We have previously developed several kinds of rapamycin-encapsulated nanoparticles to achieve sustained release of rapamycin to treat hemangioma. However, lack of intrinsic targeting and easy ...clearance by the immune system are major hurdles that artificial fabricated nanoparticles must overcome. We constructed rapamycin-encapsulated macrophage-derived exosomes mimic nanoparticles-in-microspheres (RNM), to achieve the goal of continuous targeted therapy of hemangiomas. The rapamycin-encapsulated exosome mimic nanoparticles (RN) were firstly prepared by the extrusion-based method from the U937 cells (the human macrophage cell line). After then, RN was encapsulated with PLGA (poly(lactic-co-glycolic acid)) microspheres to obtain RNM. The release profile, targeting activity, and biological activity of RN and RNM were investigated on hemangioma stem cells (HemSCs). RN has a size of 100 nm in diameter, with a rapamycin encapsulation efficacy (EE) of 83%. The prepared microspheres RNM have a particle size of ~30 µm), and the drug EE of RNM is 34%. The sustained release of RNM can remarkably be achieved for 40 days. As expected, RN and RNM showed effective inhibition of cellular proliferation, significant cellular apoptosis, and remarkable repressed expression of angiogenesis factors in HemSCs. Our results showed that RNM is an effective approach for prolonged and effective delivery of rapamycin to hemangiomas.
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•Rapamycin-encapsulated exosome-mimetic nanoparticles-in-PLGA microspheres (RNM) show slow-release of rapamycin.•RNM achieved superior therapeutic efficacy against hemangiomas over rapamycin.•The therapeutic efficacy of RNM was attributed to its sustained release and suppression efficacy against HemSCs.
Experimental results, based on two-dimensional (2-D) laboratory tests, for impulse waves generated by subaerial landslides of combined solid block and granular materials are presented in this study. ...The results are compared with those of individual models of pure solid block and granular landslides. By considering an identical slide mass and release height, the effect of the mass ratio m* on wave generation was investigated. The mass ratio is defined as m* = MB/M, where MB is the mass of the solid block, M = MB + MG is the total mass and MG is the mass of the granular portion. The experimental results show that the combined landslides with m* = 0.6 and 0.8 in this study generally produce much larger impulse waves in the impact zone compared with those triggered by pure solid block landslides (m* = 1) and pure granular landslides (m* = 0). This suggests that the primary wave amplitudes of impulse waves might have been underestimated in previous laboratory tests with solely solid or granular assemblies when using the same slide mass and release height. The larger primary wave amplitudes of the combined landslides compared with those of the pure solid block landslides are mainly attributed to the relatively large thickness of the combined landslides and the continuous motion of the granular portion, as the inside solid block stops at the hill slope toe. Compared with pure granular landslides, combined landslides generally have a larger Froude number and slide thickness, which account for the larger primary wave amplitudes. The latter plays a quantifiably more important role – nearly two times that of the former. The effects of the hill slope angle α, and the grain size of the granular materials D, were also studied in this work. Four different hill slope angles (α = 22.5°, 30°, 37.5° and 45°) and four different mean grain diameters (D = 5 mm, 10 mm, 20 mm and 30 mm) were tested. By comparing the measured maxima of the wavelet spectra obtained via a wavelet transform method with those reconstructed by means of the phase celerity of the solitary wave cs and the group celerity of linear wave cg(f), it is found that the measured maxima travel at either cs or cg(f), depending on the landslide type and the hill slope angle α. However, the celerity of the measured maxima for the high frequency is lower than cg(f) and cs for the impulse waves generated by combined landslides when α ≤ 37.5° in this study. Further investigations show that the wave amplitude decreases rapidly during wave propagation, following an exponential function. The decrease in the wave amplitude during propagation is mainly attributed to dispersion.
•Impulse waves generated by combined block-granular landslides were investigated experimentally.•The effects of the mass ratio, hill slope angle and grain size on primary wave amplitudes were examined.•Block/granular landslide may underestimate waves if real landslides consist of block and grain materials with the same mass and release height.
