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Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI50) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC50) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI50 level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI50 level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.  相似文献   
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In flotation, metal ions possess significant roles that are usually fulfilled by either selectively activating or depressing the target minerals. Despite that tremendous efforts have been made to address the roles of metal ions in flotation, it still lacks a comprehensive review, especially to compare various ions instead of focusing on a specific one. This review begins by elaborately categorizing the factors involved in affecting the roles of metal ions in flotation. After that, well-accepted mechanisms are updated and discussed from the ore type. Furthermore, typical approaches to explore the underlying mechanisms are emphasized, including traditional techniques such as micro-flotation, contact angle measurement, zeta potential measurement, and other recent prevailing methodologies, like computational method, solution chemistry calculation, and cyclic voltammetry. This work will pave the way to promote flotations via activities like selectively adding/reducing metal ions, choosing reagents, and regulating the slurry chemistry.  相似文献   
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The influence of high concentration Zn2+ on the floatability of sphalerite in an acidic system was investigated via flotation experiments, zeta potential measurements, contact angle measurements, and X-ray photoelectron spectroscopy. The results indicated that Zn2+ was adsorbed on the sphalerite surface and a Zn-hydroxyl complex was formed at a pH of 4 and a Zn2+ concentration of 4×10−2 mol/L. The zeta potential increased and the contact angle decreased from 84.80° to 36.48°, strongly inhibiting the floatability of sphalerite. When S2− or Cu2+ activator was used alone, sphalerite was not activated after Zn2+ was adsorbed, and its contact angle did not change significantly. However, by using a combination of S2− and Cu2+ activators, its floatability was realized after Zn2+ adsorption. This result was attributed to the removal of the Zn-hydroxyl complex on the surface of sphalerite by S2−. After this removal, Cu2+ was adsorbed on the sphalerite surface to form a Cu2S·S0 hydrophobic film.  相似文献   
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The ability to trap precise quantities of cells or particles into confined areas has numerous applications for biological purposes. In particular, single cell trapping has received considerable attention because it permits the study of heterogeneity in a population, while trapping larger groups of cells have been used to form aggregates. Among several methods, the use of microwell offers a simple platform to capture cells or particles using hydrodynamic forces. This review examines the use of microwells in both static and microfluidic environments, and the application of microfluidic geometric arrays for trapping. This paper discusses the design and fabrication methods of microwells and compares the trapping and release techniques used in both static and microfluidics‐integrated microwells. Finally, we will summarize novel microfluidic geometric arrays used to capture cells or particles through hydrodynamic trapping.  相似文献   
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Cell encapsulation within hydrogel droplets is transforming what is feasible in multiple fields of biomedical science such as tissue engineering and regenerative medicine, in vitro modeling, and cell-based therapies. Recent advances have allowed researchers to miniaturize material encapsulation complexes down to single-cell scales, where each complex, termed a single-cell microgel, contains only one cell surrounded by a hydrogel matrix while remaining <100 μm in size. With this achievement, studies requiring single-cell resolution are now possible, similar to those done using liquid droplet encapsulation. Of particular note, applications involving long-term in vitro cultures, modular bioinks, high-throughput screenings, and formation of 3D cellular microenvironments can be tuned independently to suit the needs of individual cells and experimental goals. In this progress report, an overview of established materials and techniques used to fabricate single-cell microgels, as well as insight into potential alternatives is provided. This focused review is concluded by discussing applications that have already benefited from single-cell microgel technologies, as well as prospective applications on the cusp of achieving important new capabilities.  相似文献   
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Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1G227R and NEU1V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1G227R- and NEU1V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1G227R- and NEU1V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.  相似文献   
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