Solid-state nuclear magnetic resonance under magic angle spinning (MAS) enhanced with dynamic nuclear polarization (DNP) is a powerful approach to characterize many important classes of materials, allowing access to previously inaccessible structural and dynamic parameters. Here, we present the first DNP MAS experiments using a 0.7 mm MAS probe, which allows us to reach spinning frequencies of 65 kHz, with microwave irradiation, at 100 K. At the highest magnetic field available for DNP today (21.1 T), we find that the polarizing agent HyTEK2 provides DNP enhancements as high as 200 at a spinning rate of 65 kHz at 100 K, and BDPA yields an enhancement of 106 under the same conditions. Fast spinning rates enable excellent DNP performance, but they also yield unprecedented 1H resolution under DNP conditions. We report well-resolved 1H-detected 1H-13C and 1H-15N correlation spectra of microcrystalline histidine·HCl·H2O.The growth of surface plasmonic microbubbles in binary water/ethanol solutions is experimentally studied. The microbubbles are generated by illuminating a gold nanoparticle array with a continuous wave laser. Plasmonic bubbles exhibit ethanol concentration-dependent behaviors. For low ethanol concentrations (fe) of ≲67.5%, bubbles do not exist at the solid-liquid interface. For high fe values of ≳80%, the bubbles behave as in pure ethanol. Only in an intermediate window of 67.5% ≲ fe ≲ 80% do we find sessile plasmonic bubbles with a highly nontrivial temporal evolution, in which as a function of time three phases can be discerned. (1) In the first phase, the microbubbles grow, while wiggling. (2) As soon as the wiggling stops, the microbubbles enter the second phase in which they suddenly shrink, followed by (3) a steady reentrant growth phase. Our experiments reveal that the sudden shrinkage of the microbubbles in the second regime is caused by a depinning event of the three-phase contact line. We systematically vary the ethanol concentration, laser power, and laser spot size to unravel water recondensation as the underlying mechanism of the sudden bubble shrinkage in phase 2.Lead-free double perovskites (DPs) with excellent moisture, light, and heat stability have been explored as alternatives to toxic lead halide perovskite (APbX3) (A for monovalent cation and X for Cl, Br, or I). However, the bandgaps of the current DPs are generally larger and either indirect or direct forbidden, which leads to weak visible light absorption and limitation for photovoltaic and other optoelectronic applications. Herein, we demonstrate the first synthesis of Cu2+-doped Cs2AgInCl6 double perovskite nanocrystals via a facile hot-injection solution approach. The electronic bandgap can be dramatically tuned from ∼3.60 eV (Cs2AgInCl6, parent) to ∼2.19 eV (Cu2+-doped Cs2AgInCl6) by varying the Cu2+ doping amount. We conclude that the decrease of bandgap is attributed to the overlap of the Ag-d/In-p/Cl-p orbitals and the Cu-3d orbitals in the valence band. The wide tunability of the optical and electronic properties makes Cu2+-Doped Cs2AgInCl6 DP NCs promising candidates for future optoelectronic device applications.Self-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR) ligands are ideal adjuvants for covalent linking to peptides or proteins. We here introduce a conjugation-ready TLR4 ligand, CRX-527, a potent powerful lipid A analogue, in the generation of novel conjugate-vaccine modalities. Effective chemistry has been developed for the synthesis of the conjugation-ready ligand as well as the connection of it to the peptide antigen. Different linker systems and connection modes to a model peptide were explored, and in vitro evaluation of the conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components.  https://www.selleckchem.com/products/kpt-8602.html  Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8+ T-cell-mediated killing of antigen-loaded target cells in vivo. Synthetic TLR4 ligands thus show great promise in potentiating the conjugate vaccine platform for application in cancer vaccination.N-acetyl-d-neuraminic acid (NeuAc) has attracted considerable attention because of its wide-ranging applications. The use of cheap carbon sources such as glucose without the addition of any precursor in microbial NeuAc production has many advantages. In this study, improved NeuAc production was attained through the optimization of amino sugar metabolism pathway kinetics and reservation of a phosphoenolpyruvate (PEP) pool in Escherichia coli. N-acylglucosamine 2-epimerase and N-acetylneuraminate synthase from different sources and their best combinations were used to obtain optimized enzyme kinetics and expression intensity, which resulted in a significant increase in NeuAc production. Next, after a design was engineered for enabling the PEP metabolic pathway to retain the PEP pool, the production of NeuAc reached 16.7 g/L, which is the highest NeuAc production rate that has been reported from using glucose as the sole carbon source.The growth of uterine fibroids is sex hormone-dependent and commonly associated with highly incapacitating symptoms. Most treatment options consist of the control of these hormonal effects, ultimately blocking proliferative estrogen signaling (i.e., oral contraceptives/antagonization of human gonadotropin-releasing hormone receptor [hGnRH-R] activity). Full hGnRH-R blockade, however, results in menopausal symptoms and affects bone mineralization, thus limiting treatment duration or demanding estrogen add-back approaches. To overcome such issues, we aimed to identify novel, small-molecule hGnRH-R antagonists. This led to the discovery of compound BAY 1214784, an orally available, potent, and selective hGnRH-R antagonist. Altering the geminal dimethylindoline core of the initial hit compound to a spiroindoline system significantly improved GnRH-R antagonist potencies across several species, mandatory for a successful compound optimization in vivo. In a first-in-human study in postmenopausal women, once daily treatment with BAY 1214784 effectively lowered plasma luteinizing hormone levels by up to 49%, at the same time being associated with low pharmacokinetic variability and good tolerability.