TL;DR: Back up your 3dn files and make multiple successive backups with your progress.
Some of you may have had the misfortune of closing out 3DNes and coming back to find out your 3dn file will no longer load, because it was corrupted somehow.
This has happened to me twice already with Mega Man 2, at some point after setting the 5th Robot Master stage (I did the same five both times but in a different order). The 3dn files both times they failed were somewhere around 13.4 MB, and so I thought this was a file size issue. However, my Mega Man 1 file I uploaded works correctly at over 15 MB.
Moments ago I was in my third attempt to set MM2 from scratch, now using 3DNes 1.1b1. This time I saved a backup after completing each Robot Master by copying the .3dn and .bak files to another folder. I successfully got through the fourth RM (two of the same RMs from before, two new), but any attempt to modify any new objects caused the 3dn and the bak file to fail, so I could not even begin the 5th. My thought is that the 3dn file may become corrupted after a threshold number of objects are modified. It's true that MM1's 3dn file was bigger, but I think I can honestly say I've modified far more objects in one-third of MM2 than in the entirety of MM1.
What this means for you is that you should save unique backups after modest amounts of work so that you can roll back to the last working version just in case. Also make sure that after you witness a corruption, you close out of the program without opening any other roms, just in case the corruption carries over, which I have seen happen.
I've sent geod a link to the working 3dn file for him to look at. Work with caution, everyone.