Association of CX3CL1 and CX3CR1 Expression with Liver Fibrosis in a Mouse Model of Schistosomiasis

Immunopathological mechanisms of schistosomiasis,a debilitating parasitic disease,are still unclear.In this study,we investigated the involvement of CX3C chemokine ligand 1(CX3CL1)and its sole receptor CX3CR1 in the development of liver fibrosis in schistosomiasis.The animal model of schistosomiasis was established by infection of C57BL/6 mice with Schistosoma japonicum cercariae;mice injected with carbon tetrachloride(CCl4)were used as positive control of liver injury.After 4 and 8 weeks,the degree of liver lesions was assessed by hematoxylin and eosin staining,serum levels of hyaluronic acid(HA)were analyzed by a chemiluminescence immunoassay,liver fibrosis was evaluated by immunohistochemistry analysis ofα-smooth muscle actin(α-SMA)expression,and CX3CL1 and CX3CR1 expression in the liver was measured by immunohistochemistry and real-time PCR.The results showed that at 8 weeks after Schistosoma infection,serum HA levels were increased andα-SMA-expressing cells appeared in the liver,indicating fibrogenesis.CX3CL1-and CX3CR1-positive cells were observed in the outer layer of granulomas formed around Schistosoma eggs in liver tissues,which was consistent with the significant upregulation of hepatic CX3CL1 and CX3CR1 mRNA expression at 4 and 8 weeks post-infection.Furthermore,correlation analysis revealed positive association between CX3CL1 and CX3CR1 expression and serum HA levels at 8 weeks post-infection,indicating a link between fibrogenesis and the CX3CL1/CX3CR1 axis in schistosomiasis.In conclusion,our data suggest the involvement of CX3CL1 and CX3CR1 in the progression of liver fibrosis caused by Schistosoma infection.

Molecular Cloning,Characterization and Expression Analysis of Woodchuck Retinoic Acid-Inducible GeneⅠ

Cytosolic retinoic acid-inducible gene I（RIG-I） is an important innate immune RNA sensor and can induce antiviral cytokines, e.g., interferon-β（IFN-β）. Innate immune response to hepatitis B virus（HBV） plays a pivotal role in viral clearance and persistence. However, knowledge of the role that RIG-I plays in HBV infection is limited. The woodchuck is a valuable model for studying HBV infection. To characterize the molecular basis of woodchuck RIG-I（w RIG-I）, we analyzed the complete coding sequences（CDSs） of w RIG-I, containing 2778 base pairs that encode 925 amino acids. The deduced w RIG-I protein was 106.847 k D with a theoretical isoelectric point（p I） of 6.07, and contained three important functional structures [caspase activation and recruitment domains（CARDs）, DEx D/H-box helicases, and a repressor domain（RD）]. In woodchuck fibroblastoma cell line（WH12/6）, w RIG-I-targeted small interfering RNA（si RNA） down-regulated RIG-I and its downstrean effector–IFN-β transcripts under RIG-I＇ ligand, 5＇-ppp double stranded RNA（ds RNA） stimulation. We also measured m RNA levels of w RIG-I in different tissues from healthy woodchucks and in the livers from woodchuck hepatitis virus（WHV）-infected woodchucks. The basal expression levels of w RIG-I were abundant in the kidney and liver. Importantly, w RIG-I was significantly up-regulated in acutely infected woodchuck livers, suggesting that RIG-I might be involved in WHV infection. These results may characterize RIG-I in the woodchuck model, providing a strong basis for further study on RIG-I-mediated innate immunity in HBV infection.

Simultaneous switching of supramolecular chirality and organizational chirality driven by Coulomb expansion

Chiral switching is a fascinating topic and plays an important role in construction of homochirality.Nevertheless,due to the complexity and flexibility of noncovalent interactions,switching the chirality of entire supramolecular assemblies has hitherto remained a challenge.Here we report the electric field-controlled chirality switching of pentacene pinwheel arrays and two-dimensional(2D)network domains.Pentacene molecules on Cd(0001)surface form the porous network structure with building blocks of hexamer pinwheels.Driven by the electric field from a scanning tunneling microscopy(STM)tip,the supramolecular chirality of pentacene pinwheels and the organizational chirality of entire network domains can be simultaneously switched from one enantiomorph to another.Furthermore,such chiral switching is reversible and repeatable under successive voltage pulses.First-principles calculations demonstrate that electric field significantly modulates the interfacial charge transfer and induces the Coulomb expansion of pentacene layers,and the subsequent reaggregation leads to the chiral flipping of the supramolecular pinwheels and 2D domains.Our results provide a new strategy for dynamic control of the 2D chiral structures and help to steer the supramolecular assembly toward homochirality.