T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

BACKGROUND: Silk fibroin blend films with α-helix cannot be used as biomaterials due to water-soluble and unstable; however, β-sheet structure is stable. OBJECTIVE: To prepare for a β -sheet conformation silk fibroin composite films mixing fucoidan and to observe the physical and chemical characteristics of silk fibroin/fucoidan composite films. DESIGN, TIME AND SETTING: The physical and chemical characteristics experiments of silk fibroin/fucoidan composite films were conducted in Chemistry Experiment Center of Institute of Chemistry Chinese Academy of Sciences and Chengde Petroleum College from November 2003 to August 2006. MATERIALS: Fucoidan was isolated from Laminaria Japonica, and Bombyx mori silk was commercially from China Import & Export Company. METHODS: The solution prepared with a different blend ratios aqueous solution of silk fibroin and fucoidan, was cast into apolystyrene plate and incubated at 25 ℃ and 65% relative humidity. Silk fibroin film was formed after dry the plate at the temperature. The composite films were well when the mixing rate of fucoidan was more than 20% (w). The silk fibroin solution and fucoidan solution were mixed according to the different mass ratios of silk fibroin and fucoidan, including 0∶100, 5∶95, 10∶90, 20:80, and 100∶0. The films were marked a, b, c, d and e, respectively. MAIN OUTCOME MEASURES: The physical and chemical characteristics of silk fibroin/fucoidan composite films were examined through Fourier transform infrared spectroscopy, X-rey diffractometry, and thermogravimetry. RESULTS: The conformation of silk fibroin in blend films was revealed to be β-sheet structure according to the results of Fourier transform infrared and X-ray diffractometry spectra. These results demonstrated that the conformation change of silk fibroin occurred from a random coil to a β-sheet structure due to the formation of intermolecular hydrogen bonds between fucoidan and silk fibroin in the blend films. Thermogravimetry showed that the crystalline silk fibroin films had higher thermal stability than the amorphous silk fibroin film. CONCLUSION: The conformation of silk fibroin in composite films was revealed to be a β -sheet structure according to the results of Fourier transform infrared and X-ray diffractometry spectra. The crystalline silk fibroin films showed higher thermal stability than the amorphous silk fibroin film.