Described are ligand-directed catalysts for live-cell, photocatalytic activation of bioorthogonal chemistry. Catalytic groups are localized via a tethered ligand either to DNA or to tubulin, and red light (660 nm) photocatalysis is used to initiate a cascade of DHTz oxidation, intramolecular Diels−Alder reaction, and elimination to release phenolic compounds. Silarhodamine (SiR) dyes, more conventionally used as biological fluorophores, serve as photocatalysts that have high cytocompatibility and produce minimal singlet oxygen. Commercially available conjugates of Hoechst dye (SiR-H) and docetaxel (SiR-T) are used to localize SiR to the nucleus and microtubules, respectively. Computation was used to assist the design of a new class of redox-activated photocage to release either phenol or n-CA4, a microtubule-destabilizing agent. In model studies, uncaging is complete within 5 min using only 2 μM SiR and 40 μM photocage. In situ spectroscopic studies support a mechanism involving rapid intramolecular Diels−Alder reaction and a rate-determining elimination step. In cellular studies, this uncaging process is successful at low concentrations of both the photocage (25 nM) and the SiR-H dye (500 nM). Uncaging n-CA4 causes microtubule depolymerization and an accompanying reduction in cell area. Control studies demonstrate that SiR-H catalyzes uncaging inside the cell, and not in the extracellular environment. With SiR-T, the same dye serves as a photocatalyst and the fluorescent reporter for microtubule depolymerization, and with confocal microscopy, it was possible to visualize microtubule depolymerization in real time as the result of photocatalytic uncaging in live cells.
What is already known about this topic?Hematological parameters may indicate the presence of chronic low-grade inflammation and increasing viscosity, which are involved in the pathological processes of gestational diabetes mellitus (GDM). However, the association between several hematological parameters in early pregnancy and GDM has yet to be elucidated.
What is added by this report?Hematological parameters in the first trimester, particularly red blood cell (RBC) count and systematic immune index, have a significant impact on GDM incidence. The neutrophils (NEU) count in the first trimester was particularly pronounced for GDM. The upward trend of RBC, white blood cell (WBC), and NEU counts was consistent across all GDM subtypes. What are the implications for public health practice? Early pregnancy hematological parameters are associated with the risk of GDM.
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