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To establish a breast lesion risk stratification system using ultrasound images to predict breast malignancy and assess Breast Imaging Reporting and Data System (BI-RADS) categories simultaneously.This multicenter study prospectively collected a dataset of ultrasound images for 5012 patients at thirty-two hospitals from December 2018 to December 2020. A deep learning (DL) model was developed to conduct binary categorization (benign and malignant) and BI-RADS categories (2, 3, 4a, 4b, 4c, and 5) simultaneously. The training set of 4212 patients and the internal test set of 416 patients were from thirty hospitals. The remaining two hospitals with 384 patients were used as an external test set. Three experienced radiologists performed a reader study on 324 patients randomly selected from the test sets. We compared the performance of the DL model with that of three radiologists and the consensus of the three radiologists.In the external test set, the DL model achieved areas under the receiver operating characteristic curve (AUCs) of 0.980 and 0.945 for the binary categorization and six-way categorizations, respectively. In the reader study set, the DL BI-RADS categories achieved a similar AUC (0.901 vs. 0.933, p = 0.0632), sensitivity (90.98% vs. 95.90%, p = 0.1094), and accuracy (83.33% vs. 79.01%, p = 0.0541), but higher specificity (78.71% vs. 68.81%, p = 0.0012) than those of the consensus of the three radiologists.The DL model performed well in distinguishing benign from malignant breast lesions and yielded outcomes similar to experienced radiologists. This indicates the potential applicability of the DL model in clinical diagnosis.• The DL model can achieve binary categorization for benign and malignant breast lesions and six-way BI-RADS categorizations for categories 2, 3, 4a, 4b, 4c, and 5, simultaneously. • The DL model showed acceptable agreement with radiologists for the classification of breast lesions. • The DL model performed well in distinguishing benign from malignant breast lesions and had promise in helping reduce unnecessary biopsies of BI-RADS 4a lesions.

Simple Summary For the first time, this study investigated the extraction of bioactive substances with different polarities from immature honey pomelo fruit (IPF), a by-product of pomelo planting processing that causes resource waste and environmental pollution, using novel continuous phase transition extraction technology (CPTE). The results showed that CPTE was suitable for extracting essential oil, naringin, and pectin in sequence according to their polarities. The naringin extraction process was optimized by the response surface methodology, resulting in an extract ratio up to 99.47%. Moreover, the pectin extracted from IPF by CPTE showed better quality compared to commercial counterparts, as evidenced by lower protein and ash contents and higher white value. Together, these results suggested that CPTE could be a promising technology to improve the application value of IPF. For instance, the extracted bioactive components can be utilized as nutraceutical food ingredients. The scientific insights from this study will contribute to the development of functional food ingredients and comprehensive utilization of farming by-products. Abstract The immature honey pomelo fruit (IPF) is a huge agro-industrial by-product generated during pomelo planting. Although IPF is rich in nutrients, more than 95% of IPF is discarded annually, which causes resource waste and a serious environmental problem. Here, we report a novel continuous phase transition extraction technology (CPTE) to improve the comprehensive utilization of IPF by sequentially generating high value products and solve pollution problems related to their disposal. First, essential oil was successively extracted by CPTE at a yield of 1.12 ± 0.36%, in which 43 species were identified. Second, naringin extraction parameters were optimized using the response surface methodology (RSM), resulting in a maximum extraction rate of 99.47 ± 0.15%. Finally, pectin was extracted at a yield of 20.23 ± 0.66%, which is similar to the contents of commercial pectin. In conclusion, this study suggested that IPF was an excellent potential substrate for the production of value-added components by CPTE.

