Quantitative production of butenes from biomass-derived γ-valerolactone catalysed by hetero-atomic MFI zeolite.

The efficient production of light olefins from renewable biomass is a vital and challenging target to achieve future sustainable chemical processes. Here we report a hetero-atomic MFI-type zeolite (NbAlS-1), over which aqueous solutions of γ-valerolactone (GVL), obtained from biomass-derived carbohydrates, can be quantitatively converted into butenes with a yield of >99% at ambient pressure under continuous flow conditions. NbAlS-1 incorporates simultaneously niobium(V) and aluminium(III) centres into the framework and thus has a desirable distribution of Lewis and Brønsted acid sites with optimal strength. Synchrotron X-ray diffraction and absorption spectroscopy show that there is cooperativity between Nb(V) and the Brønsted acid sites on the confined adsorption of GVL, whereas the catalytic mechanism for the conversion of the confined GVL into butenes is revealed by in situ inelastic neutron scattering, coupled with modelling. This study offers a prospect for the sustainable production of butene as a platform chemical for the manufacture of renewable materials.

Control of zeolite microenvironment for propene synthesis from methanol.

Optimising the balance between propene selectivity, propene/ethene ratio and catalytic stability and unravelling the explicit mechanism on formation of the first carbon-carbon bond are challenging goals of great importance in state-of-the-art methanol-to-olefin (MTO) research. We report a strategy to finely control the nature of active sites within the pores of commercial MFI-zeolites by incorporating tantalum(V) and aluminium(III) centres into the framework. The resultant TaAlS-1 zeolite exhibits simultaneously remarkable propene selectivity (51%), propene/ethene ratio (8.3) and catalytic stability (>50 h) at full methanol conversion. In situ synchrotron X-ray powder diffraction, X-ray absorption spectroscopy and inelastic neutron scattering coupled with DFT calculations reveal that the first carbon-carbon bond is formed between an activated methanol molecule and a trimethyloxonium intermediate. The unprecedented cooperativity between tantalum(V) and Brønsted acid sites creates an optimal microenvironment for efficient conversion of methanol and thus greatly promotes the application of zeolites in the sustainable manufacturing of light olefins.

Combined antitumor effects of 1,25­dihydroxy vitamin D3 and Notch inhibitor in liver cancer.

The combined antitumor effects of 1,25­dihydroxy vitamin D3 [1,25(OH)2D3] and the Notch inhibitor N­[N­-(3,5­difluorophenacetyl)­L­alanyl]­S­phenylglycine t­butyl ester (DAPT, a synthetic γ secretase inhibitor) in liver cancer cells remain to be fully elucidated. In the present study, HepG2 cells were divided into six groups and different treatments were applied: Control, 10­10 M 1,25(OH)2D3, 10­8 M 1,25(OH)2D3, 10­6 M 1,25(OH)2D3, 1 µM DAPT, 5 µM DAPT, 10 µM DAPT, and 10­6 M 1,25(OH)2D3 + 10 µM DAPT. The proliferation, cell cycle, apoptosis, migration and invasion of the cells were then examined. The expression levels of Notch and its ligand Jagged were detected by reverse transcription­quantitative polymerase chain reaction and western blot analyses. The results revealed that 1,25(OH)2D3 inhibited cell proliferation, migration and invasion; arrested cell cycle at the G1 phase, and promoted apoptosis in a concentration­dependent manner between 10­10 and 10­6 M. DAPT inhibited cell proliferation, migration and invasion, arrested cell cycle at the G1 phase, and promoted apoptosis in a concentration­dependent manner between 1 and 10 µM. Additionally, 1,25(OH)2D3 and/or DAPT reduced the expression of Notch1, Notch2, Jagged1 and Jagged2. The co­application of 10 µM DAPT further increased the anticancer effect of 10­6 M 1,25(OH)2D3. Collectively, these results indicated that the treatment of HepG2 cells with 1,25(OH)2D3 inactivated Notch signaling, prevented proliferation, migration and invasion, and promoted apoptosis. The combined application of 1,25(OH)2D3 with DAPT may be a useful treatment for preventing the onset or progression of liver cancer.

Silencing activating transcription factor 2 promotes the anticancer activity of sorafenib in hepatocellular carcinoma cells.

The present study aimed to investigate the anticancer effect of sorafenib combined with silencing of activating transcription factor 2 (ATF2) in hepatocellular carcinoma (HCC) cells and to assess the underlying molecular mechanisms. Huh­7 HCC cell line was selected for the present study. Small interfering RNA (siRNA)­ATF2 sequence was constructed to silence ATF2 expression. The experiment was divided into 6 groups: i) Control; ii) vector; iii) sorafenib (6.8 µM); iv) vector+sorafenib; v) siRNA­ATF2; and vi) siRNA­ATF2+sorafenib groups. Cell proliferation, apoptosis, migration and invasion were detected following treatments with sorafenib and/or ATF2 silencing. Additionally, expression of tumor necrosis factor (TNF)­α and c­Jun N­terminal kinase 3 (JNK3) was detected using reverse transcription­quantitative polymerase chain reaction and western blotting. The current findings revealed that siRNA­ATF2 significantly reduced ATF2 expression. Cell proliferation, migration and invasion abilities in the sorafenib and siRNA­ATF2 groups were significantly reduced compared with the control group (P<0.05). Apoptotic rate in the sorafenib and siRNA­ATF2 groups was significantly increased compared with the control group (P<0.05). The mRNA and protein expression levels of ATF2 in the sorafenib or siRNA­ATF2 groups was significantly reduced when compared with control group. The phosphorylation of ATF2 was also reduced following sorafenib treatment or ATF2 silence. Although JNK3 mRNA expression level was not affected, the phosphorylation level of JNK3 was significantly promoted following sorafenib treatment or ATF2 silencing. Additionally, TNF­α mRNA and protein expression levels were increased following sorafenib treatment or ATF2 silencing. It is of note that siRNA­ATF2 treatment promoted the anticancer activity of sorafenib in Huh­7 cells. Additionally, siRNA­ATF2+sorafenib treatment combined additionally promoted TNF­α expression and phosphorylation of JNK3. Combined siRNA­ATF2 and sorafenib treatment had a greater anticancer effect compared with sorafenib or ATF2 silencing alone. The possible mechanism involved in the anticancer effect of sorafenib and ATF2 silencing may be associated with the activation of the TNF­α/JNK3 signaling pathway.

Facile synthesis of a high-performance titanosilicate catalyst with controllable defective Ti(OSi)3OH sites.

A novel TS-1 (TS-1S) catalyst with newly-generated defects, i.e. Ti(OSi)3OH species, which exhibits the highest reactivity among different Ti species, is constructed in an ingenious strategy. This also provides a promising way to effectively tune the intrinsic nature of Ti active centres in other titanosilicates.

CXC195 induces apoptosis and endoplastic reticulum stress in human hepatocellular carcinoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

CXC195 exhibits strong protective effects against neuronal apoptosis by exerting antioxidant activity. However, the pharmacological function of CXC195 in cancer remains to be elucidated. The present study demonstrated that CXC195 exhibited significant cytotoxic effects, and induced cell cycle arrest and apoptosis in HepG2 human hepatocellular carcinoma (HCC) cell lines. Following treatment of HepG2 cells with 150 µΜ CXC195 for 24 , cell viability and the apoptotic rate were assessed using an MTT assay and Annexin V/propidium iodide staining followed by flow cytometric analysis. Molecular markers of the cell cycle, apoptosis, mitochondrial function and endoplasmic reticulum (ER) stress were analyzed by western blot or polymerase chain reaction analysis. Caspase activation, cytochrome c and apoptosis­inducing factor release, and analysis of the B cell lymphoma 2 (Bcl­2)­associated X protein/Bcl­2 ratio demonstrated that the anticancer effects of CXC195 in HepG2 cells were mediated by caspase and mitochondria­dependent apoptosis. CXC195 also induced the expression of ER stress­associated proteins, including CCAAT­enhancer­binding protein homologous protein, and glucose­regulated proteins 94 and 78, and led to the activation of multiple branches of ER stress transducers, including inositol­requiring enzyme 1α­apoptosis signal­regulating kinase­p38/c­Jun N­terminal kinase, and protein kinase R­like endoplasmic reticulum kinase­eukaryotic translation initiation factor 2α­activating transcription factor (ATF)4 and ATF6, in the HepG2 cells. In addition, CXC195 inhibited the phosphorylation of phosphoinositide 3­kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) in the HepG2 cells. These effects were enhanced following treatment with selected inhibitors of PI3K (LY294002), Akt (SH­6) and mTOR (rapamycin). Furthermore, these inhibitors enhanced the pro­apoptotic effects of CXC195 in the HepG2 cells. In conclusion, the results of the present study indicated that CXC195 induced apoptosis and ER stress in HepG2 cells through the inhibition of the PI3K/Akt/mTOR signaling pathway.