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This paper studies the maximum reliability of multi-hop relay UAVs, in which UAVs provide wireless services for remote users as a coded cooperative relay without an end-to-end direct communication link. In this paper, the analytical expressions of the total power loss and total bit error rate are derived as reliability measures. First, based on the environmental statistical parameters, a LOS probability model is proposed. Then, the problem of minimizing the bit error rate of static and mobile UAVs is studied. The goal is to minimize the total bit error rate by jointly optimizing the height, elevation, power and path loss and introducing the maximum allowable path loss constraints, transmission power allocation constraints, and UAV height and elevation constraints. At the same time, the total path loss is minimized to achieve maximum ground communication coverage. However, the formulated joint optimization problem is nonconvex and generally difficult to solve. Therefore, we decomposed the problem into two subproblems and proposed an effective joint optimization iteration algorithm. Finally, the simulation results are given, and the analysis shows that the optimal height of different reliability measures is slightly different; thus, using the mobility of UAVs can improve the reliability of communication performance.
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Realizing an ultrahigh-equivalent aperture for space-based direct optical detection using a distributed optical synthetic aperture (DOSA) system with a very low filling ratio is challenging. This study proposes a position-transformation method for DOSA systems with high-frequency domain coverage called High-Frequency domain-Covering discrete Archimedean Spiral Arrays (HFCASA). The study shows that Golay3 HFCASA with a filling ratio of 0.0675% can greatly improve frequency domain coverage and fulfill the resolution requirements of a 200 m aperture telescope. HFCASA provides the theoretical basis for the future deep-space exploration of DOSA.
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The application of traditional materials with constant thermal conductivity in time-varying thermal environments poses great challenges due to their inability of adjusting thermal conductivity according to different requirements, for which reason materials with adjustable thermal conductivity have attracted much attention. However, certain limitations induced by those materials' low softness or harsh adjustment conditions restrict them from being applied in heat dissipation and heat transfer scenarios. In this study, we report a biomimetic liquid metal-elastomer composited foam with adjustable thermal conductivity (B-LM-ECF). Inspired by the rationale of homeothermic animals regulating the thermal conductivity of their subcutaneous tissue, the prepared material adjusts its thermal conductivity via adjusting the volume proportion of liquid metal within it. The thermal conductivity of B-LM-ECF can be adjusted within the range of 0.11-8.4 W·m-1K-1. The adjustment factor η of B-LM-ECF is 76, which is defined as the ratio of the highest to the lowest thermal conductivity of the material. The material enabling reversible switching for itself from thermal insulation to heat dissipation. The prepared material exhibits 45 KPa of Young's modulus with the maximum fracture tensile rate of 600%, facilitating better covering for thermal management objects. We selected a power lithium battery and a smartphone as specific thermal management objects to demonstrate its practical application in thermal management experiment.
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Biomimética , Calor , Animales , Conductividad Térmica , Metales , ElastómerosRESUMEN
Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by α-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in Fxr-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR.
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Colestasis Intrahepática/tratamiento farmacológico , Receptores Citoplasmáticos y Nucleares/metabolismo , Sirtuina 1/metabolismo , Triterpenos/administración & dosificación , 1-Naftilisotiocianato/efectos adversos , Adulto , Animales , Colestasis Intrahepática/sangre , Colestasis Intrahepática/inducido químicamente , Colestasis Intrahepática/genética , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Metabolómica/métodos , Ratones , Persona de Mediana Edad , Triterpenos Pentacíclicos , Transducción de Señal/efectos de los fármacos , Tioacetamida/efectos adversos , Resultado del Tratamiento , Triterpenos/farmacologíaRESUMEN
BACKGROUND: Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined. OBJECTIVE: This study aimed to evaluate prognostic value of different types and distribution of TAMs in CRC. METHODS: Total 27 studies with 6115 patients were searched from PubMed and Embase and analyzed to determine the association between TAMs, including distinct TAM subsets and infiltration location, and CRC survival. The prognostic impact of TAMs on CRC was further stratified by tumor type and mismatch repair system (MMR) status. RESULTS: A pooled analysis indicated that high density of TAMs in CRC tissue was significantly associated with favorable 5-year overall survival (OS) but not with disease-free survival (DFS). CD 68+ TAM subset correlated with better 5-year OS, while neither CD68+NOS2+ M1 subset nor CD163+ M2 subset was correlated with 5-year OS. Increased CD68+ TAM infiltration in tumor stroma but not in tumor islet predicted improved 5-year OS. Stratification by tumor type and MMR status showed that in colon cancer or MMR-proficient CRC, elevated TAM density was associated with better 5-year OS. CONCLUSIONS: High infiltration of CD68+ TAMs could be a favorable prognostic marker in CRC. Future therapies stimulating CD68+ TAM infiltration may be promising in CRC treatment.