A mixture of ceramide (CER) and lecithin (LEC) at specific ratios was capable of forming oleogels in sunflower oil triggered by adding a trace amount of water. It was noted that the addition of water at different temperatures (TW) resulted in different gelation behaviors and microstructures. To better illuminate the assembly mechanism at different TW, samples with water added at different TW (20 °C, 45 °C, 70 °C and 95 °C) were prepared. The viscoelastic properties, microstructures, and the crystal packing of these samples were investigated. It was observed that all samples prepared at TW of 20 °C and 95 °C formed gels, while most samples prepared at TW of 45 °C and 70 °C were too weak to form gels. Gels prepared at 95 °C were stronger but more fragile in texture compared to gels produced at 20 °C. The crystal morphology of gels drastically changed with TW. Spindle-shaped crystals were observed in gels prepared at low TW (20 °C), while gels prepared at high TW (95 °C) exhibited a network with packed oil droplets stabilized by lamellar shells together with fibrillar crystals in the bulk phase. X-ray diffractograms showed a different reflection peak (d-spacing of 14.5 Å) in gel prepared at 20 °C, compared to the d-spacing in oleogels with a single gelator (13.14 Å and 15.33 Å, respectively, for CER and LEC). Gel prepared at 95 °C showed two long-spacing characteristic peaks, which correspond to the characteristic peaks of CER gel (∼13 Å) and LEC gel (∼12 Å). Fourier transform infrared spectroscopy results indicated that the different gelation behaviors at different TW were mainly caused by vibrational changes in the amide bond of CER. Our hypothesized assembly mechanism can be concluded as: increasing TW resulted in the conversion of CER and LEC crystallization from co-assembly (TW = 20 °C) to self-sorting by individual gelators (TW = 95 °C). In this study, novel water-induced oleogels were produced by manipulating TW, and such information further assists the rational design of lipid-based healthy fat products.

Ceramide (CER) is a novel food-grade organogelator with beneficial health effects. Lecithin (LEC) is not an effective gelator; however, it may alter the crystal morphology of the host gelator in a multicomponent system. In this paper, LEC and CER were mixed at various molar ratios in sunflower oil leading to different gelation behaviors. It was interesting since in this multicomponent system, gels formed when there was more less-effective gelator (LEC), while gels hardly formed when there was more effective gelator (CER). This drew our attention since there might not be only one kind of assembly mode between the LEC and the CER. A comprehensive rheological investigation was conducted. It was found that at specific ratios (6L4C and 5L5C), strong gels (G' > 1.0 × 105 Pa) formed with superior oil binding capacity (up to 99.84%). Meanwhile, these gels exhibited higher tolerance level to permanent deformation than the monocomponent gel. However, weak gels were observed off the optimal ratio (8L2C, 7L3C, 4L6C and 3L7C). The crystal morphology of gels drastically changed with change in gelator proportion. Short needle-like crystals and small rosette crystals were observed in 6L4C and 5L5C, respectively, while other samples exhibited spherulite-shaped crystals (8L2C, 7L3C, 4L6C, and 3L7C), which differed from any of the monocomponent gel structures (10L0C and 0L10C). Results from differential scanning calorimetry and polarized light microscopy suggested that the macroscopic properties are determined by the morphology and distribution of crystals rather than the crystallinity of the matrix. Fourier transform infrared spectroscopy results indicated the presence of van der Waals forces and the formation of hydrogen bonding between the phosphate of the LEC and the amide group of the CER. The above results indicated that the LEC and CER co-assembled at approximately equal molar ratio, and the redundant LEC or CER at other ratios self-sorted to combine with the co-assembled fibers by lateral association, leading to potentially different underlying microstructures. These multicomponent supramolecular oleogels with high tunability may further broaden their applicability in various healthy lipid-based product formats.

