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A key factor affecting the energy storage performance of antiferroelectric materials is their electrical breakdown strength. Nanocomposition is one of the effective methods to improve the electrical breakdown strength of dielectric thin films. In this study, PbZrO3‒Al2O3 nanoparticle composite films were prepared by combining chemical solution deposition of PbZrO3 and vacuum evaporation deposition of Al, and the influence of size and distribution of Al2O3 nanoparticles (NPs) on electrical properties was investigated. The results show that the Al2O3 NPs are distributed in a layered form on the PZO matrix, and their distribution can be controlled by changing the thickness of PZO coatings. As the coating thickness decreases and the coating interface increases, the distribution of Al2O3 NPs becomes more uniform, resulting in a significant increase in maximum polarization and electrical breakdown strength, and a decrease in leakage current density, thereby enhancing the energy storage performance of the PbZrO3-Al2O3 composite films. The results indicate that the regulation of the microstructure of dielectric composite films is of great significance for improving their energy storage performance. Highlights: PbZrO3‒Al2O3 nanoparticle composite films were prepared by combining chemical solution deposition of PbZrO3 and vacuum evaporation deposition of Al. The distribution of Al2O3 NPs can be controlled by changing the thickness of the PbZrO3 coating. The energy storage performance of the PbZrO3-Al2O3 composite films can be effectively improved by adjusting the distribution of Al2O3 NPs. [ABSTRACT FROM AUTHOR]

Acoustic tweezing cytometry (ATC) is an ultrasound-based biophysical technique that has shown the capability to promote differentiation of human pluripotent stem cells (hPSCs). This study systematically examined how hPSCs respond to cyclic mechanical strains applied by ATC via displacement of integrin-bound microbubbles (averaged diameter of 4.3 µm) using ultrasound pulses (acoustic pressure 0.034 MPa, center frequency 1.24 MHz and pulse repetition frequency 1 Hz). Our data show downregulation of pluripotency marker Octamer-binding transcription factor 4 (OCT4) by at least 10% and increased nuclear localization of Yes-associated protein (YAP) by almost 100% in hPSCs immediately after ATC application for as short as 1 min and 5 min respectively. Analysis of the movements of integrin-anchored microbubbles under ATC stimulations reveals different stages of viscoelastic characteristic behavior and increasing deformation of the integrin-cytoskeleton (CSK) linkage. The peak displacement of integrin-bound microbubbles increased from 1.45 ± 0.16 to 4.74 ± 0.67 μm as the duty cycle of ultrasound pulses increased from 5% to 50% or the duration of each ultrasound pulse increased from 0.05 to 0.5 s. Real-time tracking of integrin-bound microbubbles during ATC application detects high correlation of microbubble displacements with OCT4 downregulation in hPSCs. Together, our data showing fast downregulation of OCT4 in hPSCs in respond to ATC stimulations highlight the unique mechanosensitivity of hPSCs to integrin-targeted cyclic force/strain dependent on the pulse duration or duty cycle of ultrasound pulses, providing insights into the mechanism of ATC-induced accelerated differentiation of hPSCs. [ABSTRACT FROM AUTHOR]

Hyperactivation of hypothalamic–pituitary–adrenal (HPA) axis and hypothalamic–pituitary–thyroid (HPT) axis were found in acute high altitude challenge, but the role of gut microbiota and metabolites is unknown. We utilized adult male Sprague–Dawley rats at a simulated altitude of 5500 m for 3 days in a hypobaric-hypoxic chamber. ELISA and metabolomic analyses of serum and 16S rRNA and metabolomic analyses of fecal samples were then performed. Compared with the normoxic group, serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and thyroxine (tT4) were increased in the hypoxia group, whereas thyrotropin-releasing hormone (TRH) was decreased. Bacteroides, Lactobacillus,Parabacteroides,Butyricimonas,SMB53,Akkermansia,Phascolarctobacterium, and Aerococcus were enriched in hypoxia group, whereas [Prevotella], Prevotella,Kaistobacter,Salinibacterium, and Vogesella were enriched in normoxic group. Metabolomic analysis indicated that acute hypoxia significantly affected fecal and serum lipid metabolism. In addition, we found five fecal metabolites may mediate the cross-talk between TRH, tT4, and CORT with [Prevotella], Kaistobacter,Parabacteroides, and Aerococcus, and 6 serum metabolites may mediate the effect of TRH and tT4 on [Prevotella] and Kaistobacter by causal mediation analysis. In conclusion, this study provides new evidence that key metabolites mediate the cross-talk between gut microbiota with HPA and HPT axis under acute hypobaric hypoxia challenge. [ABSTRACT FROM AUTHOR]

