Mailing not saved, must cleanup caches to be able to save again
Because mosaico uses the new-ish afform form tools (i.e. an integration of AngularJS), it means that a lot of the communication from the form to the server is happening via ajax. When that back-channel communication fails, that's when you get that message.
Possible reasons for the failure include:

The same form open in a different window (leading to invalid state data being sent to the server).
A network problem between your window and the server.
A server error due to a bug.
A server non-response due to a delay.

Your solution will depend on diagnosing which of these is going on, using:

Your browser developer tools network tab and console.
Your civicrm, CMS and server logs.

A lot of the time, you may get that message without it meaning anything terrible and it can be ignored, but usually you want to try an explicit save at that point and then check the civicrm server logs for errors.
For example, I have a client out in the country using a satellite-based ISP, and she regularly has this issue - not much to do except wait for the cloud to stop blocking the satellite ...