Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.

Polymer Hydrogel Supported Ni/Pd Alloys for Hydrogen Gas Production from Hydrolysis of Dimethylamine Borane with a Long Recyclable Lifetime.

Hydrogen gas production can be produced from dimethylamine borane by the catalytic effect of metal nanoparticles. Past research efforts were heavily focused on dehydrogenation in organic solvents. In this study, hydrolysis of the borane in aqueous solutions was investigated, which bears two significant advantages: that two-thirds of the hydrogen generated originate from water and that the hydrogen storage materials are non-flammable. Polymer hydrogels serve as good carriers for metal particles as catalysts in aqueous solutions. Kinetic analysis of hydrogen production was performed for Ni/Pd bimetallic nanoclusters dispersed in a polymer hydrogel with a 3-D network structure. The reaction catalyzed by the bimetallic nanoclusters has an activation energy of only 34.95 kJ/mol, considerably lower than that by Ni or other metal catalysts reported. A significant synergistic effect was observed in the Ni/Pd bimetallic catalysts (Ni-Pd = 20/1) with a higher activity than Pd or Ni alone. This proves the alloy nature of the nanoparticles in the borane hydrolysis and the activation of water and borane by both metals to break the O-H and B-H bonds. The hydrogel with the Ni/Pd metal can be recycled with a much longer lifetime than all the previously prepared catalysts. The aqueous borane solutions with a polymer hydrogel can become a more sustainable hydrogen supplier for long-term use.

In situ fabrication of Ag3PO4/TiO2 nanotube heterojunctions with enhanced visible-light photocatalytic activity.

Ag3PO4/TiO2 nanotube (TNT) heterojunctions were fabricated via a facile in situ growth method. Hemispherical Ag3PO4 nanocrystals were uniformly grown on the TNT surface, and their size was confined to 5-10 nm. A joint area was distinctly observed between the Ag3PO4 nanocrystals and TNT, indicating the formation of a Ag3PO4/TNT heterojunction. Compared with pure Ag3PO4, the Ag3PO4/TNT heterojunction possesses more active sites, less bulk defects, more efficient electron-hole separation, as well as better dye adsorption properties, and thus exhibits a significantly elevated photocatalytic activity for Rhodamine B (RhB) degradation. The study of the reactive species demonstrates that the photocatalytic degradation of RhB over the Ag3PO4/TNT heterojunction is primarily driven by both photogenerated h(+) and ˙OH radicals. This easily-fabricated Ag3PO4/TNT heterojunction with promising photocatalytic activity may find potential applications in energy and environmental related areas.

Fluorous metal-organic frameworks with enhanced stability and high H2/CO2 storage capacities.

A new class of metal-organic frameworks (MOFs) has been synthesized by ligand-functionalization strategy. Systematic studies of their adsorption properties were performed at low and high pressure. Importantly, when fluorine was introduced into the framework via the functionalization, both the framework stabilities and adsorption capacities towards H2/CO2 were enhanced significantly. This consequence can be well interpreted by theoretical studies of these MOFs structures. In addition, one of these MOFs TKL-107 was used to fabricate mixed matrix membranes, which exhibit great potential for the application of CO2 separation.

Biosilica-coated kappa-carrageenan microspheres for yeast alcohol dehydrogenase encapsulation.

In this study, a novel polysaccharide/inorganic hybrid biocomposite was prepared through biomineralization-inspired process for efficient immobilization of yeast alcohol dehydrogenase (YADH). YADH-encapsulated kappa-carrageenan microspheres (KCM) were first coated with chitosan, which was used to guide and catalyze the biomimetic formation of silica, and then coated with silica derived from tetraethoxysiliane (TEOS). Scanning electron microscopy (SEM) equipped with a energy dispersive X-ray spectrometer (EDX) was employed to investigate the composition and thickness of silica film. Compared with KCM, the silica-coated kappa-carrageenan microspheres (SKCM) containing YADH exhibited improved anti-swelling and catalytic properties. Enzyme leakage of YADH in KCM was detected to be 63.9% after 1 h, while the enzyme leakage in SKCM was as low as 18.2%. The KCM adsorbed water promptly and after 1 h maximum water uptake can be as high as 1576 wt%, while the water uptake of SKCM was only 143 wt% even after 48 h. The optimum pH and temperature for encapsulated YADH were pH 6.5 and 25 degrees C, which were just the same as those for free YADH, but the encapsulated YADH exhibited broader pH and temperature ranges for high activity. Furthermore, the relative activity of YADH in KCM declined almost to zero after 8 recycles, while the relative activity of YADH in SKCM still maintained more than 50%. The significantly increased recycling stability of YADH in SKCM may be attributed to the effective inhibition of enzyme leakage by the compact biosilica layer.

