Fabrication and properties of pressure-sintered reaction-bonded Si3N4 ceramics with addition of Eu2O3–MgO–Y2O3

Dense pressure-sintered reaction-bonded Si₃N₄ (PSRBSN) ceramics were obtained by a hot-press sintering method. Precursor Si powders were prepared with Eu₂O₃–MgO–Y₂O₃ sintering additive. The addition of Eu₂O₃–MgO–Y₂O₃ was shown to promote full nitridation of the Si powder. The nitrided Si₃N₄ particles had an equiaxial morphology, without whisker formation, after the Si powders doped with Eu₂O₃–MgO–Y₂O₃ were nitrided at 1400 °C for 2 h. After hot pressing, the relative density, Vickers hardness, flexural strength, and fracture toughness of the PSRBSN ceramics, with 5 wt% Eu₂O₃ doping, were 98.3 ± 0.2%, 17.8 ± 0.8 GPa, 697.0 ± 67.0 MPa, and 7.3 ± 0.3 MPa m^1/2, respectively. The thermal conductivity was 73.6 ± 0.2 W m^?1 K^?1, significantly higher than the counterpart without Eu₂O₃ doping, or with ZrO₂ doping by conventional methods.     

Pressure and temperature dependence of second-order elastic constants from third-order elastic constants in TMC (TM=Nb,Ti, V,Zr)

In this paper, we present an efficient and effective method to predict the pressure dependence and temperature dependence of second-order elastic constants (SOECs) by introducing third-order elastic constants (TOECs) in the monocarbide ultrahigh temperature ceramics. The method is validated by comparing with experiments and previous calculations in four TMCs (TM = Nb, Ti, V, Zr). Using this method, we investigate the derivatives of SOECs against pressure and temperature as well as the anisotropic properties of polycrystalline modulus. In addition, we fit the SOECs with pressure and temperature under the framework of CALPHAD for practice usage.     

Comparative Analysis of Platelet-Derived Extracellular Vesicles Using Flow Cytometry and Nanoparticle Tracking Analysis

Growing interest in extracellular vesicles (EVs) has prompted the advancements of protocols for improved EV characterization. As a high-throughput, multi-parameter, and single particle technique, flow cytometry is widely used for EV characterization. The comparison of data on EV concentration, however, is hindered by the lack of standardization between different protocols and instruments. Here, we quantified EV counts of platelet-derived EVs, using two flow cytometers (Gallios and CytoFLEX LX) and nanoparticle tracking analysis (NTA). Phosphatidylserine-exposing EVs were identified by labelling with lactadherin (LA). Calibration with silica-based fluorescent beads showed detection limits of 300 nm and 150 nm for Gallios and CytoFLEX LX, respectively. Accordingly, CytoFLEX LX yielded 40-fold higher EV counts and 13-fold higher counts of LA⁺CD41⁺ EVs compared to Gallios. NTA in fluorescence mode (F-NTA) demonstrated that only 9.5% of all vesicles detected in scatter mode exposed phosphatidylserine, resulting in good agreement of LA⁺ EVs for CytoFLEX LX and F-NTA. Since certain functional characteristics, such as the exposure of pro-coagulant phosphatidylserine, are not equally displayed across the entire EV size range, our study highlights the necessity of indicating the size range of EVs detected with a given approach along with the EV concentration to support the comparability between different studies.     

Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids

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.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.     

药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

Dual effect synergistically triggered Ce:(Y,Tb)3(Al,Mn)5O12 transparent ceramics enabling a high color-rendering index and excellent thermal stability for white LEDs

Ce:Y₃Al₅O₁₂ transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce³⁺ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)₃(Al,Mn)₅O₁₂ TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb³⁺ and Mn²⁺ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb³⁺ ion and the energy transfer between Ce³⁺ and Mn²⁺ ions were verified in prepared TCs.     

Understanding the asymmetric perceptions of smartphone security from security feature perspective: A comparative study

Smartphones are being used and relied on by people more than ever before. The open connectivity brings with it great convenience and leads to a variety of risks that cannot be overlooked. Smartphone vendors, security policy designers, and security application providers have put a variety of practical efforts to secure smartphones, and researchers have conducted extensive research on threat sources, security techniques, and user security behaviors. Regrettably, smartphone users do not pay enough attention to mobile security, making many efforts futile. This study identifies this gap between technology affordance and user requirements, and attempts to investigate the asymmetric perceptions toward security features between developers and users, between users and users, as well as between different security features. These asymmetric perceptions include perceptions of quality, perceptions of importance, and perceptions of satisfaction. After scoping the range of smartphone security features, this study conducts an improved Kano-based method and exhaustively analyzes the 245 collected samples using correspondence analysis and importance satisfaction analysis. The 14 security features of the smartphone are divided into four Kano quality types and the perceived quality differences between developers and users are compared. Correspondence analysis is utilized to capture the relationship between the perceived importance of security features across different groups of respondents, and results of importance-satisfaction analysis provide the basis for the developmental path and resource reallocation strategy of security features. This article offers new insights for researchers as well as practitioners of smartphone security.     

Single-Cell Microgels for Diagnostics and Therapeutics

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.