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https://www.selleckchem.com/products/px-12.html ic early adolescents.Background STAT3 is a pro-oncogenic transcription factor. Pyrimethamine (PYM) is a STAT3 inhibitor that suppresses the proliferation of some cancer cells through downregulation of STAT3 target proteins. Methodology & Results We have used structure-based tools to design novel PYM-based compounds. Intracellular target validation studies revealed that representative compounds 11b-d and 15a downregulate STAT3 downstream proteins and inhibit STAT3 DNA binding domain (DBD). Relative to PYM, a cohort of these compounds are >100-fold more cytotoxic to cancer cells with constitutively active (high pSTAT3) and basal (low pSTAT3) STAT3 signaling, suggesting that STAT3 DBD inhibition is deleterious to the proliferation of cancer cells with low and high pSTAT3 levels. Conclusion These are promising leads for further preclinical evaluation as therapeutic agents for STAT3-dependent cancers. To explore the possible challenges and difficulties of using Personal Protective Equipment (PPE) in ophthalmic practice during the Coronavirus disease 2019 (COVID-19) pandemic. This is a multicenter, international survey among practicing ophthalmologists across different countries. The survey was conducted from September 9th to October 24th, 2020. It included a total of 23 questions that navigated through the currently adopted recommendations in different clinical situations. The survey also assessed the convenience of using various PPE in ophthalmic practice and addressed the clarity of the examination field while using various PPE during clinical or surgical procedures. One hundred and seventy-two ophthalmologists completed the survey (101 from Egypt, 50 from the USA, and 21 from four other countries). The analysis of the responses showed that most ophthalmologists use face masks without significant problems during their examinations, while face shields followed by protective goggles were the most inconvenient PPE in the cur

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