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Nanobubbles (NBs) generated-nanojets membrane poration have gained enormous attention. In this study, NBs were fabricated as a novel green approach to assist ionic liquid (IL) [C4C1im][BF4] extraction of polyphenols from Carya cathayensis Sarg. husk. NBs were successfully generated with mean size of 85.47 ± 5 nm, zeta potential of +39 ± 2.24 mV, and concentration of 21.15 ± 0.75 × 108 particles/mL (stable for over 48 h in IL solution). Compared to common solutions extract, IL-NBs extract showed significantly higher (p less then 0.05) antioxidant activity and polyphenols yields with a total polyphenol, total flavonoid, and total tannins contents of 85.67 ± 2.05 mg GAE/g DW, 42.44 ± 1.17 mg CE/g DW, and 8.2 ± 0.05 mg TAE/g DW, respectively. The SEM results confirmed that NBs' nanojets caused morphological destruction of the husk powder. Overall, IL-NBs solution showed better extraction efficiency of polyphenols than other solutions, giving insight into a new "green" nanotechnology-based extraction method.Recent studies have shown that mild to moderate iron chlorosis can have positive effects on grape quality potential, including volatile profile. The main objective of this work was to investigate, for the first time, how moderate iron stress in grapevines affects the presence of volatile organic compounds (VOCs) in wines. The study was carried out during 2018-2019 seasons, in 20 Tempranillo vineyard subzones with different degree of iron deficiency, located in Ribera del Duero (North-Central Spain). The results showed that moderate iron stress increased in wines the concentrations of VOCs associated with floral notes, such as 2-phenylacetaldehyde, 2-phenylethanol and 2-phenylethyl acetate, while reducing the presence of C6-alcohols, responsible for green-herbaceous aroma. A favourable reduction of pH and a betterment of parameters related to colour were detected in wines from iron deficient subzones. Chlorosis incidence was associated to improvements in wine sensory attributes as layer intensity, black fruit and aroma intensity.A colorimetric indicator cube for use in smart packaging was designed and fabricated to detect ethanol produced by microbial fermentation in preserved baby mangoes. The presence and level of ethanol was indicated by color variations of the indicator cube, which consists of porous melamine foam (MF) that entraps an indicator solution of potassium dichromate and sulfuric acid. Within the packaging, the cube sits behind a gas-permeable membrane. The morphological structure of MF was studied by digital microscope and X-ray fluorescence analysis. In the optimal condition, the indicator cube exhibited distinct color changes from yellow to brown, green and blue over an ethanol concentration range from 0.25% to 5.0%. Color changes were clearly visible to the naked eye. The repeatability of the ethanol indicator cube was good and storage stability was maintained for up to 19 and 74 days at room and refrigeration temperatures, respectively. The smart packaging was applied to detect ethanol in preserved baby mangoes at different storage times.A systematic review according to the PRISMA reporting standard was performed to identify causes of use errors in mechanical ventilators described in the literature. The PubMed search resulted in the inclusion of 16 papers. The errors described were systematically analyzed with regard to their causes and categorized in an adapted cause-and-effect diagram. The causes of use errors were related to specific usability issues and to the general condition that medical staff often work with different ventilators. When many devices are used, the different user interfaces are a source of use errors, since, for example, the same ventilation modes have different names. In order to avoid the identified causes for use errors in the future, this work offers manufacturers of ventilation devices design recommendations and the possibility to include the results in their risk management. In addition, standardizing user interface content across all ventilators, as in ISO 19223, can help reduce use errors.Multifunctional ligands as an essential variant of polypharmacology are promising candidates for the treatment of multi-factorial diseases like Alzheimer's disease. Based on clinical evidence and following the paradigm of multifunctional ligands we have rationally designed and synthesized a series of compounds targeting processes involved in the development of the disease. The biological evaluation led to the discovery of two compounds with favorable pharmacological characteristics and ADMET profile. Compounds 17 and 35 are 5-HT6R antagonists (Ki = 13 nM and Ki = 15 nM respectively) and cholinesterase inhibitors with distinct mechanisms of enzyme inhibition. Compound 17, a tacrine derivative is a reversible inhibitor of acetyl- and butyrylcholinesterase (IC50 = 8 nM and IC50 = 24 nM respectively), while compound 35 with rivastigmine-derived phenyl N-ethyl-N-methylcarbamate fragment is a selective, pseudo-irreversible inhibitor of butyrylcholinesterase (IC50 = 455 nM). Both compounds inhibit aggregation of amyloid β in vitro (75% for compound 17 and 68% for 35 at 10 μM) moreover, compound 35 is a potent tau aggregation inhibitor in cellulo (79%). In ADMET in vitro studies both compounds showed acceptable metabolic stability on mouse liver microsomes (28% and 60% for compound 17 and 35 respectively), no or little effect on CYP3A4 and 2D6 up to a concentration of 10 μM and lack of toxicity on HepG2 cell line (IC50 values of 80 and 21 μM, for 17 and 35 respectively). Based on the pharmacological characteristics and favorable pharmacokinetic properties, we propose compounds 17 and 35 as an excellent starting point for further optimization and in-depth biological studies.The