarcinogen candidate for cancer treatment.

Programmed cell death-ligand 1(PD-L1) was expressed in various malignancies, and interaction with its receptor programmed cell death 1 (PD-1) often contributed to immune evasion of tumor cells. In this study, we explored the expression of PD-L1 and its correlation with clinical outcomes in gliomas. Clinicopathological data of 229 patients with gliomas was collected. PD-L1 expression was assessed by tissue-microarray-based immunohistochemistry. Over 5% of tumor cells with cytoplasm or membrane staining was defined as PD-L1 positive expression. The associations of clinicopathological features with overall survival (OS) and disease-free survival (DFS) were analyzed by univariate analysis and multivariate analysis was further performed by Cox regression model. PD-L1 positive expression was observed in 51.1% gliomas patients and no significant association was verified between PD-L1 expression and pathological grade in 229 gliomas patients. However, PD-L1 expression rate was 49.2%, 53.7% and 68.8% for grade II, III and IV in 161 patients with those ≥ 12 months of OS, respectively. Although no significant discrepancies was displayed, there was a certain degree of differences between PD-L1 expression and pathological grade (49.2% vs. 53.7% vs. 68.8%, P = 0.327). Univariate analysis showed that PD-L1 expression was significantly associated with poor OS in the patients with long-time survival or follow up (OS ≥ 12 months) (P = 0.018), especially in patients with grade IV (P = 0.019). Multivariate analysis revealed that a strong tendency towards statistical significance was found between PD-L1 expression and poor OS (P = 0.081). In gliomas patients with long-time survival or follow up, PD-L1 positive expression could indicate the poor prognosis and it is possible that immunotherapy targeting PD-L1 pathway needed to be determined in the further study.

OBJECTIVE Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. RESULTS Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). CONCLUSIONS Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

// Tao Qin 1,* , Yin-duo Zeng 1,2,* , Ge Qin 1,* , Fei Xu 1,* , Jia-bin Lu 1 , Wen-feng Fang 1 , Cong Xue 1 , Jian-hua Zhan 1 , Xin-ke Zhang 1 , Qiu-fan Zheng 1 , Rou-jun Peng 1 , Zhong-yu Yuan 1 , Li Zhang 1 and Shu-sen Wang 1 1 Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 2 Sun Yat-sen University Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China * These authors have contributed equally to this work Correspondence to: Shu-sen Wang, email: // Li Zhang, email: // Zhong-yu Yuan, email: // Keywords : PD-L1, breast cancer, ER, PR, prognosis, nomogram Received : July 07, 2015 Accepted : August 22, 2015 Published : September 10, 2015 Abstract Background: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer. Methods: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression. Results: The median follow-up time was 98 months(range, 17–265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis. Conclusions: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.

Mg-Al layered double hydroxide (LDH) was modified with sodium dodecyl sulfate (SDS) by regeneration method. The structure of modified LDH (SDS-LDH) was investigated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The composites of SDS-LDH and polyethylene (PE) were prepared by melt blending and solution mixing method with maleated PE (PEgMA) as compatibilizer. The structure of the composites and the dispersion of SDS-LDH in the matrix were investigated by XRD and transmission electron microscopy (TEM), respectively. The results reveal that SDS was successfully intercalated into the interlayer space of LDH. SDS-LDH was hardly exfoliated in PE/PEgMA by melt blending. The nanocomposites of PE/(PEgMA/SDS-LDH) were successfully prepared by melt blending PE with SDS-LDH/PEgMA master-batch obtained by solution mixing. Homogeneous dispersion of SDS-LDH in the matrix was observed by TEM.

On the one hand, the opening up of the trading ports in the late 19th century has blocked the way of independent development of national capitalism, but on the other hand, it also exploited a vast market for the development of national capitalism, and promoted its own development. Zhejiang silk traders took this opportunity to go abroad for accepting foreign cultures and new ideas which were also reflected on the architectures. Their residences have broken the styles of the Chinese traditional architectures which are made of wood, stone, pantile, etc. and blended the western architectural culture elements in the roof form and facade material of the buildings. With Chinese style outside and western style inside, with elegance outside and dominance inside, the residences mainly make a perfect combination of Chinese pattern and western pattern. Based on the political, economic and social climate of the time, this article seeks the design features and aesthetic taste of Chinese and Western architectures.

