In the sentence extracted from biomedical literature, identify all the chemical entities. The required answer format is the same sentence with HTML <span> tags to mark up specific entities. 
### Entity Markup Guides:
Use <span class="chemical"> to denote a chemical.

### Input Text: Treatment with E2 , however , failed to prevent these increases at the mRNA level .
### Output Text:
Treatment with <span class="chemical">E2</span> , however , failed to prevent these increases at the mRNA level . 