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Neoplasias del Colon , Macrófagos Asociados a Tumores , Antígenos de Diferenciación Mielomonocítica , Humanos , Macrófagos , Pronóstico , Microambiente TumoralRESUMEN
BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our ï¬ndings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.
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Células Asesinas Naturales/metabolismo , Macrófagos del Hígado/metabolismo , Cirrosis Hepática Biliar/metabolismo , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Células Asesinas Naturales/patología , Macrófagos del Hígado/patología , Cirrosis Hepática Biliar/fisiopatología , Ratones , Ratones Endogámicos C57BL , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Proteínas Asociadas a Matriz Nuclear/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismoRESUMEN
Electronic skin with high sensitivity, rapid response, and long-term stability has great value in robotics, biomedicine, and in other fields. However, electronic skin still has challenges in terms of sensitivity and response time. In order to solve this problem, flexible electronic skin with high sensitivity and the fast response was proposed, based on piezoresistive graphene films. The electronic skin was a pressure sensor array, composed of a 4 × 4 tactile sensing unit. Each sensing unit contained three layers: The underlying substrate (polyimide substrate), the middle layer (graphene/polyethylene terephthalate film), and the upper substrate bump (polydimethylsiloxane). The results of the measurement and analysis experiments, designed in this paper, indicated that the flexible electronic skin achieved a positive resistance characteristic in the range of 0 kPaâ»600 kPa, a sensitivity of 10.80 Ω /kPa in the range of 0 kPaâ»4 kPa, a loading response time of 10 ms, and a spatial resolution of 5 mm. In addition, the electronic skin realized shape detection on a regular-shaped object, based on the change in the resistance value of each unit. The high sensitivity flexible electronic skin designed in this paper has important application prospects in medical diagnosis, artificial intelligence, and other fields.
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When flight vehicles (e.g., aerospace vehicles, Low Earth Orbit (LEO) satellites, near-space aircrafts, Unmanned Aerial Vehicles (UAVs) and drones) fly at high speed, their surfaces suffer the micro-pressure from high-altitude thin air. The long-term effect of this pressure causes the surface components of flight vehicle to deform or fall off, which can lead to a serious accident. To solve this problem, this paper proposes a sensitivity-compensated micro-pressure flexible sensor based on hyper-elastic plastic material and plate parallel capacitance. The sensor is able to measure a range of 0â»6 kPa micro-pressure suffered by the flight vehicle's surface with high sensitivity and flexible devices. In this paper, we propose the principle, structure design and fabrication of the sensitivity-compensated micro-pressure flexible sensor. We carried out experiments to obtain the static characteristic curve between micro-pressure and the output capacitance of the sensor devices, and investigated the relationship between sensitivity and geometric parameters. We also compared the performance of the flexible sensor before and after sensitivity compensation. The result shows that the sensor can measure a range of 0â»2 kPa and 2â»6 kPa with a sensitivity of 0.27 kPa-1 and 0.021 kPa-1, which are 80% and 141.38% higher than the sensor before compensation; a linearity of 1.39% and 2.88%, which are 51.7% and 13.1% higher than the sensor before compensation; and a hysteresis and repeatability of 4.95% and 2.38%, respectively. The sensor has potential applications in flight vehicles to measure the micro-pressure with high sensitivity and flexibility.
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Model training is a key technique for radar target recognition. Traditional model training algorithms in the framework of single task leaning ignore the relationships among multiple tasks, which degrades the recognition performance. In this paper, we propose a clustered multi-task learning, which can reveal and share the multi-task relationships for radar target recognition. To further make full use of these relationships, the latent multi-task relationships in the projection space are taken into consideration. Specifically, a constraint term in the projection space is proposed, the main idea of which is that multiple tasks within a close cluster should be close to each other in the projection space. In the proposed method, the cluster structures and multi-task relationships can be autonomously learned and utilized in both of the original and projected space. In view of the nonlinear characteristics of radar targets, the proposed method is extended to a non-linear kernel version and the corresponding non-linear multi-task solving method is proposed. Comprehensive experimental studies on simulated high-resolution range profile dataset and MSTAR SAR public database verify the superiority of the proposed method to some related algorithms.