Preparation of novel silica-coated alginate gel beads for efficient encapsulation of yeast alcohol dehydrogenase.

Biomimetic formation has undoubtedly inspired the preparation of novel organic-inorganic hybrid composites. In this study, silica-coated alginate gel beads were prepared by coating the surface of alginate gel beads with silica film derived from tetramethoxysilane (TMOS). The composition and structure of the silica film were characterized by FT-IR and SEM equipped with EDX. The swelling behavior of silica-coated alginate gel beads was studied to be more stable against swelling than that of alginate gel beads. The results showed that silica-coated alginate gel beads exhibited appropriate diffusion property. The effective diffusion coefficient (D(e)) of NADH in silica-coated alginate beads was 1.76 x 10(-10) m2/s, while the effective diffusion coefficient in alginate beads was 1.84 x 10(-10) m2/s. The model enzyme yeast alcohol dehydrogenase (YADH) was encapsulated in silica-coated alginate and pure alginate beads, respectively. Enzyme leakage of YADH in alginate gel beads was determined to be 32%, while the enzyme leakage in silica-coated alginate gel beads was as low as 11%. Furthermore, the relative activity of YADH in alginate gel beads decreased almost to zero after 10 recycles, while the relative activity of YADH in silica-coated alginate gel beads was 81.3%. The recycling stability of YADH in silica-coated alginate gel beads was found to be increased significantly mainly due to the effective inhibition of enzyme leakage by compact silica film.

Improved protein-adsorption-resistant property of PES/SPC blend membrane by adjustment of coagulation bath composition.

To improve surface protein-adsorption-resistant property of polyethersulfone (PES) membranes, soybean phosphatidylcholine (SPC) was added to PES casting solution. The blend membranes were prepared by a phase inversion method in a wet process. The surface of PES/SPC blend membranes was characterized by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS data revealed that the phosphorylcholine (PC) groups were concentrated at the surface by changing the composition of coagulation bath. Addition of N,N-dimethylformamide (DMF) in coagulation bath could prolong coagulation time and facilitate the migration of SPC from polymer bulk to membrane surface. The PES/SPC blend membranes dramatically reduced BSA and fibrinogen adsorption compared to PES control membrane due to effective immobilization of PC groups at the surface of PES/SPC blend membranes.

Remarkable reduction of irreversible fouling and improvement of the permeation properties of poly(ether sulfone) ultrafiltration membranes by blending with pluronic F127.

Hydrophilic modification of ultrafiltration membranes was achieved through blending of Pluronic F127 with poly(ether sulfone) (PES). The chemical composition and morphology changes of the membrane surface were confirmed by water contact angle, X-ray photoelectron spectroscopy, scanning electron microscopy, and protein adsorption measurements. The decreased static water contact angle with an increase in the Pluronic F127 content indicated an increase of surface hydrophilicity. XPS analysis revealed enrichment of PEO segments of Pluronic F127 at the membrane surface. The apparent protein adsorption amount decreased significantly from 56.2 to 0 microg/cm(2) when the Pluronic F127 content varied from 0% to 10.5%, which indicated that the blend membrane had an excellent ability to resist protein adsorption. The ultrafiltration experiments revealed that the Pluronic F127 content had little influence on the protein rejection ratio and pure water flux. Most importantly, at a high Pluronic F127 content membrane fouling, especially irreversible fouling, has been remarkably reduced. The flux recoveries of blend membranes reached as high as 90% after periodic cleaning in three cycles.

[Membrane used for separation of the effective parts and components of traditional Chinese medicine].

Membrane separation, as an efficient and green technology, has found more and more research and development reports in the separation and purification of the effective parts and components of traditional Chinese medicine. The basic principle and mechanism was first described in this paper, and the applicability and technological advantage was analyzed accordingly. Then, the separation performance of commonly employed membrane materials including polymeric materials such as polysulfones, cellulose acetate, polyacrylonitrile as well as inorganic materials was compared out and the application examples were presented. Finally, the major considerations in choosing the membrane materials were tentatively listed, including the physical and chemical stability, the flux and selectivity, membrane fouling, and pretreatment of membrane surface.