The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation.

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1).

Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination.

An enhanced biophysical screening strategy to investigate the affinity of ASOs for their target RNA.

The recent and rapid increase in the discovery of new RNA therapeutics has created the perfect terrain to explore an increasing number of novel targets. In particular, antisense oligonucleotides (ASOs) have long held the promise of an accelerated and effective drug design compared to other RNA-based therapeutics. Although ASOs design has advanced distinctively in the past years, especially thanks to the several predictive frameworks for RNA folding, it is somehow limited by the wide approximation of calculating sequence affinity based on RNA-RNA/DNA sequences.

Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function.

In terms of lipid nanoparticle (LNP) engineering, the relationship between particle composition, delivery efficacy, and the composition of the biocoronas that form around LNPs, is poorly understood. To explore this we analyze naturally efficacious biocorona compositions using an unbiased screening workflow. First, LNPs are complexed with plasma samples, from individual lean or obese male rats, and then functionally evaluated in vitro.

Solution and Membrane Interaction Dynamics of Fatty Acyl-CoA Synthetase FadD13.

The very-long-chain fatty acyl-CoA synthetase FadD13 from activates fatty acids for further use in mycobacterial lipid metabolism. FadD13 is a peripheral membrane protein, with both soluble and membrane-bound populations . The protein displays a distinct positively charged surface patch, suggested to be involved in membrane association.

Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles.

Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there are still challenges to use this formulation for mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and a PEG-lipid.

Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens.

Ribonucleotide reductase (RNR) catalyses the only known de novo pathway for the production of all four deoxyribonucleotides that are required for DNA synthesis. It is essential for all organisms that use DNA as their genetic material and is a current drug target. Since the discovery that iron is required for function in the aerobic, class I RNR found in all eukaryotes and many bacteria, a dinuclear metal site has been viewed as necessary to generate and stabilize the catalytic radical that is essential for RNR activity.

Structure and Cooperativity of the Cytosolic Domain of the CorA Mg Channel from Escherichia coli.

Structures of the Mg bound (closed) and apo (open) states of CorA suggests that channel gating is accomplished by rigid-body motions between symmetric and asymmetric assemblies of the cytosolic portions of the five subunits in response to ligand (Mg) binding/unbinding at interfacial sites. Here, we structurally and biochemically characterize the isolated cytosolic domain from Escherichia coli CorA. The data reveal an Mg-ligand binding site located in a novel position between each of the five subunits and two Mg ions trapped inside the pore.

Synchrotron-based Nickel Mössbauer Spectroscopy.

We used a novel experimental setup to conduct the first synchrotron-based (61)Ni Mössbauer spectroscopy measurements in the energy domain on Ni coordination complexes and metalloproteins. A representative set of samples was chosen to demonstrate the potential of this approach. (61)NiCr2O4 was examined as a case with strong Zeeman splittings.

The solution configurations of inactive and activated DntR have implications for the sliding dimer mechanism of LysR transcription factors.

LysR Type Transcriptional Regulators (LTTRs) regulate basic metabolic pathways or virulence gene expression in prokaryotes. Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo- configuration that represses transcription to an active, expanded holo- form that promotes it. However, no LTTR has yet been observed to adopt both configurations.

Radar-enabled recovery of the Sutter's Mill meteorite, a carbonaceous chondrite regolith breccia.

Doppler weather radar imaging enabled the rapid recovery of the Sutter's Mill meteorite after a rare 4-kiloton of TNT-equivalent asteroid impact over the foothills of the Sierra Nevada in northern California. The recovered meteorites survived a record high-speed entry of 28.6 kilometers per second from an orbit close to that of Jupiter-family comets (Tisserand's parameter = 2.

Sound velocities of compressed Fe3C from simultaneous synchrotron X-ray diffraction and nuclear resonant scattering measurements.

The applications of nuclear resonant scattering in laser-heated diamond anvil cells have provided an important probe for the magnetic and vibrational properties of (57)Fe-bearing materials under high pressure and high temperature. Synchrotron X-ray diffraction is one of the most powerful tools for studying phase stability and equation of state over a wide range of pressure and temperature conditions. Recently an experimental capability has been developed for simultaneous nuclear resonant scattering and X-ray diffraction measurements using synchrotron radiation.

Electronic and magnetic structures of the postperovskite-type Fe2O3 and implications for planetary magnetic records and deep interiors.

Recent studies have shown that high pressure (P) induces the metallization of the Fe(2+)-O bonding, the destruction of magnetic ordering in Fe, and the high-spin (HS) to low-spin (LS) transition of Fe in silicate and oxide phases at the deep planetary interiors. Hematite (Fe(2)O(3)) is an important magnetic carrier mineral for deciphering planetary magnetism and a proxy for Fe in the planetary interiors. Here, we present synchrotron Mössbauer spectroscopy and X-ray diffraction combined with ab initio calculations for Fe(2)O(3) revealing the destruction of magnetic ordering at the hematite --> Rh(2)O(3)-II type (RhII) transition at 70 GPa and 300 K, and then the revival of magnetic ordering at the RhII --> postperovskite (PPv) transition after laser heating at 73 GPa.

Phonon density of states of metallic Sn at high pressure.

Determination of the lattice dynamics of Sn at high pressure has represented a major experimental challenge and eluded previous attempts. Here we report the first successful measurement of the phonon density of states of Sn at high pressure to 64 GPa using nuclear resonant inelastic x-ray scattering. We also present density functional theory calculations that are in excellent agreement with the measured data.