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SummaryChemical biology methods such as high-throughput screening (HTS) and affinity-based target identification can be used to probe biological systems on a biomacromolecule level, providing valuable insights into the molecular mechanisms of those systems. Here, by establishing a human embryonal carcinoma cell-based HTS platform, we screened 171,077 small molecules for regulators of pluripotency and identified a small molecule, Displurigen, that potently disrupts hESC pluripotency by targeting heat shock 70-kDa protein 8 (HSPA8), the constitutively expressed member of the 70-kDa heat shock protein family, as elucidated using affinity-based target identification techniques and confirmed by loss-of-function and gain-of-function assays. We demonstrated that HSPA8 maintains pluripotency by binding to the master pluripotency regulator OCT4 and facilitating its DNA-binding activity.

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Variceal bleeding is a life-threatening complication of portal hypertension. In recent years, transjugular intrahepatic portosystemic shunt (TIPS) creation has cemented a role in the management of acute refractory bleeding and recurrent variceal hemorrhage. This article aims to review the use of TIPS in patients with variceal bleeding, with a focus on accepted procedure indications, patient selection criteria, TIPS technique, clinical outcomes, and contemporary issues, such as early TIPS in acute variceal hemorrhage, the role of adjuvant embolotherapy, and TIPS utility for gastric varices.