There remain significant obstacles in developing biologics to treat primary biliary cholangitis (PBC). Although a number of agents have been studied both in murine models and human patients, the results have been relatively disappointing. IL-22 is a member of the IL-10 family and has multiple theoretical reasons for predicting successful usage in PBC. We have taken advantage of an IL-22 expressing adeno-associated virus (AAV-IL-22) to address the potential role of IL-22 in not only protecting mice from autoimmune cholangitis, but also in treating animals with established portal inflammation. Using our established mouse model of 2-OA-OVA immunization, including α-galactosylceramide (α-GalCer) stimulation, we treated mice both before and after the onset of clinical disease with AAV-IL-22. Firstly, AAV-IL-22 treatment given prior to 2-OA-OVA and α-GalCer exposure, i.e. before the onset of disease, significantly reduces the portal inflammatory response, production of Th1 cytokines and appearance of liver fibrosis. It also reduced the liver lymphotropic chemokines CCL5, CCL19, CXCL9, and CXCL10. Secondly, and more importantly, therapeutic use of AAV-IL-22, administered after the onset of disease, achieved a greater hurdle and significantly improved portal pathology. Further the improvements in inflammation were negatively correlated with levels of CCL5 and CXCL10 and positively correlated with levels of IL-22. In conclusion, we submit that the clinical use of IL-22 has a potential role in modulating the inflammatory portal process in patients with PBC.

An integrated strategy of molecular design and conjugated polymer doping is proposed to improve the electronic characteristics for organic field effect transistor (OFET) applications. Here, a series of soluble naphthalene diimide (NDI)-based random donor−acceptor copolymers with selenophene π-conjugated linkers and four acceptors with different electron-withdrawing strengths (named as rNDI-N/S/NN/SS) are synthesized, characterized, and used for OFETs. N-type doping of 5,6,12,12a,13,18,18a,19-octahydro-5,6-dimethyl-13,18[1′,2′]]benzodiazocine potassium triflate adduct (DMBI-BDZC) is successfully demonstrated. The undoped rNDI-N, rNDI-NN, and rNDI-SS samples exhibit ambipolar charge transport, while rNDI-S presents only a unipolar n-type characteristic. Doping with DMBI-BDZC significantly modulates the performance of rNDI-N/S OFETs, with a 3-to 6-fold increase in electron mobility (μ e ) for 1 wt % doped device due to simultaneous trap mitigation, lower contact resistance (R C ), and activation energy (E A ), and enhanced crystallinity and edge-on orientation for charge transport. However, the doping of intrinsic pro-quinoidal rNDI-NN/SS films exhibits unchanged or even reduced device performance. These findings allow us to manipulate the energy levels by developing conjugated copolymers based on various acceptors and quinoids and to optimize the dopant−polymer semiconductor interactions and their impacts on the film morphology and molecular orientation for enhanced charge transport.

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