RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state

RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss of Rnf43/Znrf3 results in steatohepatitis and in increase in unsaturated lipids, in the absence of dietary fat supplementation. Upon injury, Rnf43/Znrf3 deletion results in defective hepatocyte regeneration and liver cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- and ductal cell-derived organoids we demonstrate that the differentiation defects and lipid alterations are, in part, cell-autonomous. Interestingly, ZNRF3 mutant liver cancer patients present poorer prognosis, altered hepatic lipid metabolism and steatohepatitis/NASH signatures. Our results imply that RNF43/ZNRF3 predispose to liver cancer by controlling the proliferative/differentiation and lipid metabolic state of hepatocytes. Both mechanisms combined facilitate the progression towards malignancy. Our findings might aid on the management of those RNF43/ZNRF3 mutated individuals at risk of developing fatty liver and/or liver cancer

RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state.

RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss of Rnf43/Znrf3 results in steatohepatitis and in increase in unsaturated lipids, in the absence of dietary fat supplementation. Upon injury, Rnf43/Znrf3 deletion results in defective hepatocyte regeneration and liver cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- and ductal cell-derived organoids we demonstrate that the differentiation defects and lipid alterations are, in part, cell-autonomous. Interestingly, ZNRF3 mutant liver cancer patients present poorer prognosis, altered hepatic lipid metabolism and steatohepatitis/NASH signatures. Our results imply that RNF43/ZNRF3 predispose to liver cancer by controlling the proliferative/differentiation and lipid metabolic state of hepatocytes. Both mechanisms combined facilitate the progression towards malignancy. Our findings might aid on the management of those RNF43/ZNRF3 mutated individuals at risk of developing fatty liver and/or liver cancer

Cytotoxicity and ion release of alloy nanoparticles

It is well-known that nanoparticles could cause toxic effects in cells. Alloy nanoparticles with yet unknown health risk may be released from cardiovascular implants made of Nickel–Titanium or Cobalt–Chromium due to abrasion or production failure. We show the bio-response of human primary endothelial and smooth muscle cells exposed to different concentrations of metal and alloy nanoparticles. Nanoparticles having primary particle sizes in the range of 5–250 nm were generated using laser ablation in three different solutions avoiding artificial chemical additives, and giving access to formulations containing nanoparticles only stabilized by biological ligands. Endothelial cells are found to be more sensitive to nanoparticle exposure than smooth muscle cells. Cobalt and Nickel nanoparticles caused the highest cytotoxicity. In contrast, Titanium, Nickel–Iron, and Nickel–Titanium nanoparticles had almost no influence on cells below a nanoparticle concentration of 10 μM. Nanoparticles in cysteine dissolved almost completely, whereas less ions are released when nanoparticles were stabilized in water or citrate solution. Nanoparticles stabilized by cysteine caused less inhibitory effects on cells suggesting cysteine to form metal complexes with bioactive ions in media

Investigation of Nickel-Rare Earth Electrodes for Sodium Borohydride Electrooxidation

Nickel-dysprosium (Ni-Dy) and nickel-samarium (Ni-Sm) alloys were prepared and their morphology, composition and microstructure was analyzed using SEM/EDS and XRD. The alloys were used for fabrication of solid electrodes that were subsequently investigated for borohydride oxidation reaction in alkaline media using cyclic voltammetry, chronoamperometry and chronopotentiometry

Electroanalytical sensing of trace amounts of As(III) in water resources by Gold\u2013Rare Earth alloys

Gold\u2013Rare Earth (Au-RE, RE = Sm, Dy, Ho, Y) alloys were prepared by co-melting stoichiometric amounts of metals. XRPD and SEM/EDX analysis revealed the formation of equiatomic compounds. These alloys were used for the preparation of electrodes for As(III) sensing in aqueous samples. All four electrodes gave a clear response in the presence of As(III) in weakly alkaline media (NaHCO3 + Na2CO3 buffer). Following optimisation of operating parameters (deposition potential of 120.9 V vs SCE and deposition time of 180 s), limits of detection of As(III) at four electrodes were determined to be in 0.8\u20132.3 ppb region. Au-RE electrodes gave a clear response in the presence of Cu(II) as model interferent and, finally, showed the ability for As(III) sensing in a real sample

RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state.

RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss of Rnf43/Znrf3 results in steatohepatitis and in increase in unsaturated lipids, in the absence of dietary fat supplementation. Upon injury, Rnf43/Znrf3 deletion results in defective hepatocyte regeneration and liver cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- and ductal cell-derived organoids we demonstrate that the differentiation defects and lipid alterations are, in part, cell-autonomous. Interestingly, ZNRF3 mutant liver cancer patients present poorer prognosis, altered hepatic lipid metabolism and steatohepatitis/NASH signatures. Our results imply that RNF43/ZNRF3 predispose to liver cancer by controlling the proliferative/differentiation and lipid metabolic state of hepatocytes. Both mechanisms combined facilitate the progression towards malignancy. Our findings might aid on the management of those RNF43/ZNRF3 mutated individuals at risk of developing fatty liver and/or liver cancer

Mn2O3-MO (MO = ZrO2, V2O5, WO3) supported PtNi nanoparticles: Designing stable and efficient electrocatalysts for oxygen reduction and borohydride oxidation

PtNi nanoparticles (NPs) are synthesised by microwave irradiation technique and anchored onto three binary metal oxide (BMO) supports, namely Mn2O3-ZrO2, Mn2O3-V2O5 and Mn2O3-WO3, prepared by solid-state dispersion method. The BMO supports are characterised using SEM, FTIR, N-2-sorption and electrical conductivity measurements. XRD, XPS and TEM analysis confirm the formation of PtNi NPs on the BMO supports. Pt and Ni content over the support materials is set to 10 wt.% for each element. These electrocatalysts activity for oxygen reduction (ORR) and borohydride oxidation (BOR) reaction in alkaline media is assessed for the first time using voltammetric and chronoamperometric techniques. All three PtNi electrocatalysts revealed activity for ORR and BOR, with PtNi/(Mn2O3- ZrO2) exhibiting the highest current densities. The ORR onset potentials were observed to range from 0.84 to 0.97 V vs. RHE, with Tafel slopes ranging from 0.101 to 0.230 V dec(-1). BOR activation energies were found to range from 27 to 30 kJ mol(-1). Obtained results point out PtNi/(Mn2O3- ZrO2) as suitable electrocatalyst for fuel cell applications, particularly for BOR, with lower catalyst price due to partial replacement of the noble metal by a transition metal and improved stability achieved by introducing a binary metal oxide support

Carbon-supported Mo2C electrocatalysts for hydrogen evolution reaction

Molybdenum carbide (Mo2C) nanoparticles supported on two different carbon materials, carbon nanotubes and carbon xerogel, were prepared and characterised using X-ray diffraction, thermogravimetric analysis, scanning and transmission electron microscopy, nitrogen sorption and X-ray photoelectron spectroscopy. The analyses showed similar composition (ca. 27 wt% of Mo2C) and crystallite size (22-28 nm) for the two samples, but significantly different morphologies and specific surface areas. These were subsequently tested as electrocatalysts for hydrogen evolution reaction (HER) in acid media. Using linear scan voltammetry and electrochemical impedance measurements the main reaction parameters were determined, including Tafel slope, charge transfer coefficient and exchange current density. Capacitance properties were examined and correlated with the electrocatalysts activity for HER. The stability of the two materials was also investigated and proved to be very good

Platinum\u2013rare earth electrodes for hydrogen evolution in alkaline water electrolysis

In the new \u201cHydrogen Economy\u201d concept, water electrolysis is considered one of the most promising technologies for hydrogen production. Novel electrocatalytic materials for the hydrogen electrode are being actively investigated to improve the energy efficiency of current electrolysers. Platinum (Pt) alloys are known to possess good catalytic activities towards the hydrogen evolution reaction (HER). However, virtually nothing is known about the effects of rare earth (RE) elements on the electrocatalytic behaviour of Pt towards the HER. In this study, the hydrogen discharge is evaluated in three different Pt\u2013RE intermetallic alloy electrodes, namely Pt\u2013Ce, Pt\u2013Sm and Pt\u2013Ho, all having equiatomic composition. The electrodes are tested in 8 M KOH aqueous electrolytes at temperatures ranging from 25 \ub0C to 85 \ub0C. Measurements of the HER by linear scan voltammetry allow the determination of several kinetic parameters, namely the Tafel coefficients, charge-transfer coefficients, and exchange current densities. Activation energies of 46, 59, 39, and 60 kJ mol 121 are calculated for Pt, Pt\u2013Ce, Pt\u2013Sm and Pt\u2013Ho electrodes, respectively. Results show that the addition of REs improves the activity of the Pt electrocatalyst. Studies are in progress to correlate the microstructure of the studied alloys with their performance towards the HER