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Preferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.
J Phys Chem B
January 2025
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.
View Article and Find Full Text PDFCreating Glepaglutide, the First Long-Acting GLP-2 Analogue to Enable a Ready-to-Use Injection.
J Med Chem
January 2025
Zealand Pharma A/S, Sydmarken 11, 2860 Søborg, Denmark.
Human glucagon-like peptide-2 (hGLP-2) receptor agonists have a benefit for the treatment of short bowel syndrome (SBS) and potentially other intestinal diseases (e.g., IBD).
View Article and Find Full Text PDFIQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice.
Cell Commun Signal
January 2025
Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, 400010, China.
Background: Asthenozoospermia (ASZ) accounts for about 20-40% of male infertility, and genetic factors, contributing to 30-40% of the causes of ASZ, still need further exploration. Radial spokes (RSs), a T-shaped macromolecular complex, connect the peripheral doublet microtubules (DMTs) to a central pair (CP), forming a CP-RS-DMT structure to regulate the beat frequency and amplitude of sperm flagella. To date, many components of RSs and their functions in human sperm flagella remain unclear.
View Article and Find Full Text PDFTransanal vs Laparoscopic Total Mesorectal Excision and 3-Year Disease-Free Survival in Rectal Cancer: The TaLaR Randomized Clinical Trial.
JAMA
January 2025
Department of General Surgery (Colorectal Surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Importance: Previous studies have demonstrated the advantages of short-term histopathological outcomes and complications associated with transanal total mesorectal excision (TME) compared with laparoscopic TME. However, the long-term oncological outcomes of transanal TME remain ambiguous. This study aims to compare 3-year disease-free survival of transanal TME with laparoscopic TME.
View Article and Find Full Text PDFNewly synthesized proteins destined for the secretory pathway are folded and assembled in the endoplasmic reticulum (ER) and then transported to the Golgi apparatus via COPII vesicles, which are normally 60-90 nm. COPII vesicles must accordingly be enlarged to accommodate proteins larger than 90 nm, such as long-chain collagen. Key molecules involved in this enlargement are Tango1 and Tango1-like (Tali), which are transmembrane proteins in the ER encoded by the MIA3 and MIA2 genes, respectively.
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