Phillipsgaarde5421

We envision that the approach described herein will find useful applications in chemical biology, medical diagnostics, and biosensing.3D culture platforms with tunable stiffness have the potential to improve many applications, such as drug discovery, organoid studies, and stem cell differentiation. Both dimensionality and stiffness regulate crucial and relevant cellular processes. However, 3D culture models are often limited in throughput and difficult to adopt for widespread use. Here, we demonstrate an accessible 3D, stiffness-tunable tissue culture platform, based on an interpenetrating network of collagen-1 and alginate. When blended with polymers that induce phase separation, these networks can be bioprinted at microliter volumes, using standard liquid handling infrastructure. We demonstrate robust reproducibility in printing these microgels, consistent tunability of mechanical properties, and maintained viability of multiple printed cell types. To highlight the utility and importance of this system, we demonstrate distinct morphological changes to cells in culture, use the system to probe the role of matrix mechanics and soluble factors in a collagen contraction assay, and perform a prototype viability screen against a candidate chemotherapeutic, demonstrating stiffness-dependent responses.For site-specific diseases such as atherosclerosis, it is desirable to noninvasively and locally deliver therapeutics for extended periods of time. High-intensity focused ultrasound (HIFU) provides targeted drug delivery, yet remains unable to sustain delivery beyond the HIFU treatment time. Furthermore, methods to validate HIFU-enhanced drug delivery remain limited. In this study, we report on HIFU-targeted implantation of degradable drug-loaded sound-sensitive multicavity PLGA microparticles (mcPLGA MPs) as a theranostic agent for the treatment of arterial lesions. Once implanted into the targeted tissue, mcPLGA MPs eluted dexamethasone for several days, thereby reducing inflammatory markers linked to oxidized lipid uptake in a foam cell spheroid model. Furthermore, implanted mcPLGA MPs created hyperechoic regions on diagnostic ultrasound images, and thus noninvasively verified that the target region was treated with the theranostic agents. This novel and innovative multifunctional theranostic platform may serve as a promising candidate for noninvasive imaging and treatment for site-specific diseases such as atherosclerosis.Integration of novel bio-/nanostructures as effective sensing platforms is still of great significance for robust and rapid analysis. Herein, a novel metal-organic framework-derived NiCo2O4 was synthesized via a feasible templating method. Significantly, redox couples of both Ni3+/Ni2+ and Co3+/Co2+ provided richer oxidation-reduction reactions, thereby leading to an enhanced catalytic activity. Furthermore, NiCo2O4 as an enzyme mimic with peroxidase-like activity and oxidase-like activity could oxidize colorless thylbenzidine (TMB) to blue oxTMB in the absence of H2O2. Thus, a sensitive chromogenic sensing platform for detecting Fe2+, thiourea, cysteine (Cys), and epigallocatechin-3-gallate (EGCG) was proposed. The colorimetric detection methods exhibited great features of low limit of detection (LOD) and broad linear range. Owing to the complexation reaction, the chromogenic sensing system of TMB + NiCo2O4 + Cys achieved effective detection of Cu2+ and Mn2+ with the LODs of 0.0022 and 0.0181 mM, respectively. Developed detection methods with wide linear ranges of 0.008-0.1 mM for Cu2+ and 0.08-1 mM for Mn2+ had excellent practical potential. Similarly, the reaction system of TMB + NiCo2O4 + EGCG could achieve the colorimetric detection of Cu2+ and Fe3+. The great chromogenic sensing performance for detecting Cu2+ and Fe3+ with a broad linear range and a low LOD could be also realized.The constructure of a heterostructured interface is an effective way to design highly durable and efficient water oxidation electrocatalysts. Herein, Cu/CuCN with heterointerfaces is the first synthesized case through a simple epitaxial-like growth method, displaying superior activity and stability under pH-universal media. Associated with high electron transport and transfer of the epitaxial interfacial area, the Cu/CuCN pre-catalyst is applied to deliver the oxygen evolution reaction (OER) with lower overpotentials of 250 mV (forward scan) and 380 mV (backward scan) at 10 mA cm-2 and demonstrates better intrinsic activity (jECSA of 1.0 mA cm-2 at 420 mV) and impressive stability (136 h) in 1.0 M KOH, which exceeds most previous catalysts. Even using a nominal voltage of 1.5 V of a AA battery can drive the overall water-splitting setup. Experiments combined with theoretical simulations further uncover the existence of CuO species at the heterointerface during basic OER, which is evidence of better OER performance with abundant active sites that accelerate the conversion kinetics.ConspectusDirecting group (DG) assistance provides a good solution to the problems of reactivity and selectivity, two of the fundamental challenges in C(sp3)-H activation. However, the activation of unbiased methylene C(sp3)-H bonds remains challenging due to the high heterolytic bond dissociation energy and substantial steric hindrance. Two main strategies have been developed thus far, that is, use of a strongly coordinating bidentate DG pioneered by Daugulis and use of a weakly coordinating monodentate DG accelerated by pyridine-type ligands, as disclosed by Yu. The seminal work by Daugulis sparked significant interest in the application of the monoanionic bidentate auxiliary in aliphatic C-H activation reactions. Our research has focused on enabling the divergent functionalization and enantiotopic differentiation of unactivated methylene C-H bonds. Inspired by the structure of bidentate 8-aminoquinoline and the accelerating effect of the gem-dimethyl moiety in cyclometalations, we developed a strongly coorabled Pd(II)-catalyzed inter- and intramolecular arylation of unbiased methylene C(sp3)-H bonds with high enantioselectivity, whereas the latter promoted a series of asymmetric functionalization reactions, such as alkynylation, arylation, alkenylation/aza-Wacker cyclization, and intramolecular amidation. The unexpectedly high stereocontrol compared with other bidentate DGs might be attributable to steric communication between the ligand and gem-dimethyl moiety of PIP amine. Thus far, the combination of PIP amine DG with 3,3'-disubstituted BINOL ligands is arguably the most general strategy for asymmetric functionalization of unbiased methylene C(sp3)-H bonds. BMS-265246 Finally, the ease of installation and removal of PIP under mild conditions and synthetic applications are described.