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Ethics declarations Ethics approval and consent to participate The animal study was reviewed and approved by Experimental Animal Center of Wenzhou Medical University (Approval ID: wydw2022-0032)

88 Single-cell proteomics, which quantifies protein expression and pathway activation at single-cell resolution, reveals functional heterogeneity, dynamic regulation of resistance-associated proteins, and their interactions with the TME

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However, more consistent results may be observed with regular use over several days

Additional water-mediated hydrogen bonding between PDE1B inhibitors (e.g., pyrazolo-pyrimidone and quinazoline cores) and residues such as Q421, Y222, and H373 further enhances binding affinity

Oxidized Glutathione 9.2