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Ultrafast ultrasound imaging based on plane waves (PWs) has attracted increasing attention owing to its high frame rate. However, the image quality provided by this technology, particularly in image contrast, does not meet clinical standards. Although the compounding method solves the issue of image quality degradation, it compromises the advantage of the high frame rate. Deep-learning-based methods have emerged as a promising avenue for improving the image quality of ultrasound imaging. However, their heavy reliance on high-quality training data poses challenges in practical implementation. Considering the imaging characteristic of B-mode images, in this article, we propose a self-supervised content-consistent contrast enhancement framework to enhance the contrast of B-mode ultrasound PW images. The proposed method consists of a content-preserving module to reconstruct a single image while preserving pixel information by maximizing the mutual information between the pixels of the reconstructed image and the input image, and a contrast-enhancing module to improve the contrast of the reconstructed image using the enhanced lower DR version of the input image by aligning their local perceptual information under multiple receptive fields. Experimental results demonstrate that our method yields improved image quality in terms of contrast ratio (CR), contrast-to-noise ratio (CNR), and generalized CNR (gCNR), when compared with the compounding method and other learning-based reconstruction methods that necessitate high-quality image training. Notably, the assessment conducted on the PICMUS dataset shows the commendable generalization capabilities of the proposed method. The code of our implementation is available at https://github.com/ Wang-aohua/SC3E.

Permeation enhancers (PEs), such as N-[8-(2-hydroxybenzoyl)amino]-caprylate (SNAC), have been reported to improve the oral absorption of various macromolecules. However, the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes, pH and other gastrointestinal barriers. In this study, we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration (insulin ≥ 40 μg/mL)-, ratio (SNAC/insulin ≥ 20:1)- and pH (≥ 6.8)-dependent manner, thus contributing to a significantly high efficacy of oral insulin delivery. Specifically, absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol. Furthermore, the complexes accelerated the exocytosis of insulin to the basolateral side, thereby enhancing its intestinal mucosal permeability. Eudragit® S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient (Papp) that was 6.6-fold higher than that of the insulin solution. In diabetic rats, hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into enteric-coated capsules. Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states, indicating a negligible food effect. Collectively, this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance.

Oral delivery of peptide/protein drugs has attracted worldwide attention due to its good patient compliance and convenience of administration. Orally administered nanocarriers always encounter the rigorous defenses of the gastrointestinal tract, which mainly consist of mucus and epithelium barriers. However, diametrically opposite surface properties of nanocarriers are required for good mucus penetration and high epithelial uptake. Here, bovine serum albumin (BSA) is adsorbed to cationic liposomes (CLs) to form protein corona liposomes (PcCLs). The aim of using PcCLs is to conquer the mucus and epithelium barriers, eventually improving the oral bioavailability of insulin. Investigations using in vitro and in vivo experiments show that the uptake amounts and transepithelial permeability of PcCLs are 3.24‐ and 7.91‐fold higher than that of free insulin, respectively. Further study of the behavior of PcCLs implies that BSA corona can be shed from PcCLs as they cross the mucus layer, which results in the exposure of CLs to improve the transepithelial transport. Intrajejunal administration of PcCLs in type I diabetic rats produces a remarkable hypoglycemic effect and increases the oral bioavailability up to 11.9%. All of these results imply that PcCLs may provide a new insight into the method for oral insulin delivery by overcoming the multiple barriers. Protein coronaare composed of cationic liposomes (CLs) as the nanocore and bovine serum albumin (BSA) as the protein corona. The PcCLs exhibit faster mucus penetration due to the neutral charge, and improve the cellular internalization as the exposed CLs after BSA degradation in the mucus layer, thus these PcCLs can enhance the oral bioavailability of insulin.