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Stem cell transplantation provides a promising approach for addressing inflammation and functional disorders. Nonetheless, the viability of these transplanted cells diminishes significantly within pathological environments, limiting their therapeutic potential. Moreover, the non-invasive tracking of these cells in vivo remains a considerable challenge, hampering the assessment of their therapeutic efficacy. Transition-metal oxide nanocrystals, known for their unique "enzyme-like" catalytic property and imaging capability, provide a new avenue for clinical application. In this study, the lignin as a biocompatible macromolecule was modified with poly (ethylene glycol) through chain-transfer polymerization, and then it was utilized to incorporate superparamagnetic iron oxide and cerium oxide nanocrystals creating a functional nanozyme. The iron oxide nanocrystals self-assembled into the hydrophobic core of nano system, while the in-situ mineralization of cerium oxide particles was carried out with the assistance of peripheral phenolic hydroxyl groups. The product, ceriumiron core-shell nanozyme, enabled effective stem cells labeling through endocytosis and exhibited catalase and superoxide dismutase activities within the cells. As a result, it could scavenge highly destructive hydroxyl radicals and peroxyl radicals, shielding stem cells from apoptosis in inflammatory environment and maintaining their differentiation ability. Additionally, when these functionalized stem cells were administered to mice with acute inflammation, not only did they alleviate disease symptoms, but they also allowed for the visualization using T2-weighted magnetic resonance imaging. This innovative therapeutic approach provides a new strategy for combatting diseases.
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Apoptose , Cério , Inflamação , Lignina , Imageamento por Ressonância Magnética , Cério/química , Cério/farmacologia , Animais , Lignina/química , Lignina/farmacologia , Apoptose/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Camundongos , Transplante de Células-Tronco/métodos , Ferro/química , Humanos , Nanopartículas/química , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacosRESUMO
Cancer stem cells (CSCs) constitute a specific subset of cells found within tumors that are responsible for initiating, advancing and resisting traditional cancer treatments. M2 macrophages, also known as alternatively activated macrophages, contribute to the development and progression of cancer through their involvement in promoting angiogenesis, suppressing the immune system, supporting tumor growth and facilitating metastasis. Exosomes, tiny vesicles released by cells, play a crucial role in intercellular communications and have been shown to be associated with cancer development and progression by influencing the immune response; thus, they may serve as markers for diagnosis and prognosis. Currently, investigating the impact of exosomes derived from M2 macrophages on the maintenance of CSCs is a crucial area of research with the aim of developing novel therapeutic strategies to target this process and improve outcomes for individuals with cancer. Understanding the biological functions of exosomes derived from M2 macrophages and their involvement in cancer may lead to the formulation of novel diagnostic tools and treatments for this disease. By targeting M2 macrophages and the exosomes they secrete, promising prospects emerge for cancer treatment, given their substantial contribution to cancer development and progression. Further research is required to fully grasp the intricate interactions between CSCs, M2 macrophages and exosomes in cancer, and to identify fresh targets for cancer therapy. The present review explores the pivotal roles played by exosomes derived from M2 cells in maintaining the stemlike properties of cancer cells.
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Exossomos , Neoplasias , Humanos , Macrófagos , Comunicação Celular , Células-Tronco NeoplásicasRESUMO
As a natural ecological fragile region, the vast desert steppe in the Inner Mongolia has a developed animal husbandry, and thus posed great impacts on soil quality. In order to accurately evaluate the current situation of soil quality in the desert steppe, it is therefore imperative to adopt a suitable method to effectively assess the soil quality in the region. In this study, the minimum data set (MDS) was established with the help of principal component analysis, Norm value calculation, and correlation analysis, and four indicators, including organic matter, sand grains, soil erosion degree, and pH, were established to evaluate the soil quality of the desert steppe in the Siziwang Banner, a county in the Inner Mongolia. The results from the minimum data set (MDS) method were validated based on the total data set (TDS) method, and the validation indicated that the MDS method can be representative of the soil quality of the study area. The results indicated: 1) the soil quality index (SQI) of 0-30 cm in more than 90% of the study area falls in the range of 0.4 and 0.6 (medium level), while the better level (SQI ≥0.6) only accounted less than 10% of the study area; 2) For the MDS indexes, soil organic matter content at all depths decreased in the southern mountains, central hills, and northern plateau, which is consistent with the changing trends of SQI; 3) The sand grain was the dominant particle in the study region, which was in accordance with the intense wind erosion; 4) The negative correlation was found between the soil pH value and SQI (the high value in pH corresponded to the low value in SQI), which reflected that soil pH has a more stressful effect on the local vegetation. Overall, the MDS indexes in this study can objectively and practically reflect the soil quality in the study area, which can provide a cost effective method for SQI assessment in the desert steppe, which is important for the further grassland ecological construction and grassland management to improve the soil quality in the desert steppes.
