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Pre-Blend Weekly Schedule Example Pre-blend dose at each titration step Phase Start Weeks 1-4 Draw Volume 0.40 mL (40 units) Reta Delivered 2.0 mg Cag Delivered 0.4 mg Phase Step 1 Weeks 5-8 Draw Volume 0.60 mL (60 units) Reta Delivered 3.0 mg Cag Delivered 0.6 mg Phase Step 2 Weeks 9-16 Draw Volume 0.80 mL (80 units) Reta Delivered 4.0 mg Cag Delivered 0.8 mg Phase Step 3 Weeks 17-20 Draw Volume 1.20 mL (120 units) Reta Delivered 6.0 mg Cag Delivered 1.2 mg Phase Step 4 Weeks 21-24 Draw Volume 1.60 mL (160 units) Reta Delivered 8.0 mg Cag Delivered 1.6 mg Phase Maintenance Weeks 25+ Draw Volume 2.40 mL (240 units) Reta Delivered 12.0 mg Cag Delivered 2.4 mg One injection per week

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In the co-culture system, MCECs derived from the model group exhibited significant reduced ZO-1 and Occludin expression compared to those from the Control group, whereas GHK-Cu elevated theses protein levels (Figures 4GI)

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