I was trying to make a long explanation, but I found it would be too confusing. I hope this will help, but if you have more questions, let me know.
"De por sí" describes an intrinsic feature of something or someone and you have something to add:
- Ya de por sí me aburro en casa; ahora es peor con el confinamiento.
I already get awfully bored at home; now it's worse because of the lockdown.
- Juan de por sí es medio alcohólico y luego lo invitas a tomar... *insert roll eye emoji*
Juan is pretty much an alcoholic, and you're taking him out to drink. (Implicit question, what is wrong with you?)
- Estoy muy desvelado y tengo examen de química. Si la materia es de por sí difícil, voy a reprobar.
I haven't slept and I have a chemistry test. I'll fail since the subject is already hard by itself.
- Las últimas elecciones vinieron a complicar más la situación del país, que era de por sí delicada.
The last elections made the situation of the country even more complicated than it was.
- Al negocio de por sí le estaba yendo mal. Ahora con el asalto, tuvimos que cerrar.
Our business was already in trouble and after having been robbed, we had to close it down.
"Por sí solo" may have a similar use, but the structure of the sentence has to change a little:
- El hecho de que me aburro mucho en casa por sí solo ya era un problema para mí. Ahora, con el confinamiento, es peor.
The fact that I get bored at home is already a big problem for me. Now, with the lockdown is worse.
- El alcoholismo de Juan es grave por sí solo. No necesitas invitarlo a tomar para hacerlo peor.
Juan's alcoholism is already bad per se. You don't need to take him out to drink and make it worse.
- Estoy desvelado y tengo examen de química. Si la materia es por sí sola difícil, voy a reprobar.
I haven't slept and I have a chemistry exam. Since the subject is hard per se, I'm failing.
- La situación del negocio ya era mala por sí sola. Después del asalto, tuvimos que cerrar.
The business situation was already bad itself, but after the robbery we had to close it down.
And "por sí solo" may also mean to do something by one's own means:
- Los médicos no pueden parar la epidemia por sí solos. Necesitamos ayudarlos.
The doctors can't stop the epidemic by themselves. We need to help them.
- Roberto dice que puede salir adelante por sí solo. Ya veremos.
Roberto says he can be successful by his own means. We'll see about that.
- La escuela, por sí sola, no es suficiente para educar a los hijos.
The school by itself is not enough to educate our children.
- El exoesqueleto ayuda a ponerse de pie a las personas que no pueden hacerlo por sí solas.
The exoskeleton helps to stand up the people who can't do it by themselves.