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Areia , Solo , Animais , Erosão do Solo , Criação de Animais Domésticos , ChinaRESUMO
The study focuses on the fault signals of rolling bearings, which are characterized by nonlinearity, periodic impact, and low signal-to-noise ratio. The advantages of entropy calculation in analyzing time series data were combined with the high calculation accuracy of Multiscale Fuzzy Entropy (MFE) and the strong noise resistance of Multiscale Permutation Entropy (MPE), a multivariate coarse-grained form was introduced, and the coarse-grained process was improved. The Composite Multivariate Multiscale Permutation Fuzzy Entropy (CMvMPFE) method was proposed to solve the problems of low accuracy, large entropy perturbation, and information loss in the calculation process of fault feature parameters. This method extracts the fault characteristics of rolling bearings more comprehensively and accurately. The CMvMPFE method was used to calculate the entropy value of the rolling bearing experimental fault data, and Support Vector Machine (SVM) was used for fault diagnosis analysis. By comparing with MPFE, the Composite Multiscale Permutation Fuzzy Entropy (CMPFE) and the Multivariate Multiscale Permutation Fuzzy Entropy (MvMPFE) methods, the results of the calculations show that the CMvMPFE method can extract rolling bearing fault characteristics more comprehensively and accurately, and it also has good robustness.
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Feruloyl esterase (FAE)-producing micro-organisms to obtain ferulic acid (FA) from natural substrates have good industrial prospects, and the synergistic effect of multiple bacteria can better improve the yield of FA. In this study, on the premise of the synergistic effect of FAE, hemicellulose, and cellulase, the key strain Klebsiella oxytoca Z28 with FAE was combined with CMCase and Xylanase-producing strains to produce FA. The combination of strains with higher FA production are Klebsiella oxytoca Z28, Klebsiella pneumoniae JZE, Bacillus velezensis G1, and their FA production can reach 109.67 µg/g, which is 15% higher than that of single bacteria. To explore the effects of temperature, Ph, inoculum amount, distillers grains concentration and fermentation time on the FAE activity of the combination of strains in the fermentation process, and determined that temperature, Ph, and fermentation time were the main influencing factors and optimized through orthogonal design. The optimized fermentation conditions are 34 °C, Ph 8.0, and fermentation days for 6 days, the FAE activity can reach 270.78 U/L, and the FA yield of the combined strain is 324.50 µg/g, which is 200% higher than that of single-strain fermentation.
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Objective: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) remains a hopeful therapeutic approach for bone defect reconstruction. Herein, we investigated the effects and mechanisms of leukemia inhibitory factor (LIF) in the function and viability of hypoxic BMSCs as well as bone defect repair. Methods: The effects of LIF on apoptosis (flow cytometry, TUNEL staining), mitochondrial activity (JC-1 staining), proliferation (colony formation, EdU staining), and differentiation (CD105, CD90, and CD29 via flow sorting) were examined in hypoxic BMSCs. LIF, LIFR, gp130, Keap1, Nrf2, antioxidant enzymes (SOD1, catalase, GPx-3), bone-specific matrix proteins (ALP, BSP, OCN), PI3K, and Akt were detected via immunoblotting or immunofluorescent staining. BMSCs combined with biphasic calcium phosphate scaffolds were implanted into calvarial bone defect mice, and the therapeutic effect of LIF on bone defect was investigated. Results: Hypoxic BMSCs had increased apoptosis and oxidative stress and reduced mitochondrial activity. Additionally, LIF, LIFR, and gp130 were upregulated and PI3K/Akt activity was depressed in hypoxic BMSCs. Upregulated LIF alleviated apoptosis and oxidative stress and heightened mitochondrial activity and PI3K/Akt signaling in hypoxic BMSCs. Additionally, LIF overexpression promoted self-renewal and osteogenic differentiation of BMSCs with hypoxic condition. Mechanically, LIF facilitated self-renewal and differentiation as well as attenuated oxidative stress of BMSCs through enhancing PI3K/AKT signaling activity. Implantation of LIF-overexpressed BMSC-loaded BCP scaffolds promoted osteogenesis as well as alleviated oxidative stress and apoptosis through PI3K/Akt signaling. Conclusion: Our findings demonstrate that LIF facilitates self-renewal and differentiation and attenuates oxidative stress of BMSCs by PI3K/AKT signaling.
