Dynamic single cell transcriptomics defines kidney FGF23/KL bioactivity and novel segment-specific inflammatory targets.

Fibroblast growth factor 23 (FGF23) via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in both rare and very common syndromes. However, the spatial-temporal mechanisms dictating kidney FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic.

Photodegradable polyacrylamide tanglemers enable spatiotemporal control over chain lengthening in high-strength and low-hysteresis hydrogels.

Covalent hydrogel networks suffer from a stiffness-toughness conflict, where increased crosslinking density enhances the modulus of the material but also leads to embrittlement and diminished extensibility. Recently, strategies have been developed to form highly entangled hydrogels, colloquially referred to as tanglemers, by optimizing polymerization conditions to maximize the density and length of polymer chains and minimize the crosslinker concentration. It is challenging to assess entanglements in crosslinked networks beyond approximating their theoretical contribution to mechanical properties; thus, in this work, we synthesize and characterize polyacrylamide tanglemers using a photolabile crosslinker, which allows for direct assessment of covalent trapping of entanglements under tension.

Photochemical Control of Network Topology in PEG Hydrogels.

Hydrogels are often synthesized through photoinitiated step-, chain-, and mixed-mode polymerizations, generating diverse network topologies and resultant material properties that depend on the underlying network connectivity. While many photocrosslinking reactions are available, few afford controllable connectivity of the hydrogel network. Herein, a versatile photochemical strategy is introduced for tuning the structure of poly(ethylene glycol) (PEG) hydrogels using macromolecular monomers functionalized with maleimide and styrene moieties.

Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets.

Unlabelled: FGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes, however the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution.

Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.

Background: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear.

Methods: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects.