Ellis, here is my best guess about what’s happening. It appears that your Red layer is a pixel layer. In other words, your Red layer is an image created from the low res guide image. When you up-size the guide file, you also up-size the Red layer. Both layers show interpolation artifacts. When you later bring in your original image, it has no effect on the Red layer since it no longer is dependent on the layers beneath it in your layer stack. For example, even before you bring in your original layer, modifying your background layer will not change your Red layer. (The overall image may change, reflecting the change to the background layer, but the Red layer itself won’t change.)
If I’m correct, then you’ll need to re-do your Red layer. In other words, in your example, put your original image, layer 1, just above the Red layer (other layers such as your curves layer should be above Layer 1). Now, create a new Red layer above layer 1 using the same settings you used to make the original Red layer, but your Apply Image should apply layer 1, not the background layer. At this point, you can delete the original Red layer and the background layer. If you later want to use a PS plug-in that requires a background layer, such as PhotoKit Sharpener, you can rename your layer 1 as Background (at least this trick works for PhotoKit Sharpener).
Instead of dragging your original into your up-sized guide file, you could drag your non-pixel, up-sized adjustment layers onto your original, if it suits you needs better. (Note Andrew Rodney’s comment above if you don’t have masks.) Of course, you’d still need to recreate your other pixel based adjustment layers.