Water-soluble platinum and palladium porphyrins with peripheral ethyl phosphonic acid substituents: synthesis, aggregation in solution, and photocatalytic properties.

Water-soluble porphyrins have garnered significant attention due to their broad range of applications in biomedicine, catalysis, and material chemistry. In this work, water-soluble platinum(II) and palladium(II) complexes with porphyrins bearing ethyl phosphonate substituents, namely, Pt/Pd 10-(ethoxyhydroxyphosphoryl)-5,15-di(-carboxyphenyl)porphyrins (M3m, M = Pt(II), Pd(II)) and Pt/Pd 5,10-bis(ethoxyhydroxyphosphoryl)-10,20-diarylporphyrins (M1d-M3d; aryl = -tolyl (1), mesityl (2), -carboxyphenyl (3)), were synthesized by alkaline hydrolysis of the corresponding diethyl phosphonates M6m and M4d-M6d. NMR, UV-vis, and fluorescence spectroscopy revealed that the mono-phosphonates M3m tend to form aggregates in aqueous media, while the bis-phosphonates M3d exist predominantly as monomeric species across a wide range of concentrations (10-10 M), ionic strengths (0-0.

The association of high-density lipoprotein cargo proteins with brain volume in older adults in the Atherosclerosis Risk in Communities (ARIC).

Background: High-density lipoprotein (HDL) modulates the blood-brain barrier and cerebrovascular integrity, likely influencing the risk of Alzheimer's disease (AD), neurodegeneration, and cognitive decline.

Objective: This study aims to identify HDL protein cargo associated with brain amyloid deposition and brain volume in regions vulnerable to AD pathology in older adults.

Methods: HDL was separated from the plasma of 65 non-demented participants of the Atherosclerosis Risk in Communities (ARIC) study using a fast protein liquid chromatography method.

Reversal of Endothelial Cell Anergy by T Cell-Engaging Bispecific Antibodies.

Reduced expression of adhesion molecules in tumor vasculature can limit infiltration of effector T cells. To improve T cell adhesion to tumor endothelial cell (EC) antigens and enhance transendothelial migration, we developed bispecific, T-cell engaging antibodies (bsAb) that activate T cells after cross-linking with EC cell surface antigens. Recombinant T-cell stimulatory anti-VEGFR2-anti-CD3 and costimulatory anti-TIE2-anti-CD28 or anti-PD-L1-anti-CD28 bsAb were engineered and expressed.

Concerted or Stepwise? An Experimental and Computational Study to Reveal the Mechanistic Change as a Result of the Substituent Effects.

This study investigates the Cope elimination reaction, focusing on the mechanistic shift between concerted and stepwise pathways influenced by substituent effects. Experimental approaches, including kinetic isotope effects (KIEs) and linear free energy relationships (LFERs), alongside density functional theory (DFT) computations, were employed to explore the influence of substituents on the reaction kinetics and pathways. Our findings reveal temperature- and substituent-dependent partitioning between the concerted syn-β elimination and the stepwise E1cB mechanism, providing deeper insights into the mechanistic diversity of elimination reactions.

Safety and tolerability of the M2 muscarinic acetylcholine receptor modulator BAY 2413555 in heart failure with reduced ejection fraction in the REMOTE-HF study.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.