Structural and molecular basis of choline uptake into the brain by FLVCR2.

Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification, and neurotransmission. The brain has a particularly high demand for choline, but how it enters the brain has eluded the field for over fifty years. The MFS transporter FLVCR1 was recently determined to be a choline transporter, and while this protein is not highly expressed at the blood-brain barrier (BBB), its relative FLVCR2 is. Previous studies have shown that mutations in human Flvcr2 cause cerebral vascular abnormalities, hydrocephalus, and embryonic lethality, but the physiological role of FLVCR2 is unknown. Here, we demonstrate both in vivo and in vitro that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain. We also determine the structures of choline-bound FLVCR2 in the inward- and outward-facing states using cryo-electron microscopy to 2.49 and 2.77 Å resolution, respectively. These results reveal how the brain obtains choline and provide molecular-level insights into how FLVCR2 binds choline in an aromatic cage and mediates its uptake. Our work could provide a novel framework for the targeted delivery of neurotherapeutics into the brain.

Long-Chain Branched Bio-Based Poly(butylene dodecanedioate) Copolyester Using Pentaerythritol as Branching Agent: Synthesis, Thermo-Mechanical, and Rheological Properties.

The introduction of long-chain branched structures into biodegradable polyesters can effectively improve the melt strength and blow-molding properties of polyesters. In this study, pentaerythritol (PER) was used as a branching agent to synthesize branched poly(butylene dodecanedioate) (PBD), and the resulting polymers were characterized by Nuclear Magnetic Resonance Proton Spectra (1H NMR) and Fourier Transform Infrared spectroscopy (FT-IR). It was found that the introduction of a small amount of PER (0.25-0.5 mol%) can generate branching and even crosslinking structures. Both impact strength and tensile modulus can be greatly improved by the introduction of a branching agent. With the introduction of 1 mol% PER content in PBD, the notched impact strength of PBD has been increased by 85%, and the tensile modulus has been increased by 206%. Wide-angle X-ray diffraction and differential scanning calorimetry results showed that PER-branched PBDs exhibited improved crystallization ability compared with linear PBDs. Dynamic viscoelastics revealed that shear-thickening behaviors can be found for all branched PBD under low shear rates.