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There are some evidences that pituitary tumors may be sensitive to the anti-proliferative effects of mammalian target of rapamycin (mTOR) inhibitors, while the mechanism and effects remains unclear, it is necessary to find if a specific mTOR inhibition, including the blocking of both mTOR function and expression, generate any effects on pituitary adenoma cells. The object of this study was to examine if specific inhibition of mTOR induced anti-proliferative effect and decreased the GH and PRL hormones secretion in GH3 and MtT/E pituitary adenoma cells by using a kind of mTOR shRNA lentiviral vector. The in vitro experiments results showed mTOR shRNA transfection robustly reduced the GH3 and MtT/E cells viability in all durations (1-6 days) we performed, also specifically decreased both GH and PRL hormones external secretion in GH3 cells. Further results suggested that specific inhibition of mTOR decreased the hormones secretion through anti-proliferation effects on GH3 cells and reducing the hormones synthesis, but not through affecting the process of hormones secretion. Then we used phosphatidic acid (PA), a kind of mTOR activator, to promote the cell proliferation and GH and PRL hormones secretion in GH3 cells while the effects were blocked by mTOR shRNA transfection. In addition, we examined in vitro effects of PA treatment and mTOR shRNA gene transfection on major proteins expressed in the mTOR pathway in GH3 cells, and confirmed that PA treatment significant increased the protein levels of pmTOR, pS6 K and p4EBP1 in the scramble shRNA group, while the increase of protein levels was blocked by mTOR shRNA gene transfection. Moreover, mTOR shRNA gene transfection definitely inhibited the expression of mTOR and reduced the expression of pmTOR, pS6K and p4EBP1 in either PA or no PA treatment groups. These findings indicated that specific inhibition of mTOR pathway induced anti-proliferative effect and decreased the GH and PRL hormones secretion in cultured pituitary adenoma cells, which may be a novel promising and potential treatment modality for patients with secreting or non-secreting pituitary adenomas.
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Proliferación Celular/fisiología , Hormona del Crecimiento/metabolismo , Prolactina/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Análisis de Varianza , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Ensayo de Inmunoadsorción Enzimática , Humanos , Ácidos Fosfatidicos/farmacología , Neoplasias Hipofisarias/patología , ARN Interferente Pequeño/genética , Ratas , Proteínas Quinasas S6 Ribosómicas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/genética , Factores de Tiempo , TransfecciónRESUMEN
Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.
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Bancos de Muestras Biológicas/normas , Investigación Biomédica/normas , Glioma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China , Bases de Datos Factuales/normas , Femenino , Glioma/cirugía , Humanos , Lactante , Masculino , Persona de Mediana Edad , Manejo de Especímenes , Investigación Biomédica Traslacional/normas , Adulto JovenRESUMEN
OBJECTIVE: To compare frequencies of natural killer (NK) cell subsets and their surface expression of the NKG2D receptor in patients with primary biliary cirrhosis (PBC), and to determine the correlation between expression of MICA on monocytes and function-associated receptors on the NK cells of PBC patients. METHODS: Twenty patients with PBC and 18 healthy donors were included in the study. Peripheral blood samples anticoagulated with heparin were labeled with the following antibody combinations: anti-CD45/anti-CD14/anti-MICA, antiCD3/anti-CD56/anti-CD16/anti-NKG2D. Frequencies of MICA-positive monocytes, NK cell subsets, and NK cells with surface expression of NKG2D were measured with flow cytometry. Correlation of MICA expression on monocytes with NKG2D expreesion on NK cells was assessed through linear correlation and regression analysis. RESULTS: The PBC patients had significantly lower percentages of NK cells than the healthy donors (6.8%+/-2.9% vs.16.4%+/-3.4%, P =0.000<0.05). In the PBC patients, the percentage of CD56-positive NK ceils was significantly higher than that of CD16-positive NK cells (4.2%+/-2.8% vs.1.4%+/-0.7%, P=0.003<0.05). The PBC patients also had significantly higher percentage of NKG2D surface expressing CD56-positive NK cells than the healthy donors (79.4%+/-10.2% vs.64.8%+/-10.7%, P=0.000<0.05). The PBC patients and healthy donors showed no statistically significant differences in percentages of NKG2D surface expressing CDl6-positive NK (70.1%+/-12.9% vs.61.1%+/-5.9%, P=0.078>0.05). MICA was seldom detected on normal monocytes (2.6%+/-1.9%), but present for 51.6%+/-16.2% of monoeytes from the PBC patients (P =0.000<0.05). There was a significant difference in frequency of CD14/MICA double-positive monocytes between the healthy donors and PBC patients. No correlation of MICA expression on monocytes with NKG2D expression on NK cells was found. CONCLUSION: PBC patients have lower levels of NK cells in peripheral blood than their healthy counterparts. PBC patients also have higher levels of the CD56+ NK cell subset and cells with surface expression of the activated NKG2D receptor. It appears that PBC patients have a greater level of CD14+MICA+ peripheral blood mononuclear cells. NK cells may be affected by the PBC-related monocytes and participate in disease pathogenesis through immune regulation.