Background: Minimal change disease (MCD) is the major cause of childhood idiopathic nephrotic syndrome, which is characterized by massive proteinuria and debilitating edema. Proteinuria in MCD is typically rapidly reversible with corticosteroid therapy, but relapses are common, and children often have many adverse events from the repeated courses of immunosuppressive therapy. The pathobiology of MCD remains poorly understood. Prior clinical observations suggest that abnormal T-cell function may play a central role in MCD pathogenesis. Based on these observations, we hypothesized that T-cell responses to specific exposures or antigens lead to a clonal expansion of T-cell subsets, a restriction in the T-cell repertoire, and an elaboration of specific circulating factors that trigger disease onset and relapses. Methods: To test these hypotheses, we sequenced T-cell receptors in fourteen MCD, four focal segmental glomerulosclerosis (FSGS), and four membranous nephropathy (MN) patients with clinical data and blood samples drawn during active disease and during remission collected by the Nephrotic Syndrome Study Network (NEPTUNE). We calculated several T-cell receptor diversity metrics to assess possible differences between active disease and remission states in paired samples. Results: Median productive clonality did not differ between MCD active disease (0.0083; range: 0.0042, 0.0397) and remission (0.0088; range: 0.0038, 0.0369). We did not identify dominant clonotypes in MCD active disease, and few clonotypes were shared with FSGS and MN patients. Conclusions: While these data do not support an obvious role of the adaptive immune system T-cells in MCD pathogenesis, further study is warranted given the limited sample size. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Tenebenal, as a new insecticide, with a novel action mode, has shown an excellent insecticidal effect, but there is no relevant report about how it can effectively control termite colonies. In this study, we evaluated the insecticidal effects of tenebenal at different concentrations by laboratory study, including the contact toxicity, stomach toxicity, and other insecticide effects of Reticulitermes flaviceps. The results showed that tenebenal had no repellent effect on R. flaviceps in concentrations ranging from 0 to 32 ppm. LC50 and LC90 of tenebenal on R. flaviceps were 3.752 and 8.278 ppm when treating termites with tenebenal for 24 h, respectively. The survival rate and food consumption of R. flaviceps significantly decreased with the increase of the tenebenal concentration from 1 to 8 ppm, and there was no significant difference in concentration between 8 and 16 ppm. Tenebenal had inhibitive effects on particle transfer, tunneling, carcass-burying, and cannibalism behavior of R. flaviceps with concentrations from 1 to 16 ppm. R. flaviceps are exposed to sand treatment with 16, 32, and 64 ppm of tenebenal for 1 h, and the mortality for both donor and recipient is 36%, 77%, and 100% on day 3, respectively. These results show that tenebenal has potential insecticidal effects and could be a new termiticide for termite control. [ABSTRACT FROM AUTHOR]

High levels of S100A6 have been associated with poor outcome in some types of human cancers, but the role of S100A6 in the molecular pathogenesis of these cancers is largely unknown. This study was performed to explore the expression and functional roles of S100A6 in hepatocellular carcinoma (HCC). The expression level of S100A6 in HCC tumor and corresponding peritumoral tissues were determined by immunohistochemistry analysis. The potential functions of S100A6 in tumorigenesis and metastasis were analyzed by cell proliferation, migration, and invasion assays in human liver cancer cells. Moreover, through expression and purification of S100A6 recombinant protein tagged with cell-penetrating peptide, we analyzed its complex extracellular/intracellular effects in a S100A6-silenced cellular model. As a result, the expression of S100A6 was up-regulated in human HCC compared with adjacent peritumoral tissues. S100A6 silencing inhibited the growth and motility of HCC cells, while intracellular re-expression of S100A6 could rescue the proliferation and migration defects. Intracellular over-expression of S100A6 resulted in down-regulation of E-cadherin expression and promoted nuclear accumulation of β-catenin. Moreover, we found that the enhanced cell proliferation and motility after S100A6 stimulation were dependent on the activation of PI3K/AKT pathway. These results suggest that S100A6 may be involved in promotion and progression of human liver cancer. Key Messages: [ABSTRACT FROM AUTHOR]

Safety is the foremost issue in all human cell therapies, but human induced pluripotent stem cells (iPSCs) currently lack a useful safety indicator. Studies in chimeric mice have demonstrated that certain lines of iPSCs are tumorigenic; however a similar screen has not been developed for human iPSCs. Here, we show that in vitro cartilage tissue engineering is an excellent tool for screening human iPSC lines for tumorigenic potential. Although all human embryonic stem cells (ESCs) and most iPSC lines tested formed cartilage safely, certain human iPSCs displayed a pro-oncogenic state, as indicated by the presence of secretory tumors during cartilage differentiation in vitro.We observed five abnormal iPSC clones amoungst 21 lines derived from five different reprogramming methods using three cellular origins. We conclude that in vitro cartilage tissue engineering is a useful approach to identify abnormal human iPSC lines. [ABSTRACT FROM AUTHOR]

