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Neuroprotective Effects, Mechanisms of Action and Therapeutic Potential of the Kv7/KCNQ Channel Opener QO-83 in Ischemic Stroke.
Transl Stroke Res
January 2025
Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential.
View Article and Find Full Text PDFSynergistic Enhancement of Ferroptosis via Mitochondrial Accumulation and Photodynamic-Controlled Release of an Organogold(I) Cluster Prodrug.
J Am Chem Soc
January 2025
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.
Effective delivery and controlled release of metallo-prodrugs with sustained activation and rapid response feed the needs of precise medicine in metal chemotherapeutics. However, gold-based anticancer drugs often suffer from detoxification binding and extracellular transfer by sulfur-containing peptides. To address this challenge, we integrate a thiol-activated prodrug strategy of newly prepared hypercoordinated carbon-centered gold(I) clusters (HCGCs) with their photosensitization character to augment the mitochondrial release of Au(I) in tumors.
View Article and Find Full Text PDFDaily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism.
iScience
January 2025
Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA.
Alterations to the excitation/inhibition (E/I) ratio are postulated to underlie behavioral phenotypes in autism spectrum disorder (ASD) patients and mouse models. However, in wild type mice the E/I ratio is not constant, but instead oscillates across the 24-h day. Therefore, we tested whether E/I regulation, rather than the overall E/I ratio, is disrupted in two ASD-related mouse lines: KO and BTBR, models of syndromic and idiopathic ASD, respectively.
View Article and Find Full Text PDFSpatiotemporal network dynamics and structural correlates in the human cerebral cortex in vitro.
Prog Neurobiol
January 2025
Institute of Biomedical Investigations August Pi i Sunyer (IDIBAPS), Systems Neuroscience, 08036 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain. Electronic address:
Elucidating human cerebral cortex function is essential for understanding the physiological basis of both healthy and pathological brain states. We obtained extracellular local field potential recordings from cortical slices of neocortical tissue from refractory epilepsy patients. Multi-electrode recordings were combined with histological information, providing a two-dimensional spatiotemporal characterization of human cortical dynamics in control conditions and following modulation of the excitation/inhibition balance.
View Article and Find Full Text PDFMolecular glue for phycobilisome attachment to photosystem II in sp. PCC 7002.
Proc Natl Acad Sci U S A
January 2025
State Key Laboratory of Protein and Plant Genetic Engineering, School of Life Science, Peking University, Beijing 100871, People's Republic of China.
Phycobilisomes (PBS) are the major photosynthetic light-harvesting complexes in cyanobacteria and red algae. While the structures of PBS have been determined in atomic resolutions, how PBS are attached to the reaction centers of photosystems remains less clear. Here, we report that a linker protein (LcpA) is required for the attachment of PBS to photosystem II (PSII) in the cyanobacterium sp.
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