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Activation of pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, is known to induce liver enlargement, but the molecular signals and the cell types responding to PXR-induced hepatomegaly remain unknown. In this study, the effect of PXR activation on liver enlargement and cell change was evaluated in several strains of genetically-modified mice and animal models. Lineage labelling using AAV-Tbg-Cre-treated Rosa26 mice or Sox9-Cre , Rosa26 mice was performed and Pxr-null mice or AAV Yap shRNA-treated mice were used to confirm the role of PXR or YAP. Treatment with selective PXR activators induced liver enlargement and accelerated regeneration in wild-type and PXR-humanized mice but not in Pxr-null mice by increase of cell size, induction of a regenerative hybrid hepatocyte (HybHP) reprogramming, and promotion of hepatocyte and HybHP proliferation. Mechanistically, PXR interacted with yes-associated protein (YAP) and PXR activation induced nuclear translocation of YAP. Blockade of YAP abolished PXR-induced liver enlargement in mice. These findings revealed a novel function of PXR in enlarging liver size and changing liver cell fate via activation of the YAP signalling pathway. These results have implications for understanding the physiological functions of PXR and suggest the potential for manipulation of liver size and liver cell fate. This article is protected by copyright. All rights reserved.

demonstrating a great potential in nextgeneration photovoltaic technology, lightemitting devices, and photodetectors. [1][2][3][4] Especially, their flourishing application in all-inorganic perovskite solar cell (PSC) with the recorded power conversion efficiency (PCE) over 11% provides a chance to balance the incompatible efficiency and stability of the organicinorganic hybrid PSCs. [5][6][7][8][9][10] Comparing to state-of-the-art PSC, the ultrahigh voltage output and commercializationavailable stability of CsPbBr 3 PSCs are the unique advantages for self-driving high-voltage-required electronic components. However, there is always a reversible phase transition between 3D CsPbBr 3 , 2D CsPb 2 Br 5 , and 0D Cs 4 PbBr 6 under external stimuli such as, hightemperature annealing treatment and solvent deprivation, [11,12] resulting in the inevitable co-formation of the congruent phases in the final product, which disorders the efficiency enhancement mechanism, as well as, the photoluminescence (PL) origin between CsPbBr 3 and Cs 4 PbBr 6 . [13] As well known, the electronic properties of these Cs-Pb-Br derivatives are changeable because the dimensionality of corner-sharing [PbBr 6 ] 4− octahedra strongly determines the exciton dissociation and recombination processes. The disconnected [PbBr 6 ] 4− units from 3D to 2D and then 0D phase will gradually minimize the adjacent electronic overlap, leading to a localized state and increased quantum confinement effect for detrimental charge recombination. [14,15] Therefore, the precise control on the phase composition in CsPbBr 3 film is important to enhance the optoelectronic performance.Because of the lower solubility of CsBr than PbBr 2 in N,N-dimethyl formamide (DMF) and/or dimethylsulfoxide solvent, high-quality CsPbBr 3 films for solar cells are generally fabricated by two-step or multi-step method, which involves first spin-coated PbBr 2 and subsequent reaction with CsBr. [16][17][18] Although vapor growth method and modified multistep spin-coating strategy have been proposed, [6,19] there is still a great challenge to accurately control the stoichiometric ratio and to hinder the formation of low-dimensional impurity phases. Especially, for traditional multi-step solution-processable technology, aiming to obtain idea perovskite film, there isThe precise phase control of Cs-Pb-Br derivatives from 3D CsPbBr 3 to 0D Cs 4 PbBr 6 highly determines the photovoltaic performance of all-inorganic CsPbBr 3 perovskite solar cells (PSCs). Herein, the preferred phase conversion from precursor to Cs-Pb-Br derivatives is revealed by theoretically calculating the Gibbs free energies (∆G) of various phase conversion processes, allowing for a simplified multi-step solution-processable spin-coating method to hinder the formation of detrimental 0D Cs 4 PbBr 6 phase and enhance the photovoltaic performance of a PSC because of its large exciton binding energy, which is regarded as a recombination center. By further accelerating the interfacial charge extraction with a novel 2D transition m...

Lipidomics, which reveals comprehensive characterization of molecular lipids, is a rapidly growing technology used in biomedical research. Lipid extraction is a critical step in lipidomic analysis. However, the effectiveness of different lipid extract solvent systems from cellular samples still remains unclear. In the current study, the protocol of reverse-phase liquid chromatography mass spectrometry (LC/MS)-based lipidomics was optimized for extraction and detection of lipids from human pancreatic cancer cell line PANC-1. Four different extraction methods were compared, including methanol/methyl-tert-butyl ether (MTBE)/HO, methanol/chloroform, methanol/MTBE/chloroform, and hexane/isopropanol. Data were acquired using high-resolution mass spectrometry in positive and negative ion modes respectively. The number of total detected and identified lipids was assessed with the aid of automated lipid identification software LipidSearch. Results demonstrated that methanol/MTBE/HO provided a better extraction efficiency for different lipid classes, which was chosen as the optimized extraction solvent system. This validated method enables highly sensitive and reproducible analysis for a variety of cellular lipids, which was further applied to an untargeted lipidomic study on human pancreatic cancer PANC-1 cell lines. Moreover, this optimized extraction solvent system can be further applied to other cancer cell lines with similar chemical and physical properties. Graphical abstract Optimized UHPLC-ESI-HRMS-based lipidomic analysis of cancer cells.

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Background and Aims: Peroxisome proliferator-activated receptor α (PPARα, NR1C1) is a ligand-activated nuclear receptor involved in the regulation of lipid catabolism and energy homeostasis. PPARα activation induces hepatomegaly and plays an important role in liver regeneration, but the underlying mechanisms remain unclear. Approach and Results: In this study, the effect of PPARα activation on liver enlargement and regeneration was investigated in several strains of genetically modified mice. PPARα activation by the specific agonist WY-14643 significantly induced hepatomegaly and accelerated liver regeneration after 70% partial hepatectomy (PHx) in wild-type mice and Ppara fl/fl mice, while these effects were abolished in hepatocyte-specific Ppara-deficient (Ppara ΔHep ) mice. Moreover, PPARα activation promoted hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. Mechanistically, PPARα activation regulated expression of yes-associated protein (YAP) and its downstream targets (connective tissue growth factor, cysteine-rich angiogenic inducer 61, and ankyrin repeat domain 1) as well as proliferation-related proteins (cyclins A1, D1, and E1). Binding of YAP with the PPARα E domain was critical for the interaction between YAP and PPARα. PPARα activation further induced nuclear translocation of YAP. Disruption of the YAP-transcriptional enhancer factor domain family member (TEAD) association significantly suppressed PPARα-induced hepatomegaly and hepatocyte enlargement and proliferation. In addition, PPARα failed to induce

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