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Role of Virtual Ruler-Based Diameter Measurement in Endoscopic Therapy for Cirrhotic Esophageal Varices: A Retrospective Multicenter Study.
Can J Gastroenterol Hepatol
December 2024
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230001, China.
Esophageal variceal (EV) diameter is a critical, independent risk factor for hemorrhage, and plays a key role in guiding choices of endoscopic treatment techniques. We developed a novel tool, the virtual ruler (VR), which offers increased precision and expediency in EV diameter (EVD) measurements. This study investigates the clinical value of VR for assessing EVD during the endoscopic treatment of cirrhotic EVs.
View Article and Find Full Text PDFPromotion of RNF168-Mediated Nucleosomal H2A Ubiquitylation by Structurally Defined K63-Polyubiquitylated Linker Histone H1.
Angew Chem Int Ed Engl
January 2025
New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry, Tsinghua University, Beijing, 100084, China.
The chemical synthesis of histones with homogeneous modifications is a powerful approach for quantitatively deciphering the functional crosstalk between different post-translational modifications (PTMs). In this study, we developed an expedient site-specific (poly)ubiquitylation strategy (CAEPL, Cysteine Aminoethylation coupled with Enzymatic Protein Ligation), which integrates the Cys-aminoethylation reaction with the process of ubiquitin-activating enzyme UBA1-assisted native chemical ligation. Using this strategy, we successfully prepared monoubiquitylated and K63-linked di- and tri-ubiquitylated linker histone H1.
View Article and Find Full Text PDFModular access to alkylgermanes via reductive germylative alkylation of activated olefins under nickel catalysis.
Nat Commun
November 2023
School of Chemistry and Materials Science, Institute of Advanced Materials and Flexible Electronics (IAMFE), Nanjing University of Information Science and Technology, 219 Ningliu Road, Nanjing, 210044, China.
Carbon-introducing difunctionalization of C-C double bonds enabled by transition-metal catalysis is one of most straightforward and efficient strategies to construct C-C and C-X bonds concurrently from readily available feedstocks towards structurally diverse molecules in one step; however, analogous difunctionalization for introducing germanium group and other functionalities remains elusive. Herein, we describe a nickel-catalyzed germylative alkylation of activated olefins with easily accessible primary, secondary and tertiary alkyl bromides and chlorogermanes as the electrophiles to form C-Ge and C-C bonds simultaneously. This method provides a modular and facile approach for the synthesis of a broad range of alkylgermanes with good functional group compatibility, and can be further applied to the late-stage modification of natural products and pharmaceuticals, as well as ligation of drug fragments.
View Article and Find Full Text PDFLate-stage C-H Functionalization of Tryptophan-Containing Peptides with Thianthrenium Salts: Conjugation and Ligation.
Angew Chem Int Ed Engl
February 2023
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammanstrasse 2, 37077, Göttingen, Germany.
Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging, among other applications. Herein, we report on a palladium-catalyzed C-H arylation of tryptophan-containing peptides with readily accessible and modular arylthianthrenium salts. Under exceedingly mild reaction conditions, the late-stage diversification of structurally complex peptides was accomplished.
View Article and Find Full Text PDFChemical Synthesis of Post-Translationally Modified H2AX Reveals Redundancy in Interplay between Histone Phosphorylation, Ubiquitination, and Methylation on the Binding of 53BP1 with Nucleosomes.
J Am Chem Soc
October 2022
Department of Chemistry, Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China.
The chemical synthesis of homogeneously modified histones is a powerful approach to quantitatively decipher how post-translational modifications (PTMs) modulate epigenetic events. Herein, we describe the expedient syntheses of a selection of phosphorylated and ubiquitinated H2AX proteins in a strategy integrating expressed protein hydrazinolysis and auxiliary-mediated protein ligation. These modified H2AX proteins were then used to discover that although H2AXS139 phosphorylation can enhance the binding of the DNA damage repair factor 53BP1 to either an unmodified nucleosome or that bearing a single H2AXK15ub or H4K20me2 modification, it augments 53BP1's binding only weakly to nucleosomes bearing both H2AXK15ub and H4K20me2.
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