The fitting curve established by delta response units with different standard PCV2 Cap concentrations ranged from 0.5 µg/mL to 10 µg/mL.

<p>The fitting curve established by delta response units with different standard PCV2 Cap concentrations ranged from 0.5 µg/mL to 10 µg/mL.</p

The biomembrane structure for the preparation of the biosensing membrane for the detection of the PCV2.

<p>(1) Au-S bond was formed after the association occurred between the thiol of mercapto propionic acid with the Au atom, where the 1 mol/L mercaptopropionic acid was used. (2) PCV2 antibodies were immobilized on the gold film surface by binding the peptide bond.</p

Contrast resolution obtained from both SPR immunoassay and PCV2 detection kits.

<p>Contrast resolution obtained from both SPR immunoassay and PCV2 detection kits.</p

FGFR4 is required for FGF19-mediated liver tumorigenesis.

<p><i>A</i>, Multiple, large, raised tumors (arrows) protruding from the hepatic surface of a 10-month-old FGF19-TG:FGFR4-WT mouse (left panel). Liver from a 10-month-old FGF19-TG:FGFR4-KO mouse (right panel). <i>B</i>, BrdU incorporation in female (left panel) and male (right panel) FGF19-TG or wild type mice bred with FGFR4-KO or FGFR4-WT mice. <i>C</i>, Prevalence of liver tumors in male and female FGF19-TG mice treated with DEN as determined by gross and histological examinations. <i>D</i>, Multiple, large, raised tumors (arrows) on the surface of the liver of a 4-month-old FGF19-TG:FGFR4-WT mouse treated with DEN. <i>E</i>, Liver weights from FGF19-TG or wild type female (left panel) and male (right panel) mice treated with DEN. The asterisk (*) indicates that the weight of the liver could not be measured from the 7-month time point for male FGF19-TG mice treated with DEN because none survived past 6 months of age. <i>F</i>, Liver weights of FGF19-TG or wild type female (left panel) and male (right panel) FGFR4-KO mice treated with DEN.</p

In vivo efficacy of LD1.

<p><i>A</i>, LD1 inhibits FGF19-regulated <i>FOS</i> expression in mouse liver. The results are represented as fold expression relative to <i>FOS</i> levels in the livers of non-treated mice. <i>B</i>, LD1 (30 mg/kg; once weekly) inhibits HUH7 xenograft tumor growth in vivo. <i>C</i>, Effects of LD1 on the mRNA expression of <i>FGFR4</i>, <i>CYP7A1</i>, <i>FOS</i>, and <i>EGR1</i> in HUH7 xenograft tumors from Fig. 5B. <i>D</i>, Multiple, large, raised tumors (arrows) protruding from the hepatic surface of a DEN-accelerated FGF19-TG:FGFR4-WT mouse treated with a control antibody (upper panel). Liver of DEN-accelerated FGF19-TG:FGFR4-WT mouse treated with LD1 (lower panel). <i>E</i>, Liver weights of DEN–accelerated FGF19-TG:FGFR4-WT mice treated with control antibody, LD1, or 1A6 (anti-FGF19 antibody).</p

LD1 inhibits FGFR4 activities.

<p><i>A</i>, LD1 inhibits FGFR4 binding to FGF1 and FGF19 as determined by solid phase binding assay. <i>B</i>, LD1 inhibits FGF1-stimulated proliferation of BaF3 cells stably expressing FGFR4/R1. <i>C</i>, LD1 inhibits FGFR4 signaling in L6 cells stably expressing FGFR4. <i>D</i>, Cell surface expression of FGFR4 protein in a subset of liver tumor cell lines as determined by FACS analysis using LD1.</p

LD1 inhibits FGFR4 biological activities in liver cancer cell lines.

<p><i>A</i>, LD1 inhibits FGFR4 signaling in HEP3B cells as evaluated by Western blot. <i>B</i>, LD1 inhibits the FGFR4-regulated <i>CYP7A1</i> repression in HEP3B cells. <i>CYP7A1</i> levels are represented as fold expression relative to the level in untreated cells. <i>C</i>, LD1 inhibits FGFR4-regulated <i>FOS</i> expression in a panel of liver cancer cell lines. The results are represented as fold expression relative to the <i>FOS</i> level in untreated cells. <i>D</i>, Inhibition of colony formation by repression of FGFR4 expression in JHH5 cells stably transfected with an FGFR4 shRNA doxycycline-inducible vector. <i>E</i>, Enumeration of LD1-inhibited liver cancer cell line colony formation. The values are represented as percent of the number of colonies enumerated in the absence of added LD1. <i>F</i>, LD1 inhibits HCC cell line colony formation.</p

LD1 binds to FGFR4.

<p><i>A</i>, LD1 binds to human (h), mouse (m), and cynomolgus monkey (c) FGFR4, but does not bind to hFGFR1, hFGFR2, or hFGFR3. The binding of LD1 to immobilized FGFR-Fc chimeric proteins was determined by solid phase binding assay. <i>B</i>, Affinity of LD1 binding to mouse, cynomolgus monkey, and human FGFR4 as determined by surface plasmon resonance. <i>C</i>, Binding of LD1 to hFGFR4 expressed at the cell surface of stably transfected HEK293 cells as measured by FACS (RFU  =  Relative Fluorescence Unit). <i>D</i>, The binding of LD1 to immobilized hFGFR4-Flag chimeric proteins bearing point mutations as measured by a solid phase binding assay. <i>E</i>, The binding of LD1 to hFGFR4-Flag chimeric proteins bearing point mutations as evaluated by Western blot. Mutated proteins were electrophoresed and sequentially immunoblotted using LD1, an anti-FGFR4 (8G11), and an anti-Flag antibody. <i>F</i>, Dimer model illustrating the position of G165 (blue) on FGFR4 (red and yellow) bound to FGF19 (green).</p