Monosaccharides, organic acids and amino acids are the important flavour-related components in wines. The aim of this article is to develop and validate a method that could simultaneously analyse these compounds in wine based on silylation derivatisation and gas chromatography-mass spectrometry (GC-MS), and apply this method to the investigation of the changes of these compounds and speculate upon their related influences on Cabernet Sauvignon wine flavour during wine ageing. This work presented a new approach for wine analysis and provided more information concerning red wine ageing.This method could simultaneously quantitatively analyse 2 monosaccharides, 8 organic acids and 13 amino acids in wine. A validation experiment showed good linearity, sensitivity, reproducibility and recovery. Multiple derivatives of five amino acids have been found but their effects on quantitative analysis were negligible, except for methionine. The evolution pattern of each category was different, and we speculated that the corresponding mechanisms involving microorganism activities, physical interactions and chemical reactions had a great correlation with red wine flavours during ageing.Simultaneously quantitative analysis of monosaccharides, organic acids and amino acids in wine was feasible and reliable and this method has extensive application prospects. © 2017 Society of Chemical Industry.

The aim of this study was to analyze the imaging findings of 15 cases of malignant fibrous histiocytoma (MFH) of the head and neck, in order to better understand the tumor characteristics based on computed tomography (CT) and magnetic resonance imaging (MRI). CT (n=11) and MRI (n=4) images from 15 patients with histologically diagnosed MFH of the head and neck were retrospectively analyzed. The imaging characteristics were analyzed and compared among different histological subtypes. The lesions were primarily located in the maxillary sinus in 5 patients, the ethmoid sinus in 1 patient, the infratemporal fossa in 2 patients, the neck in 4 patients, the left mandible in 1 patient, the gingiva in 1 patient and the epiglottis in 1 patient. A total of 4 cases were associated with radiotherapy. All the lesions were ill-defined, ranging in size from 2.1 to 5.1 cm in the largest diameter. Bone fractures were evident in 9 cases. The attenuation, signal and enhancement patterns varied, although inflammatory MFH exhibited prolonged enhancement in dual-phase enhanced CT scans. MFH of the head and neck is rare but may be associated with radiotherapy. Although the imaging manifestations of MFH are various and non-specific, inflammatory MFH exhibits prolonged enhancement on dual-phase enhanced CT scans.

Based on the styling elements of Chinese imperial costume，the characteristics and cultural connotation of blue and white porcelain in the dynasty of Yuan, Ming and Qing and auspicious patterns among the people as well as the traditional paper-cutting art. The paper analyzes the traditional colors and graphic elements by the decomposed and reconstructed of modern graphic designing method, expounds and demonstrates the innovative application of traditional colors and graphic elements in modern home textile design, and then further realizes the Chinese artistic style of home textile design.

The “Calendar Painting” in the period of the Republic of China was a medium of commercial advertising, which was initially a calendar picture for products promotion. The typical images of beautiful women dressed in cheongsams depicted in the calendar paintings became the significant feature of commercial advertising at that time. Cheongsam, as a most important representative of garment for women in the period of the Republic of China, was accompanied by the changes of times of the Republic of China with its production, transformation and development. Based on the studies of calendar advertising paintings during the time of old Shanghai, this paper elaborates such as innovation of cheongsam dress style and pattern design. In the meantime, the characteristics of cheongsam design at that time, the breakthrough on traditional aesthetics for urban women and the effects to contemporary costume design from cheongsam with Shanghai style are also researched in this paper.

Xin-ke Zhang,1,* Tao Qin,1,* Yin-duo Zeng,1,2,* Yuan-yuan Zhao,1 Xue Hou,1 Wen-feng Fang,1 Shao-dong Hong,1 Ting Zhou,1 Zhi-huang Hu,1 Yun-peng Yang,1 Yu-xiang Ma,1 Cong Xue,1 Yan Huang,1 Hong-yun Zhao,1 Li Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: To understand the clinicopathological features of patients with primary pulmonary large-cell neuroendocrine carcinoma (LCNEC), including the frequency of epidermal growth factor receptor (EGFR) mutation, and to explore prognostic factors.Methods: We investigated a cohort of 50 individuals from our center database who were diagnosed with operable pulmonary LCNEC and treated in Sun Yat-sen University Cancer Center. Serum albumin (ALB) and neuron-specific enolase (NSE) were also collected. Survival curves were obtained with the Kaplan–Meier method, and the differences between groups in survival were tested by the log-rank test.Results: The median age was 59 years (range, 40–80 years). Fourteen patients underwent mutational analysis of EGFR; of these, 12 had wild-type EGFR and the remaining two had EGFR mutations in exons. The median disease-free survival (DFS) of pulmonary LCNEC was 49.3 months and that of overall survival (OS) was not reached. DFS and OS were shorter for patients with decreased serum ALB than for patients with normal serum ALB (P=0.003 and P=0.004, respectively). Meanwhile, a high level of NSE was also significantly associated with short DFS and OS (P=0.005 and P=0.000, respectively). Multivariate analysis showed that decrease in serum ALB was an independent prognostic factor for OS (P=0.046).Conclusion: The frequency of EGFR mutation in LCNEC patients is low. Serum ALB and NSE levels are valuable prognostic factors for LCNEC patients. Keywords: pulmonary large cell neuroendocrine carcinoma, ALB, NSE, EGFR, prognosis