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Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics, and offers stable delivery outcomes. However, many therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid–liquid phase separation that protects unstable proteins. A three‐layer microneedle for the controlled release of three different molecules is designed. Through micromolding, microneedles are efficiently generated, which benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The three layers, in the microneedles, release the cargo in a three‐phase manner. The released protein maintains its structure well. Moreover, layer thickness can be controlled by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics, thus promising uses in multi‐drug therapies through a single treatment.

 

Macromolecularly crowded coacervate is useful in protein delivery for tissue engineering and regenerative medicine. However, coacervate tends to aggregate easily, which impedes their application. Here, this work presents a method to prepare coacervate with enhanced stability. This work assembles phospholipids on the surface of a coacervate to form lipocoacervate (LipCo). The resultant LipCo possesses a discrete spherical structure with a coacervate interior and phospholipid outer shell. The size of LipCo does not change over the four‐week observation window, whereas coacervate coalesced into one bulk phase within 30 min. This work uses vascular endothelial growth factor‐C (VEGF‐C) and fibroblast growth factor‐2 (FGF‐2) as examples to test LipCo's ability to maintain protein bioactivity. The in vitro lymphangiogenesis assay demonstrates that human dermal lymphatic endothelial cells (LECs) formed increased network of cord in VEGF‐C and FGF‐2 loaded LipCo group compared to free proteins and proteins loaded in coacervate. Overall, LipCo could serve as a protein delivery vehicle with improved colloidal stability.

 

Abstract We image the shallow structure across the East Bench segment of the Wasatch fault system in Salt Lake City using ambient noise recorded by a month-long temporary linear seismic array of 32 stations. We first extract Rayleigh-wave signals between 0.4 and 1.1 s period using noise cross correlation. We then apply double beamforming to enhance coherent cross-correlation signals and at the same time measure frequency-dependent phase velocities across the array. For each location, based on available dispersion measurements, we perform an uncertainty-weighted least-squares inversion to obtain a 1D VS model from the surface to 400 m depth. We put all piece-wise continuous 1D models together to construct the final 2D VS model. The model reveals high velocities to the east of the Pleistocene Lake Bonneville shoreline reflecting thinner sediments and low velocities particularly in the top 200 m to the west corresponding to the Salt Lake basin sediments. In addition, there is an ∼400-m-wide low-velocity zone that narrows with depth adjacent to the surface trace of the East Bench fault, which we interpret as a fault-related damage zone. The damage zone is asymmetric, wider on the hanging wall (western) side and with greater velocity reduction. These results provide important constraints on normal-fault earthquake mechanics, Wasatch fault earthquake behavior, and urban seismic hazard in Salt Lake City. 

Abstract Ferroelectric topological objects provide a fertile ground for exploring emerging physical properties that could potentially be utilized in future nanoelectronic devices. Here, we demonstrate quasi-one-dimensional metallic high conduction channels associated with the topological cores of quadrant vortex domain and center domain (monopole-like) states confined in high quality BiFeO 3 nanoislands, abbreviated as the vortex core and the center core. We unveil via the phase-field simulation that the superfine metallic conduction channels along the center cores arise from the screening charge carriers confined at the core region, whereas the high conductance of vortex cores results from a field-induced twisted state. These conducting channels can be reversibly created and deleted by manipulating the two topological states via electric field, leading to an apparent electroresistance effect with an on/off ratio higher than 10 3 . These results open up the possibility of utilizing these functional one-dimensional topological objects in high-density nanoelectronic devices, e.g. nonvolatile memory.