Cell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis, a type of programmed necrosis, has a role in cisplatin-induced AKI. We found that inhibition of any of the core components of the necroptotic pathway-receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)-by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination of cytokines (TNF-a, TNF-related weak inducer of apoptosis, and IFN-g) that were upregulated in proximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatintreated mice was partially diminished in RIP3-or MLKL-deficient mice, suggesting a positive feedback loop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI.

Photocatalytic ammonia synthesis is exciting but quite challenging with a very moderate yield at present. One of the greatest challenges is to develop highly active centers in a photocatalyst for N2 reduction under ambient conditions. Herein, porous carbon‐doped anatase TiOx (C‐TiOx) nanosheets with high‐concentration active sites of Ti3+ are presented, which are produced by layered Ti3SiC2 through a reproducible bottom‐up approach. It is shown that the high‐concentration Ti3+ sites are the major species for the significant increase in N2 photoreduction activity by the C‐TiOx. Such bottom‐up substitutional doping of C into TiO2 is responsible for both visible absorption and generation of Ti3+ concentration. Together with the porous nanosheets morphology and the loading of a Ru/RuO2 nanosized cocatalyst for enhanced charge separation and transfer, the optimal C‐TiOx with a Ti3+/Ti4+ ratio of 72.1% shows a high NH3 production rate of 109.3 µmol g−1 h−1 under visible‐light irradiation and a remarkable apparent quantum efficiency of 1.1% at 400 nm, which is the highest compared to all TiO2‐based photocatalysts at present.

Recent studies have revealed that human sodium taurocholate cotransporting polypeptide (SLC10A1 or NTCP) is a functional cellular receptor for hepatitis B virus (HBV). However, whether human NTCP can support HBV infection in mouse hepatocyte cell lines has not been clarified. Because an HBV-permissible mouse model would be helpful for the study of HBV pathogenesis, it is necessary to investigate whether human NTCP supports the susceptibility of mouse hepatocyte cell lines to HBV. The results show that exogenous human NTCP expression can render non-susceptible HepG2 (human), Huh7 (human), Hepa1-6 (mouse), AML-12 (mouse) cell lines and primary mouse hepatocyte (PMH) cells susceptible to hepatitis D virus (HDV) which employs HBV envelope proteins. However, human NTCP could only introduce HBV susceptibility in human-derived HepG2 and Huh7 cells, but not in mouse-derived Hepa1-6, AML-12 or PMH cells. These data suggest that although human NTCP is a functional receptor that mediates HBV infection in human cells, it cannot support HBV infection in mouse hepatocytes. Our study indicated that the restriction of HBV in mouse hepatocytes likely occurs after viral entry but prior to viral transcription. We have excluded the role of mouse hepatocyte nuclear factors in the restriction of the HBV life cycle and showed that knockdown or inhibition of Sting, TBK1, IRF3 or IRF7, the components of the anti-viral signaling pathways, had no effect on HBV infection in mouse hepatocytes. Therefore, murine restriction factors that limit HBV infection need to be identified before a HBV-permissible mouse line can be created. INTRODUCTIONHepatitis B virus (HBV) is an enveloped virus containing a 3.2-kb genome of partially double-stranded DNA encoding four overlapping reading frames. The HBV envelope consists of the small (S), middle (M) and large (L) envelope proteins. These multiple transmembrane proteins share the same Cterminal domain corresponding to the S protein, but differ at their N-terminal domains. 1 HBV infection constitutes a serious threat to public health worldwide because more than 350 million people are chronically infected with HBV. Chronic HBV infection causes serious consequences, including chronic hepatitis, cirrhosis and hepatocellular carcinoma, and is responsible for more than one million deaths each year. 2 Hepatitis D virus (HDV) is a small satellite RNA virus of HBV. It carries all the three HBV envelope proteins and

Microbial-Induced Calcium Carbonate Precipitation (MICP) is an innovative ground improvement technique which can enhance the strength and stiffness of soils and can also control their hydraulic conductivity. These engineering properties of MICP-treated soils are affected by the particle-scale behaviour of the precipitated calcium carbonate, i.e. composition, amount and distribution, which are controlled by the MICP process occurring at the particlescale. In this study, we designed and fabricated a microfluidic chip to improve our understanding of MICP at particle-scale by observing the behaviour of bacteria and calcium carbonate crystals during this process. We found that bacteria became evenly distributed throughout the microfluidic chip after the injection of bacterial suspension, grew during bacterial settling, and detached during the injection of cementation solution. Bacteria aggregated during the cementation solution injection, and calcium carbonate crystals formed at narrow pore throats or open pore bodies either during or after cementation solution injections.