Thymidylate synthase (TS) is a critical enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite eflicient and encouraging as antitumor drugs. In this paper, the binding model of 14 antifolates of substituted benzylamino- and heterocyclylmethylamino-carbodithioate derivatives of 4-(3H)-quinazolinone with TS is examined using molecular simulation methods—FlexiDock and SCORE2.0. The resulting conformation and orientation of these antifolates are directly applied to CoMFA study. The robust QSAR model, its three-dimensional contour map, and binding score of these antifolates derived from SCORE2.0 provide guidelines for structural optimization of current antifolates. The experiment indicates that deletion of cancer chemopreventive structure of dithiocarbamate is unfavorable for interaction between TS and antifolates. [ABSTRACT FROM AUTHOR]

Protein kinase catalyzes the transfer of the y-phosphoryl group from ATP to the hydroxyl groups of protein side chains, which plays critical roles in signal transduction pathways by transmitting extracellular signals across the plasma membrane and nuclear membrane to the destination sites in the cytoplasm and the nucleus. Protein kinase C (PKC) is a superfamily of phospholipid-dependent Ser/Thr kinase. There are at least 12 isozymes in PKC family. They are distributed in different tissues and play different roles in physiological processes. On account of their concern with a variety of pathophysiologic states, such as cancer, inflammatory conditions, autoimmune disorder, and cardiac diseases, the inhibitors, which can inhibit the activity of PKC and the interaction of cytokine with receptor, and interfere signal transduction pathway, may be candidates of therapeutic drugs. Therefore, intense efforts have been made to develop specific protein kinase inhibitors as biological tools and therapeutic agents. This article reviews the recent development of some of PKC inhibitors based on their interaction with different conserved domains and different inhibition mechanisms. [ABSTRACT FROM AUTHOR]

Under the impact of climatic warming, the glaciers in the High Asia in China have been retreating continuously with negative glacial mass balance in recent several decades. The retreat became more intensive in the past 10 years. The spatial pattern of the glacial retreat in the High Asia in China is that the smallest magnitude of retreat is in the inland of the Tibetan Plateau, the magnitude increases from the inland to the margin of the Tibetan Plateau, and the largest magnitude at the margin of the Tibetan Plateau. The glacial retreat in the High Asia in China has an important impact on the water resource of the arid regions in Northwest China. This study shows that the glacial retreat in the 1990s has caused an increase of 5.5% in river runoff in Northwest China. In the Tarim River basin, the increase of river runoff is higher than 5.5%. [ABSTRACT FROM AUTHOR]

Due to their ability to standardize key physiological parameters, stirred suspension bioreactors can potentially scale the production of quality-controlled pluripotent stem cells (PSCs) for cell therapy application. Because of differences in bioreactor expansion efficiency between mouse (m) and human (h) PSCs, we investigated if conversion of hPSCs, from the conventional "primed" pluripotent state towards the "naïve" state prevalent in mPSCs, could be used to enhance hPSC production. Through transcriptomic enrichment of mechano-sensing signaling, the expression of epigenetic regulators, metabolomics, and cell-surface protein marker analyses, we show that the stirred suspension bioreactor environment helps maintain a naïve-like pluripotent state. Our research corroborates that converting hPSCs towards a naïve state enhances hPSC manufacturing and indicates a potentially important role for the stirred suspension bioreactor's mechanical environment in maintaining naïve-like pluripotency. Rohani et al show that converting human pluripotent stem cells (hPSCs) to the naïve state enhances hPSC manufacturing. Further, through transcriptomics, the expression of epigenetic regulators, metabolomics, and cell-surface protein marker analyses, they indicate a potentially important role for the stirred bioreactor's mechanical environment in maintaining naïve-like pluripotency. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) are typically derived in adherent culture. Here we report fast and efficient derivation of mouse iPSCs in stirred suspension bioreactors, with and without the use of c-Myc. Suspension-reprogrammed cells expressed pluripotency markers, showed multilineage differentiation in vitro and in vivo, and contributed to the germline in chimeric mice. Suspension reprogramming has the potential to accelerate and standardize iPSC research. [ABSTRACT FROM AUTHOR]

In this paper, Al-CaB6 alloys were prepared by in situ melt reaction. The CaB6 particles through in situ growth are cubic with a regular shape, evenly distributed in the Al matrix. By edge-to-edge matching model’s calculation, mismatch between CaB6 particles and α-Al was ~2.34%, which is less than 6%, so CaB6 can serve as the core of α-Al nucleation. When the amount of CaB6 addition reaches 6 wt.%, hardness of the Al-CaB6 alloy reached 34.4 HV. Besides, CaB6-particle reinforced hypereutectic Al-Si composites were prepared, and the positive influence of CaB6 particles on microstructure and properties of hypereutectic Al-Si composites was studied. The CaB6 particles show significant effect on the modification of primary silicon. Owing to the addition of CaB6 particles, the hardness of hypereutectic Al-Si alloys increased and the hardness of Al-18Si-CaB6 reached 95.1 HV. The electrochemical test of the manufactured composites revealed that the corrosion resistance of Al-18Si-CaB6 composites improved as the amount of CaB6 particle content increased. This work serves as a reference for the investigation of Al and Al-Si composites reinforced with ceramic particles. [ABSTRACT FROM AUTHOR]