Bakerhanson1506

The analytic sample included 21 069 participants with a mean 9.8±3.8 years of follow-up. The Mediterranean diet score showed a trend toward an inverse association with risk of SCD after multivariable adjustment (hazard ratio [HR] comparing highest with lowest group, 0.74; 95% CI, 0.55-1.01; Ptrend=0.07). There was a trend toward a positive association of the Southern dietary pattern with risk of SCD (HR comparing highest with lowest quartile of adherence, 1.46; 95% CI, 1.02-2.10; Ptrend=0.06). Conclusions In REGARDS participants, we identified trends toward an inverse association of the Mediterranean diet score and a positive association of adherence to the Southern dietary pattern with risk of SCD.| Several diseases exhibit a high degree of heterogeneity and diverse reprogramming of cellular pathways. To address this complexity, additional strategies and technologies must be developed to define their scope and variability with the goal of improving current treatments. Nanomedicines derived from viruses are modular systems that can be easily adapted for combinatorial approaches, including imaging, biomarker targeting, and intracellular delivery of therapeutics. Here, we describe a "designer nanoparticle" system that can be rapidly engineered in a tunable and defined manner. Phage-like particles (PLPs) derived from bacteriophage lambda possess physiochemical properties compatible with pharmaceutical standards, and in vitro particle tracking and cell targeting are accomplished by simultaneous display of fluorescein-5-maleimide (F5M) and trastuzumab (Trz), respectively (Trz-PLPs). Trz-PLPs bind to the oncogenically active human epidermal growth factor receptor 2 (HER2) and are internalized by breast cancer cells of the HER2 overexpression subtype, but not by those lacking the HER2 amplification. Compared to treatment with Trz, robust internalization of Trz-PLPs results in higher intracellular concentrations of Trz, prolonged inhibition of cell growth, and modulated regulation of cellular programs associated with HER2 signaling, proliferation, metabolism, and protein synthesis. Given the implications to cancer pathogenesis and that dysregulated signaling and metabolism can lead to drug resistance and cancer cell survival, the present study identifies metabolic and proteomic liabilities that could be exploited by the PLP platform to enhance therapeutic efficacy. The lambda PLP system is robust and rapidly modifiable, which offers a platform that can be easily "tuned" for broad utility and tailored functionality.The hydration effect on the folding behavior of oligopeptides is of vital importance both in the structure basis of biomolecules and in the rational design of peptide-based materials, which however has rarely been addressed. Here we present the hydration impact on the spontaneous folding of dipeptides conjugated by the ferrocene spacer. In organic phase, the ferrocene-glycine-phenylalanine dipeptide formed a parallel β-sheet structure and Herrick's conformation, which underwent conformational transformation encountering aqueous media, by significantly switching dipeptide arm angles around the ferrocene axis up to 72°. The conformational transformation behavior aroused inversion of the chiroptical activity. Solid X-ray structures, proton nuclear magnetic resonance, chiroptical spectroscopy, and the density functional theory calculation were employed to unveil the hydration effect in the secondary structure transition, in which the rearrangement of hydrogen bonds played the vital role. This work deepens the understanding of water functioning in the structure modulation of biomolecules and also provides an alternative protocol in designing novel chiroptical switches and adaptive peptide-based biomaterials.For many types of vertical excitation energies, linear-response time-dependent density functional theory (LR-TDDFT) offers a useful degree of accuracy combined with unrivaled computational efficiency, although charge-transfer excitation energies are often systematically and dramatically underestimated, especially for large systems and those that contain explicit solvent. As a result, low-energy electronic spectra of solution-phase chromophores often contain tens to hundreds of spurious charge-transfer states, making LR-TDDFT needlessly expensive in bulk solution. Intensity borrowing by these spurious states can affect intensities of the valence excitations, altering electronic bandshapes. At higher excitation energies, it is difficult to distinguish spurious charge-transfer states from genuine charge-transfer-to-solvent (CTTS) excitations. In this work, we introduce an automated diabatization that enables fast and effective screening of the CTTS acceptor space in bulk solution. Our procedure introduces "natural charge-transfer orbitals" that provide a means to isolate orbitals that are most likely to participate in a CTTS excitation. GSK583 ic50 Projection of these orbitals onto solvent-centered virtual orbitals provides a criterion for defining the most important solvent molecules in a given excitation and be used as an automated subspace selection algorithm for projection-based embedding of a high-level description of the CTTS state in a lower-level description of its environment. We apply this method to an ab initio molecular dynamics trajectory of I-(aq) and report the lowest-energy CTTS band in the absorption