Ceramide (CER) is a highly effective organogelator with numerous health implications. Lecithin (LEC) is often used as a crystal modifier to improve gel properties. It was found in this study that in the presence of a small amount of water, CER and LEC self-assembled at specific ratios and form oleogels in sunflower oil (SFO), and the structure of which differed from any of the mono-component gel structures. To the best of our knowledge, this is the first water-induced multi-component oleogelation reported to date. To clarify when gelation occurs, a phase diagram of the four-component system SFO/CER/LEC/water was established and characterized. In the gel region, confocal laser scanning microscopy revealed that water was evenly distributed in the self-assembled microstructure. To clarify the vital role of water in formation of stable gel, a series of samples with varying ratios in CER and LEC with and without water were explored. The thermal properties, viscoelastic properties, microstructures, as well as crystal packing were investigated. With water added, the microscopic structures of CER/LEC gels changed from three-dimensional dendritic crystals to two-dimensional rod-like or platelet-like crystals, which are more effective at structuring liquid oil. A different reflection was observed (d-spacing of 14.9 Å), suggesting the rearrangement in crystal packing of ceramide and lecithin molecules, compared to the d-spacing in oleogels with single gelator (13.1 Å and 15.3 Å, respectively for ceramide and lecithin). Fourier transform infrared spectroscopy results indicated the presence of interaction between water and gelators, which confirmed the importance of water in self-assembly of this mixed-gelator system. Water-induced conversion of oleogelation provides alternatives in producing hard-stock fat replacers as well as possibilities to incorporate water-soluble nutrients into oil-based products.

Peptides are a promising class of gelators, due to their structural simplicity, biocompatibility and versatility. Peptides were synthesized based on four amino acids: leucine, phenylalanine, tyrosine and tryptophan. These peptide gelators, with systematic structural variances in side chain structure and chain length, were investigated using Hansen solubility parameters to clarify molecular features that promote gelation in a wide array of solvents. It is of utmost importance to combine both changes to structural motifs and solvent in simultaneous studies to obtain a global perspective of molecular gelation. It was found that cyclization of symmetric dipeptides, into 2,5-diketopiperazines, drastically altered the gelation ability of the dipeptides. C-L-LL and C-L-YY, which are among the smallest peptide LMOGs reported to date, are robust gelators with a large radius of gelation (13.44 MPa1/2 and 13.90 MPa1/2, respectively), and even outperformed L-FF (5.61 MPa1/2). Interestingly, both linear dipeptides (L-FF and L-LL) gelled similar solvents, yet when cyclized only cyclo-dityrosine was a robust gelator, while cyclo-diphenylalanine was not. Changes in the side chains drastically affected the crystal morphology of the resultant gels. Symmetric cyclo dipeptides of leucine and tyrosine were capable of forming extremely high aspect ratio fibers in numerous solvents, which represent new molecular motifs capable of driving self-assembly.

Previous studies showed that inflammation and apoptosis were involved in the pathogenesis of hypoxic-ischemic brain injury. The immature brain is particularly vulnerable to damage. Intracerebral injection of glial cell line-derived neurotrophic factor (GDNF) has been shown to reduce the injury induced by hypoxia-ischemia (HI). In this study, the neuroprotective effect of intracerebral ultrasound-induced dissolution of lipid-coated GDNF microbubbles was investigated in a neonatal rat model of hypoxic-ischemic brain injury. Hypoxic-ischemic injury was induced in 7-day-old rats in the present study. The rats with hypoxia-ischemia received intracerebral injections of GDNF-containing microbubbles (0.5 mg/kg). They then received low frequency ultrasound stimulation (20 kHz, 2 h intervals for a total of 24 h and each time lasted for 1 min) to induce release of GDNF into the right striatum. We found that low frequency ultrasound stimulation can induce lipid-coated GDNF microbubbles to release GDNF. Ultrasound-induced dissolution of lipid-coated GDNF microbubbles treatment reduced infarction volume and improved neurological outcomes in neonatal rats. In the meanwhile, the microbubbles attenuated the production of inducible nitric oxide synthase, nitric oxide and tumor necrosis factor-alpha, as well as the activation of caspase-3 in insulted side of brain in neonatal rats. These data demonstrated that ultrasound-induced dissolution of lipid-coated GDNF microbubbles treatment can provide a neuroprotective effect against hypoxia-ischemia in neonatal rats.