Biological ion channels, as fundamental units participating in various daily behaviors with incredible mass transportation and signal transmission, triggered booming researches on manufacturing their ...artificial prototypes. Biomimetic ion channel with the nanometer scale for smart responding functions has been successfully realized in sorts of materials by employing state-of-art nanotechnology. Ion track-etching technology, as crucial branches of fabricating solid-state nanochannels, exhibits outstanding advantages, such as easy fabrication, low cost, and high customization. To endow the nanochannel with smart responsibility, various modification methods are developed, including chemical grafting, non-covalent adsorption, and electrochemical deposition, enriching the reservoir of accessible stimuli-responses combinations, whereas were limited by their relatively lengthy and complex procedure. Here, based on the electric field induced self-assembly of polyelectrolytes, a universal customizable modifying strategy has been proposed, which exhibits superiorities in their functionalization with convenience and compatibility. By using this protocol, the channels’ ionic transport behaviors could be easily tuned, and even the specific ionic or molecular responding could be realized with superior performance. This strategy surely accelerates the nanochannels functionalization into fast preparing, high efficiency, and large-scale application scenarios.
S100 calcium-binding protein 16 (S100A16) is implicated in both chronic kidney disease (CKD) and acute kidney injury (AKI). Previous research has shown that S100A16 contributes to AKI by facilitating ...the ubiquitylation and degradation of glycogen synthase kinase 3β (GSK3β) and casein kinase 1α (CK1α) through the activation of HMG-CoA reductase degradation protein 1 (HRD1). However, the mechanisms governing S100A16-induced HRD1 activation and the upregulation of S100A16 expression in renal injury are not fully understood. In this study, we observed elevated expression of Hypoxia-inducible Factor 1-alpha (HIF-1α) in the kidneys of mice subjected to ischemia-reperfusion injury (IRI). S100A16 deletion attenuated the increased HIF-1α expression induced by IRI. Using a S100A16 knockout rat renal tubular epithelial cell line (NRK-52E cells), we found that S100A16 knockout effectively mitigated apoptosis during hypoxic reoxygenation (H/R) and cell injury induced by TGF-β1. Our results revealed that H/R injuries increased both protein and mRNA levels of HIF-1α and HRD1 in renal tubular cells. S100A16 knockout reversed the expressions of HIF-1α and HRD1 under H/R conditions. Conversely, S100A16 overexpression in NRK-52E cells elevated HIF-1α and HRD1 levels. HIF-1α overexpression increased HRD1 and β-catenin while decreasing GSK-3β. HIF-1α inhibition restored HRD1 and β-catenin upregulation and GSK-3β downregulation by cellular H/R injury. Notably, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated HIF-1α binding signals on the HRD1 promoter, and luciferase reporter gene assays confirmed HIF-1α's transcriptional regulation of HRD1. Additionally, we identified Transcription Factor AP-2 Beta (TFAP2B) as the upregulator of S100A16. ChIP and luciferase reporter assays confirmed TFAP2B as a transcription factor for S100A16. In summary, this study identifies TFAP2B as the transcription factor for S100A16 and demonstrates HIF-1α regulation of HRD1 transcription within the S100A16-HRD1-GSK3β/CK1α pathway during renal hypoxia injury. These findings provide crucial insights into the molecular mechanisms of kidney injury, offering potential avenues for therapeutic intervention.
Extracellular ATP (eATP), released as a "danger signal" by injured or stressed cells, plays an important role in the regulation of immune responses, but the relationship between ATP release and ...innate immune responses is still uncertain. In this study, we demonstrated that ATP was released through Toll-like receptor (TLR)-associated signaling in both Escherichia coli-infected mice and lipopolysaccharide (LPS)- or Pam3CSK4-treated macrophages. This ATP release could be blocked completely only by N-ethylmaleimide (NEM), not by carbenoxolone (CBX), flufenamic acid (FFA), or probenecid, suggesting the key role of exocytosis in this process. Furthermore, LPS-induced ATP release could also be reduced dramatically through suppressing calcium mobilization by use of U73122, caffeine, and thapsigargin (TG). In addition, the secretion of interleukin-1β (IL-1β) and CCL-2 was enhanced significantly by ATP, in a time- and dose-dependent manner. Meanwhile, macrophage-mediated phagocytosis of bacteria was also promoted significantly by ATP stimulation. Furthermore, extracellular ATP reduced the number of invading bacteria and protected mice from peritonitis by activating purinergic receptors. Mechanistically, phosphorylation of AKT and ERK was overtly increased by ATP in antibacterial immune responses. Accordingly, if we blocked the P2X- and P2Y-associated signaling pathway by using suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid), tetrasodium salt (PPADS), the ATP-enhanced immune response was restrained significantly. Taken together, our findings reveal an internal relationship between danger signals and TLR signaling in innate immune responses, which suggests a potential therapeutic significance of calcium mobilization-mediated ATP release in infectious diseases.
