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Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination.

Neuromolecular Med

January 2025

Department of Anatomy, School of Basic Medical Sciences, Shanxi Medical University, No 56, Xinjian Nan Road, Taiyuan, 030001, Shanxi, China.

The integrity of the myelin sheath of the spinal cord (SC) is essential for motor coordination. Seipin is an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue and motor neurons in the SC. It was reported Seipin deficiency induced lipid dysregulation and neurobehavioral deficits, but the underlying mechanism, especially in SC, remains to be elucidated.

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Wnt7a-Cre is a commonly used for generating uterine epithelial conditional knockout mice, such as epiERα-/- (Esr1f/-Wnt7aCre/+) and epiPR-/- (Pgrf/-Wnt7aCre/+). We noticed that epiERα-/- females, but not epiPR-/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle.

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Design of ROS-Triggered Sesquiterpene Lactone SC Prodrugs as TrxR1 Covalent Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

J Med Chem

January 2025

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.

Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.

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Background: IgE-mediated food allergy is accompanied by mucosal mast cell (MMC) hyperplasia in the intestinal mucosa. Intestinal MMC numbers correlate with the severity of food allergy symptoms. However, the mechanisms by which MMCs proliferate excessively are poorly understood.

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TBC1D20 coordinates vesicle transport and actin remodeling to regulate ciliogenesis.

J Cell Biol

April 2025

Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

TBC1D20 deficiency causes Warburg Micro Syndrome in humans, characterized by multiple eye abnormalities, severe intellectual disability, and abnormal sexual development, but the molecular mechanisms remain unknown. Here, we identify TBC1D20 as a novel Rab11 GTPase-activating protein that coordinates vesicle transport and actin remodeling to regulate ciliogenesis. Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells.

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