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Osteogênese , Fosfatidilinositol 3-Quinases , Animais , Medula Óssea , Receptor gp130 de Citocina/metabolismo , Hipóxia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator Inibidor de Leucemia/farmacologia , Células-Tronco Mesenquimais , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Leukemia inhibitory factor (LIF) is known to play a major role in bone physiology. In the present study, we examined the in vitro effects of LIF on osteoblast differentiation of bone marrow stem cells (BMSCs) and explored in vivo effects of LIF on the bone repair capacity of BMSCs-loaded biphasic calcium phosphate (BCP) scaffolds in mouse calvarial bone defect model. The mRNA and protein expression levels in the BMSCs were determined by quantitative real-time PCR and western blot, respectively; the in vitro osteoblast differentiation of the BMSCs was evaluated by using Alizarin Red S staining. The bone volume and bone density in the repaired calvarial bone defect were determined by Micro-CT. Bone regeneration was also histologically evaluated by hematoxylin and eosin staining and Masson's trichrome staining. Hypoxia treatment induced the up-regulation of Lif mRNA and LIF protein in the BMSCs. Lif overexpression up-regulated the mRNA expression levels of osteopontin and Runt-related transcription factor 2, and increased intensity of Alizarin Red S staining in the BMSCs; while Lif silence exerted the opposite effects. The in vivo studies showed that implantation of Lif-overexpressing BMSCs-loaded BCP scaffolds significantly increased the bone volume and bone density at 4 and 8 weeks after transplantation, and promoted the regeneration of bone tissues in the mouse calvarial bone defect at 8 weeks after transplantation when compared to the BMSCs-loaded BCP scaffolds group; while Lif-silencing BMSCs-loaded BCP scaffolds had the opposite effects. The present study for the first time demonstrated that LIF promoted the in vitro osteoblast differentiation of hypoxia-treated BMSCs; and further studies revealed that LIF exerted enhanced effects on the bone repair capacity of BMSCs-load BCP scaffolds in mouse calvarial bone defect model. However, future studies are warranted to determine the detailed mechanisms of LIF in the large-scale bone defect repair.
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Regeneração Óssea/efeitos dos fármacos , Fator Inibidor de Leucemia/uso terapêutico , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Animais , Proliferação de Células , Modelos Animais de Doenças , Fator Inibidor de Leucemia/farmacologia , Masculino , CamundongosRESUMO
Schottky barrier (SB) transistors operate distinctly different from conventional metal-oxide semiconductor field-effect transistors, in a unique way that the gate impacts the carrier injection from the metal source/drain contacts into the channel region. While it has been long recognized that this can have severe implications for device characteristics in the subthreshold region, impacts of contact gating of SB in the on-state of the devices, which affects evaluation of intrinsic channel properties, have been yet comprehensively studied. Due to the fact that contact resistance (RC ) is always gate-dependent in a typical back-gated device structure, the traditional approach of deriving field-effect mobility from the maximum transconductance (gm ) is in principle not correct and can even overestimate the mobility. In addition, an exhibition of two different threshold voltages for the channel and the contact region leads to another layer of complexity in determining the true carrier concentration calculated from Q = COX * (VG -VTH ). Through a detailed experimental analysis, the effect of different effective oxide thicknesses, distinct SB heights, and doping-induced reductions in the SB width are carefully evaluated to gain a better understanding of their impact on important device metrics.
