Bankscastro0655

Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.Surface modification using alginic acid and its salt, alginate (Alg), has attracted much attention owing to its potential applications in various fields, including tissue engineering, drug delivery, antiplatelet surface preparation, and energy-storage technologies. In these applications, efficient immobilization of Alg on the solid surface is required because the delamination of the surface-bound Alg eventually leads to a significant decrease in its function. Therefore, much effort has been made to introduce Alg onto solid surfaces in a stable manner. Despite recent advances, existing methods for immobilizing Alg on surfaces have some limitations (i) derivatization of Alg is typically also required and (ii) these methods only function under specific reaction conditions. Herein, we report a Zr(IV)-mediated strategy to immobilize Alg on solid surfaces. We demonstrate efficient Alg grafting onto carboxyl-, catechol-, polydopamine-, and tannic acid-functionalized surfaces via Zr(IV)-mediated cross-linking reactions. This strategy yields Alg multilayers that suppress fibroblast and platelet adhesion onto the solid surfaces. Furthermore, we show that the Alg multilayers can be selectively constructed on specific sites of solid surfaces. Given its ease of use and the wide selection of available carboxyl polymers, the current strategy is expected to be a useful tool for preparing functional polymer films for various applications.Isotopic mixtures of p-H2 and o-D2 molecules have been an attractive binary system because they include two kinds of purely isotopic molecules which possess the same electronic potential but the twice different mass inducing differently pronounced nuclear quantum effects (NQEs). Accessing details of structures and dynamics in such quantum mixtures combining complex molecular dynamics with NQEs of different strengths remains a challenging problem. Taking advantage of the nonempirical molecular dynamics method which describes p-H2 and o-D2 molecules, we found that the liquid dynamics slows down at a specific mixing ratio, which can be connected to the observed anomalous slowdown of crystallization in the quantum mixtures. CDK activation We attributed the decelerated dynamics to the component-dependent supercooling of p-H2 taking place in the mixtures, demonstrating that there is an optimal mixing ratio to hinder crystallization. The obtained physical insights will help in experimentally controlling and achieving unknown quantum mixtures including superfluid.Neurodegenerative diseases are irreversible conditions that result in progressive degeneration and death of nerve cells. Although the underlying mechanisms may vary, oxidative stress is considered to be one of the major causes of neuronal loss. Importantly, there are still no comprehensive treatments to completely cure these diseases. Therefore, protecting neurons from oxidative damage may be the most effective therapeutic strategy. Here we report a neuroprotective effects of a novel hybrid compound (dlx-23), obtained by conjugating alpha-lipoic acid (ALA), a natural antioxidant agent, and 3-n-butylphthalide (NBP), a clinical anti-ischemic drug. Dlx-23 protected against neuronal death induced by both H2O2 induced oxidative stress in Cath.-a-differentiated (CAD), and 6-OHDA, a toxin model of Parkinson's disease (PD) in SHSY-5Y cells. These activities proved to be more potent than the parent compound (ALA) alone. Dlx-23 scavenged free radicals, increased glutathione levels, and prevented mitochondria damage. In addition, live imaging of primary cortical neurons demonstrated that dlx-23 protected against neuronal growth cones damage induced by H2O2. Taken together these results suggest that dlx-23 has substantial potential to be further developed into a novel neuroprotective agent against oxidative damage and toxin induced neurodegeneration.A scalable endo-selective synthesis of 2,3,4,5-tetrasubstituted pyrrolidines via cycloaddition of nitroalkenes and azome-thine ylides is reported using a P,N-type ferrocenyl ligand and [Cu(OTf)]2·C6H6. The robust method is tolerant of a wide range of functionalities, including rarely-reported quaternary nitroalkene substitution and heteroaromatic and hindered ortho-substituted arenes on the azomethine ylide. Subsequent transformations highlight the utility of the method in the synthesis of densely-functionalized small molecules suitable for fragment-based drug discovery and the cystic fibrosis C2-corrector clinical candidate ABBV-3221.A chiral molecule with octahedral symmetry, Re6C32, has been identified using first-principles calculations. It is a hollow cage with the shape of Catalan pentagonal icositetrahedron. The calculated vibrational frequencies are in the range of 83.0-1341.2 cm-1, which indicate the stability of the Re6C32 molecule. Molecular dynamics simulations show that the topological structure of the Re6C32 molecule is well maintained up to 1500 K. The electronic structural analysis shows that there are significant p-d orbital hybridizations near the Fermi level. Moreover, the Re6C32 molecule is magnetic with spin magnetic moment of 12 μB. This magnetic carbon-based hollow Re6C32 cage may become a candidate for single-molecule devices.