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In-Cell Mass Spectrometry and Ultraviolet Photodissociation Navigates the Intracellular Protein Heterogeneity.
J Am Chem Soc
January 2025
State Key Laboratory of Molecular Reaction Dynamics, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Directly probing the heterogeneous conformations of intracellular proteins within their native cellular environment remains a significant challenge in mass spectrometry (MS). Here, we establish an in-cell MS and ultraviolet photodissociation (UVPD) strategy that directly ejects proteins from living cells into a mass spectrometer, followed by 193 nm UVPD for structural analysis. Applying this approach to calmodulin (CaM), we reveal that it adopts more extended conformations within living cells compared with purified samples , highlighting the unique influence of intracellular environments on protein folding.
View Article and Find Full Text PDFInactivation of CaV1 and CaV2 channels.
J Gen Physiol
March 2025
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression.
View Article and Find Full Text PDFUnderstanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.
Acta Neuropathol Commun
January 2025
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFExosomal miR-122 derived from M2 macrophages induces osteogenic differentiation of bone marrow mesenchymal stem cells in the treatment of alcoholic osteonecrosis of the femoral head.
J Orthop Surg Res
January 2025
Department of Joint Osteopathy, Liuzhou Worker's Hospital, Liuzhou, Guangxi Province, 545000, China.
Alcoholic osteonecrosis of the femoral head (AIONFH) is caused by long-term heavy drinking, which leads to abnormal alcohol and lipid metabolism, resulting in femoral head tissue damage, and then pathological necrosis of femoral head tissue. If not treated in time in clinical practice, it will seriously affect the quality of life of patients and even require hip replacement to treat alcoholic femoral head necrosis. This study will confirm whether M2 macrophage exosome (M2-Exo) miR-122 mediates alcohol-induced BMSCs osteogenic differentiation, ultimately leading to the inhibition of femoral head necrosis.
View Article and Find Full Text PDFWireless Stimulation of Barium Titanate@PEDOT Nanoparticles Toward Bioelectrical Modulation in Cancer.
ACS Appl Mater Interfaces
January 2025
Department of Bioengineering and iBB - Institute of Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisbon 1049-001, Portugal.
Cancer cells possess distinct bioelectrical properties, yet therapies leveraging these characteristics remain underexplored. Herein, we introduce an innovative nanobioelectronic system combining a piezoelectric barium titanate nanoparticle core with a conducting poly(3,4-ethylenedioxythiophene) shell (BTO@PEDOT NPs), designed to modulate cancer cell bioelectricity through noninvasive, wireless stimulation. Our hypothesis is that acting as nanoantennas, BTO@PEDOT NPs convert mechanical inputs provided by ultrasound (US) into electrical signals, capable of interfering with the bioelectronic circuitry of two human breast cancer cell lines, MCF-7 and MDA-MB-231.
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