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Mesenchymal stemXin cells (MSCs) are a great cell source for bone regeneration. Although combining MSCs with growth factors and scaffolds provides a useful clinical strategy for bone tissue engineering, the efficiency of MSC osteogenic differentiation remains to be improved. Epigenetic modification is related to the differentiation ability of MSCs during osteogenic induction. In this study, we evaluate the effect of Chaetocin, an inhibitor of lysine-specific histone methyltransferases, on the differentiation of MSCs. We found that MSCs treated with Chaetocin demonstrated increased osteogenic ability and reduced adipogenic ability. The expression of osteogenic markers (Runx2 and OPN) was induced in MSCs by Chaetocin during osteogenic induction. Moveover, treatment of Chaetocin in MSCs improves Wnt/ß-catenin signaling pathways and its downstream targets. Finally, we showed increased bone formation of MSC and Wnt/ß-catenin signaling activity by treatment of Chaetocin using in vivo bone formation assays. Our data uncovered a critical role of Chaetocin in MSC osteogenic differentiation and provide new insights into bone tissue regeneration and repair.
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Iron oxide nanomaterials with mimic enzymes activity have been paid more attention in the clinical diagnosis field. The modified surface molecules would influence the catalytic activity of nanozyme, which is worth studying. Furthermore, the traditional detection strategy is based on colorimetric change of substrates, however, the optical signal is easy to be interfered in complex biological applications. In our research, an efficient and facile preparation strategy was developed to obtain functional artificial nanozymes. Herein, three kinds of surfactants, including citrate acid, poly(ethylene glycol) bis (carboxymethyl) ether and tannic acid have been applied to modify these nanomaterials that showed uniform size, high soluble dispersity and stability. Furthermore, these nanozymes exhibited different peroxidase-like activity to catalyze the hydrogen peroxide and 3,3',5,5'-tetramethylbenzidine. More importantly, magnetic relaxation effect of iron oxide nanozymes was found to be changed during the catalytic reaction. In addition, the relationship between the magnetic signal of nanozymes and the substrate concentration showed a good linear dependence. Combined with the natural enzymes, the magnetic detection of iron oxide nanozymes also exhibited excellent substrate specificity. On these bases, a dual-function specific assay was constructed and further used for glucose detection. In conclusion, this study demonstrated an efficient iron oxide nanozymes preparation method and constructed a new synergistically colorimetric-magnetic diagnosis strategy.
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Colorimetria , Compostos Férricos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância MagnéticaRESUMO
Wind and sand control features are important tools for limiting desertification. Sand barriers are one of the oldest engineering measures used to reduce wind-sand hazards. Their efficacy and exact mechanism by which they work has remained a topic of scientific debate however. Sediment grain-size distributions can help constrain their utility and function. This research analyzed sediment grain size distributions in samples collected from areas around six different types of sand barriers installed along the southeastern margin of the Tengger Desert. Results were compared with sediment from a bare dune area (no barriers) used as a control. The barrier area samples contained high proportions of coarse sand and relatively low proportions of silty sand and very fine sand. Fine and medium sand were present but clay was not. The lower proportions of fine sand and higher proportions of coarse sand relative to bare dunes documented an effective reduction in aeolian transport by the barriers. Samples from the barrier areas also showed poorer sorting relative to bare dune areas. This appeared as lower kurtosis values and wider frequency distribution curves relative to those measured from bare dunes samples. The wider cumulative frequency curves for samples from the barrier areas likely reflects the higher proportion of coarse-grained material. The Straw/1.5 and PLA/1 barrier types hosted greater sediment accumulation than that observed for the other barrier types (Straw/1, PLA/1.5, Mixed/1 and Mixed/1.5). Sediment grain size distributions showed that the base and middle slope areas of the dune experienced deposition, while the top of the dunes experienced erosion. The Straw/1 barrier (straw installed as a 1 × 1 m grid) performed best in terms of installation costs and protective effects for the study area. This study demonstrates how sediment grain size distributions can be used as quantitative proxies for sand barrier performance in reducing desertification.
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Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with COVID-19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. Interleukin-6 (IL-6), IL-10 and C-reactive protein were remarkably up-regulated in patients with severe COVID-19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-6, IL-10 and C-reactive protein are reliable indicators of severe COVID-19.