widespread and repeated use of broad-spectrum bactericides has led to an increase in resistance. Developing novel broad-spectrum bactericides cannot solve the resistance problem, and may even aggravate it. The design of specific and selective bactericides has become urgent. A specific bactericidal design strategy was proposed by introducing exogenous metabolites in this study. This strategy was used to optimize two known antibacterial agents, luteolin (M) and Isoprothiolane (D), against Xoo. Based on the prodrug principles, target compound MB and DB were synthesized by combing M or D with exogenous metabolites, respectively. Bactericidal activity test results demonstrated that while the antibacterial ability of target compounds was significantly improved, their selectivity was also well enhanced by the introducing of exogenous metabolites. Comparing with the original compound, the antibacterial activity of target compound was significantly increased 92.0% and 74.5%, respectively. The optimized target compounds were more easily absorbed, and the drug application concentrations were much lower than those of the original agents, which would greatly reduce environmental pollution and relieve resistance risk. Our proposed strategy is of great significance for exploring the specific and selective bactericides against other pathogens.Human sirtuin 5 (SIRT5) plays pivotal roles in metabolic pathways and other biological processes, and is involved in several human diseases including cancer. Development of new potent and selective SIRT5 inhibitors is currently desirable to provide potential therapeutics for related diseases. Herein, we report a series of new 3-thioureidopropanoic acid derivatives, which were designed to mimic the binding features of SIRT5 glutaryl-lysine substrates. Structure-activity relationship studies revealed several compounds with low micromolar inhibitory activities to SIRT5. Computational and biochemical studies indicated that these compounds exhibited competitive SIRT5 inhibition with respect to the glutaryl-lysine substrate rather than nicotinamide adenine dinucleotide cofactor. Moreover, they showed high selectivity for SIRT5 over SIRT1-3 and 6 and could stabilize SIRT5 proteins as revealed by thermal shift analyses. This work provides an effective substrate-mimicking strategy for future inhibitor design, and offers new inhibitors to investigate their therapeutic potentials in SIRT5-associated disease models.The scaphoid is located in the carpals. Owing to the body structure and location of the scaphoid, scaphoid fractures are common and it is difficult to heal. Three-dimensional reconstruction of scaphoid fracture can accurately display the fracture surface and provide important support for the surgical plan involving screw placement. To achieve this goal, in this study, the cross-scale residual network (CSR-Net) is proposed for scaphoid fracture segmentation. In the CSR-Net, the features of different layers are used to achieve fusion through cross-scale residual connection, which realizes scale and channel conversions between the features of different layers. It can establish close connections between different scale features. The structures of the output layer and channel are designed to establish the CSR-Net as a multi-objective architecture, which can realize scaphoid fracture and hand bone segmentations synchronously. signaling pathway In this study, 65 computed tomography images of scaphoid fracture are tested. Quantitative metrics are used for assessment, and the results obtained show that the CSR-Net achieves higher performance in hand bone and scaphoid fracture segmentations. In the visually detailed display, the fracture surface is clearer and more intuitive than those obtained from other methods. Therefore, the CSR-Net can achieve accurate and rapid scaphoid fracture segmentation. Its multi-objective design provides not only an accurate digital model, but also a prerequisite for navigation in the hand bone.Histopathological images provide a gold standard for cancer recognition and diagnosis. Existing approaches for histopathological image classification are supervised learning methods that demand a large amount of labeled data to obtain satisfying performance, which have to face the challenge of limited data annotation due to prohibitive time cost. To circumvent this shortage, a promising strategy is to design semi-supervised learning methods. Recently, a novel semi-supervised approach called Learning by Association (LA) is proposed, which achieves promising performance in nature image classification. However, there are still great challenges in its application to histopathological image classification due to the wide inter-class similarity and intra-class heterogeneity in histopathological images. To address these issues, we propose a novel semi-supervised deep learning method called Semi-HIC for histopathological image classification. Particularly, we introduce a new semi-supervised loss function combining an association cycle consistency (ACC) loss and a maximal conditional association (MCA) loss, which can take advantage of a large number of unlabeled patches and address the problems of inter-class similarity and intra-class variation in histopathological images, and thereby remarkably improve classification performance for histopathological images. Besides, we employ an efficient network architecture with cascaded Inception blocks (CIBs) to learn rich and discriminative embeddings from patches. Experimental results on both the Bioimaging 2015 challenge dataset and the BACH dataset demonstrate our Semi-HIC method compares favorably with existing deep learning methods for histopathological image classification and consistently outperforms the semi-supervised LA method.

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