spectrum. Our results are in excellent agreement with the experiment, and only one-third of the water molecules in the I-(H2O)96 simulation cell need to be described with LR-TDDFT to obtain excitation energies that are converged to less then 0.1 eV. The tools introduced herein will improve the accuracy, efficiency, and usability of LR-TDDFT in solution-phase environments.The efficient couplings of diverse N-arylureas and gem-difluoromethylene alkynes have been realized via Rh(III)-catalyzed chemoselective C-H alkenylation and [5 + 1] annulation, which were induced by the distinctive fluorine effect to provide the different coordination mode of the Rh(III) catalyst binding to the directing group, thereby giving the direct access to difluorinated 2-alkenyl arylureas and 3,4-dihydroquinazolin-2(1H)-ones bearing both an α-quaternary carbon center and a monofluoroalkenyl moiety with broad substrate compatibility and good functional group tolerance. The synthetic application in C-H alkenylation of the N-pyridylaniline, the late-stage [3 + 2] annulation, and the derivation of the obtained products has been also demonstrated to further strengthen the synthetic utility of the chemodivergent transformations.Unloading stress enhances oxidative stress, which in turn induces disuse muscle atrophy. This study evaluated the suppressive effect of lemon peel extract containing eriocitrin on muscle atrophy. Both lemon peel extract and eriocitrin suppressed weight loss in the gastrocnemius muscle under denervation in C57BL/6 mice. The mRNA level of ubiquitin ligases and their transcription factor were downregulated by eriocitrin. Eriocitrin inhibited the increase in lipid peroxidation and the ratio of glutathione disulfide/glutathione. These data suggest that eriocitrin ameliorated disuse muscle atrophy by suppressing the expression of ubiquitin ligase genes by its antioxidative effect.Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable in vivo, limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.Stretchable electronics have been spotlighted as promising next-generation electronics. In order to drive a specific unit device in an integrated stretchable device, the interconnection of the device should be placed in a desired position and addressed individually. In addition, practical stretchable interconnection requires reliable stretchability, high conductivity, optical transparency, high resolution, and fast and large-scale production. This study proposes an approach to meet these requirements. We print the single wavy polymer nanofibers (NFs) in a desired position and convert them into metal NF interconnections. The nanoscale diameter and the wavy cylindrical shape of the metal NFs are the main reasons for the reliable stretchability and the excellent transparency. Using the stretchable metal NFs and the stretchable organic semiconductor NFs, an array of all-stretchable transparent NF-field effect transistors (NF-FETs) is demonstrated. The highly integrated NF-FET array (10 FETs/mm2) shows uniform performance and good stability under repeated severe mechanical deformations.A major challenge to advance lipid nanoparticles (LNPs) for RNA therapeutics is the development of formulations that can be produced reliably across the various scales of drug development. Microfluidics can generate LNPs with precisely defined properties, but have been limited by challenges in scaling throughput. To address this challenge, we present a scalable, parallelized microfluidic device (PMD) that incorporates an array of 128 mixing channels that operate simultaneously. The PMD achieves a >100× production rate compared to single microfluidic channels, without sacrificing desirable LNP physical properties and potency typical of microfluidic-generated LNPs. In mice, we show superior delivery of LNPs encapsulating either Factor VII siRNA or luciferase-encoding mRNA generated using a PMD compared to conventional mixing, with a 4-fold increase in hepatic gene silencing and 5-fold increase in luciferase expression, respectively. These results suggest that this PMD can generate scalable and reproducible LNP formulations needed for emerging clinical applications, including RNA therapeutics and vaccines.Inspired by the Stenocara beetle's hydrophobic-hydrophilic surface, we fabricated hexagonally patterned hydrophobic-hydrophilic surfaces consisting of silicon and gold regions using colloidal lithography and selective surface functionalization. We investigated surface wettability for different patterns (hexagonally ordered nanotriangles and nanoholes) and the influence of surface functionalization (octadecanethiol and 16-mercaptohexadecanoic acid/octadecyltrichlorosilane (MHA/OTS)). The as-prepared patterned substrates exhibit hydrophilicity, which transforms to hydrophobicity after surface functionalization. The MHA/OTS functionalization results in maximum enhancement in the contact angle (114 ± 0.4°) with the least contact angle hysteresis (19 ± 2°). Fog harvesting studies show that the patterned substrate has a higher water collection rate, a factor of 1.32, than the nonpatterned substrates. A further enhancement in water collection (almost twice) is observed with selective functionalization. The patterned (nanohole) and functionalized (MHA/OTS) substrate facilitates rapid falling of droplets at a frequency of 20 mHz and an average droplet mass of 15 ± 2 mg/cm2.