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Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Betacoronavirus/fisiologia , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Linfócitos/patologia , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Índice de Gravidade de Doença , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T Reguladores/patologiaRESUMO
Based on the careful design of two-terminal devices from multi-layer transition metal dichalcogenides (TMDs) such as MoS2 and WSe2, truly vertical transport has been experimentally evaluated and theoretically analyzed. By exploring, the electric field and temperature dependence of in total 28 TMD devices of various thicknesses, a model that describes vertical transport as Fowler Nordheim mediated at high electric fields and thermal injection dominated at low fields has been developed. Our approach is similar to the description chosen to capture gate leakage current levels through amorphous materials such as SiO2. Employing our quantitative analysis, an effective vertical transport mass of m*/m0 (MoS2) ≈ 0.18 and m*/m0 (WSe2) ≈ 0.14 has been extracted for the first time and barriers at the metal contact-to-TMD interface of heights similar to those extracted for lateral transport in TMD transistors have been confirmed.
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The key appeal of two-dimensional (2D) materials such as graphene, transition metal dichalcogenides (TMDs), or phosphorene for electronic applications certainly lies in their atomically thin nature that offers opportunities for devices beyond conventional transistors. It is also this property that makes them naturally suited for a type of integration that is not possible with any three-dimensional (3D) material, that is, forming heterostructures by stacking dissimilar 2D materials together. Recently, a number of research groups have reported on the formation of atomically sharp p/n-junctions in various 2D heterostructures that show strong diode-type rectification. In this article, we will show that truly vertical heterostructures do exhibit much smaller rectification ratios and that the reported results on atomically sharp p/n-junctions can be readily understood within the framework of the gate and drain voltage response of Schottky barriers that are involved in the lateral transport.
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As a model system to probe ligand-dependent charge transfer in complex composite heterostructures, we fabricated double-walled carbon nanotube (DWNT)-CdSe quantum dot (QD) composites. Whereas the average diameter of the QDs probed was kept fixed at â¼4.1 nm and the nanotubes analyzed were similarly oxidatively processed, by contrast, the ligands used to mediate the covalent attachment between the QDs and DWNTs were systematically varied to include p-phenylenediamine (PPD), 2-aminoethanethiol (AET), and 4-aminothiophenol (ATP). Herein, we have put forth a unique compilation of complementary data from experiment and theory, including results from transmission electron microscopy (TEM), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, Raman spectroscopy, electrical transport measurements, and theoretical modeling studies, in order to fundamentally assess the nature of the charge transfer between CdSe QDs and DWNTs, as a function of the structure of various, intervening bridging ligand molecules. Specifically, we correlated evidence of charge transfer as manifested by changes and shifts associated with NEXAFS intensities, Raman peak positions, and threshold voltages both before and after CdSe QD deposition onto the underlying DWNT surface. Importantly, for the first time ever in these types of nanoscale composite systems, we have sought to use theoretical modeling to justify and account for our experimental results. Our overall data suggest that (i) QD coverage density on the DWNTs varies, based upon the different ligand pendant groups used and that (ii) the presence of a π-conjugated carbon framework within the ligands themselves coupled with the electron affinity of their pendant groups collectively play important roles in the resulting charge transfer from QDs to the underlying CNTs.
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Mesenchymal stem cells (MSCs) have exhibited therapeutic effects in multiple animal models so that are promising liver substitute for transplantation treatment of end-stage liver diseases. However, it has been shown that over-manipulation of these cells increased their tumorigenic potential, and that reducing the in vitro culture time could minimize the risk. In this study, we used a D-galactosamine plus lipopolysaccharide (Gal/LPS)-induced acute liver failure mouse model, which caused death of about 50% of the mice with necrosis of more than 50% hepatocytes, to compare the therapeutic effects of human umbilical cord MSCs (hUCMSCs) before and after induction of differentiation into hepatocyte (i-Heps). Induction of hUCMSCs to become i-Heps was achieved by treatment of the cells with a group of growth factors within 4 weeks. The resulted i-Heps exhibited a panel of human hepatocyte biomarkers including cytokeratin (hCK-18), α-fetoprotein (hAFP), albumin (hALB), and hepatocyte-specific functions glycogen storage and urea metabolism. We demonstrated that transplantation of both cell types through tail vein injection rescued almost all of the Gal/LPS-intoxicated mice. Although both cell types exhibited similar ability in homing at the mouse livers, the populations of the hUCMSCs-derived cells, as judged by expressing hAFP, hCK-18 and human hepatocyte growth factor (hHGF), were small. These observations let us to conclude that the hUCMSCs was as effective as the i-Heps in treatment of the mouse acute liver failure, and that the therapeutic effects of hUCMSCs were mediated largely via stimulation of host hepatocyte regeneration, and that delivery of the cells through intravenous injection was effective.