The unsupervised image-to-image translation aims at finding a mapping between the source ( A ) and target ( B ) image domains, where in many applications aligned image pairs are not available at ...training. This is an ill-posed learning problem since it requires inferring the joint probability distribution from marginals. Joint learning of coupled mappings F A B : A → B and F B A : B → A is commonly used by the state-of-the-art methods, like CycleGAN to learn this translation by introducing cycle consistency requirement to the learning problem, i.e., F A B ( F B A ( B ) ) ≈ B and F B A ( F A B ( A ) ) ≈ A . Cycle consistency enforces the preservation of the mutual information between input and translated images. However, it does not explicitly enforce F B A to be an inverse operation to F A B . We propose a new deep architecture that we call invertible autoencoder (InvAuto) to explicitly enforce this relation. This is done by forcing an encoder to be an inverted version of the decoder, where corresponding layers perform opposite mappings and share parameters. The mappings are constrained to be orthonormal. The resulting architecture leads to the reduction of the number of trainable parameters (up to 2 times). We present image translation results on benchmark datasets and demonstrate state-of-the art performance of our approach. Finally, we test the proposed domain adaptation method on the task of road video conversion. We demonstrate that the videos converted with InvAuto have high quality and show that the NVIDIA neural-network-based end-to-end learning system for autonomous driving, known as PilotNet, trained on real road videos performs well when tested on the converted ones.
Soilless cultivation of vegetables is widely used in production. It is also well accepted that digested slurry is frequently applied as a fertilizer in agricultural production. However, the effect of ...digested pig slurry on yield and quality of tomato soilless cultivation, as well as the yield and quality influenced by plant carbohydrate metabolism, remain unexplored. Here, the dual inputs of fertilizers (digested pig slurry (D) and mineral fertilizer (M)) and soilless substrates (peat substrate (P) and cinder substrate(C)) consisted of four treatments. The dry biomass and fruit yields, photosynthetic parameters, carbohydrate contents and metabolism enzymes in leaves and fruits were recorded during the experimental period. The highest fruit yields were obtained in DP and MP treatments. Although DP treatment significantly increased the fresh weight of single fruits by 18.0% compared to MP treatment, it reduced the number of ripe fruits. The photosynthetic efficiency and carbohydrate contents (sucrose, glucose and fructose) in leaves were generally higher in DP treatment compared to other treatments, as well as the activities of sucrose phosphate synthase and AGPase in leaves. The soluble sugar contents of fruits in DP and DC treatments were enhanced by 12.3% and 37.0%, respectively, compared to MP and MC treatments. Moreover, the current results showed that DP treatment significantly increased the activity of acid invertase in fruit by 36.3%, 31.3%, and 42.2%, respectively, compared to MP, DC, and MC treatments, and decreased the activity of AGPase by 24.2%, 16.0%, and 36.4%, respectively. The current results have demonstrated that DP treatment had better yield and quality, owing to digested pig slurry increasing the photosynthetic efficiency and source strength, and regulated the activities of carbohydrate metabolism enzymes.
This study aims to comprehensively investigate the effects of hot-air dehydration on the quality of blue honeysuckle berries (
L.). The results demonstrated that drying with hot air at 40-65 °C for ...7-72 h resulted in blue honeysuckle berries with a moisture content of 0.21-1.10 g H
O/g dry weight. Generally, low to medium temperatures (40-55 °C) showed a better effect on the quality than high temperatures (60-65 °C). Specifically, drying at 40 °C exclusively resulted in better retention of cuticular wax, the best sensory appearance, and the highest total phenolic content. Drying at 45 °C and 50 °C resulted in the highest antioxidant capacity and the optimal sensory flavor. Drying at 55 °C led to the highest soluble solid/acid ratio, ascorbic acid concentration, total flavonoid, and total anthocyanin. The work introduces an innovative raw berry product and provides a comprehensive practical and theoretical framework for convective dehydration of blue honeysuckle berries.
Nanopores in two-dimensional (2D) membranes hold immense potential in single-molecule sensing, osmotic power generation, and information storage. Recent advances in 2D nanopores, especially on ...single-layer MoS
, focus on the scalable growth and manufacturing of nanopore devices. However, there still remains a bottleneck in controlling the nanopore stability in atomically thin membranes. Here, we evaluate the major factors responsible for the instability of the monolayer MoS
nanopores. We identify chemical oxidation and delamination of monolayers from their underlying substrates as the major reasons for the instability of MoS
nanopores. Surface modification of the substrate and reducing the oxygen from the measurement solution improves nanopore stability and dramatically increases their shelf-life. Understanding nanopore growth and stability can provide insights into controlling the pore size, shape and can enable long-term measurements with a high signal-to-noise ratio and engineering durable nanopore devices.
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