The molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system.Here we interrogate the potential of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We show that organoids derived from HBV-infected patients display an aberrant early cancer gene signature, which clusters with the HCC cohort on the TCGA LIHC dataset and away from healthy liver tissue. Furthermore, we demonstrate HBV infection in healthy donor liver organoids after challenge with recombinant virus or HBV infected patient serum. Ex vivo infected liver organoids produced cccDNA, expressed intracellular HBV RNA and proteins, and produced infectious HBV. HBV replication supported by ex vivo infected liver organoids was blocked by treatment with Tenofovir, highlighting the potential of this model system as a primary differentiated hepatocyte platform for HBV drug screening. Interestingly, transgenic organoids exogenously over expressing the HBV receptor NTCP by lentiviral transduction are not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. Finally, we generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription.

Nickel is widely used as a catalyst in chemical and petrochemical industries. Due to their low cost competing replacements, these are the catalysts of choice in several industries. Such catalysts use silica and alumina as supports [1]. As these catalysts, is used, metals from the feedstock deposit on the internal surface of its pores and its external surface, eventually plugging the pores and decreasing the activity of the catalyst to such an extent it does not give the desired product quality [2]. If the regeneration of these catalysts is not economically feasible, they are discarded from petroleum processing and, at present, large dumps of spent catalysts are growing. Hence, the spent catalysts disposal poses an unavoidable environmental issue, which necessarily requires high capital investment, huge swaths of land and massive efforts [3]. In many countries, the hazardous nature of the spent catalysts is attracting the attention of environmental authorities and the refiners are suffering pressures from them for safe handling of spent catalysts. Several alternative methods such as reclamation of metals, disposal in landfills, utilisation as raw materials to produce other useful products and regeneration and reuse are available to the refiners to deal with the spent catalyst problem. The choice between these options depends on technical feasibility and economic considerations [4]. The recovery methods of nickel from spent catalysts can be classified as thermal treatment, chlorination, acid leaching, alkali leaching, bioleaching. The pyrometallurgy process was applied to the spent catalyst by Llanos et al. [5] who used alkali roasting, and Kim et al.[6] explored a low-temperature sulphuric acid baking and mild acid leaching for maximum dissolution of metal values from a spent Ni-MO/Al 2 O 3 hydroprocessing catalyst. However, hydrometallurgical process can be regarded as the desired route for recovery of metals due to its economic operation, environmentally friendly and simplicity. Alkaline or acidic leaching was used by many researchers by using many reagents. Marcantonio [7] invented a process to extract valuable metals. In this study, the spent catalyst was roasted at (400-600°C) and then contacted with an aqueous solution of ammonium sulfate ((NH 4 ) 2 SO 4 ), ammonium carbonate ((NH 4 ) 2 CO 3 ) and hydrogen peroxide. The optimum leach conditions were 0.5 M (NH 4 ) 2 SO 4 , 1 M (NH 4 ) 2 CO 3 and 80°C for three hours was obtained. Angelidis et al. applied a two-step of leaching alkali (sodium hydroxide) followed by acid (sulfuric acid) procedure and studied the selective recovery of metals, such as Mo, Co and Ni, from hydrodesulfurization (MoNi/Al 2 O 3 -SiO 2 and Mo-Co/Al 2 O 3 ) catalysts [8]. Al-Mansi and Abdel Monem used sulfuric acid as a solvent to recovery of nickel from the spent catalyst (NiO/Al 2 O 3 ) resulting from the steam reforming process [9]. It was found that 99% of nickel was extracted at 50% sulfuric acid concentration, particle size less than 500 µm, solid to liquid ratio (1:12) by weight...