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Células Asesinas Naturales , Cirrosis Hepática Biliar , Citometría de Flujo , Humanos , Subfamilia K de Receptores Similares a Lectina de Células NKRESUMEN
BACKGROUND: The ability of preoperative MRI-sequences to predict the consistency of intracranial meningiomas has not yet been clearly defined. We aim to demonstrate that diffusion tensor imaging (DTI) improves the prediction of intracranial meningiomas consistency. METHODS: We prospectively studied 110 meningioma patients operated on in a single center from March 1st to the 25th of May 2012. Demographic data, location and size of the tumor, peritumoral edema, T1WI, T2WI, proton density weighted (PDWI), fluid-attenuated inversion recover (FLAIR) sequences, and arterial spin labeling (ASL) perfusion were studied and compared with the gray matter signal to predict meningioma consistency. Diffusion tensor imaging (DTI) with fractional anisotropy (FA) and mean diffusivity (MD) maps were included in the preoperative MRI. Meningioma consistency was evaluated by the operating surgeon who was unaware of the neuroradiological findings. RESULTS: In univariate analysis, meningioma size (diameter > 2 cm) and supratentorial or sphenoidal wing location were more frequently associated with hard-consistency meningiomas (p < 0.05). In addition, isointense signal on MD maps (p = 0.009), hyperintense signal on FA maps, and FA value > 0.3 (p = 0.00001) were associated with hard-consistency tumors. Age and sex, T1WI, T2WI, PDWI, FLAIR, or ASL perfusion sequences and peritumoral edema were not significantly associated with meningioma consistency. In logistic regression analysis, the most accurate model (AUC: 0.9459) for predicting a hard-consistency meningioma shows that an isointense signal in MD-maps, a hyperintense signal in FA-maps, and an FA value of more than 0.3 have a significant predictive value. CONCLUSIONS: FA value and MD and FA maps are useful for prediction of meningioma consistency and, therefore, may be considered in the preoperative routine MRI examination of all patients with intracranial meningiomas.
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Imagen de Difusión Tensora/métodos , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Neoplasias Meníngeas/clasificación , Neoplasias Meníngeas/patología , Meningioma/clasificación , Meningioma/patología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , PronósticoRESUMEN
The computational complexity of one-dimensional time fractional reaction-diffusion equation is O(N²M) compared with O(NM) for classical integer reaction-diffusion equation. Parallel computing is used to overcome this challenge. Domain decomposition method (DDM) embodies large potential for parallelization of the numerical solution for fractional equations and serves as a basis for distributed, parallel computations. A domain decomposition algorithm for time fractional reaction-diffusion equation with implicit finite difference method is proposed. The domain decomposition algorithm keeps the same parallelism but needs much fewer iterations, compared with Jacobi iteration in each time step. Numerical experiments are used to verify the efficiency of the obtained algorithm.
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Algoritmos , Cómputos Matemáticos , Modelos Teóricos , Reproducibilidad de los ResultadosRESUMEN
It is very time consuming to solve fractional differential equations. The computational complexity of two-dimensional fractional differential equation (2D-TFDE) with iterative implicit finite difference method is O(M(x)M(y)N(2)). In this paper, we present a parallel algorithm for 2D-TFDE and give an in-depth discussion about this algorithm. A task distribution model and data layout with virtual boundary are designed for this parallel algorithm. The experimental results show that the parallel algorithm compares well with the exact solution. The parallel algorithm on single Intel Xeon X5540 CPU runs 3.16-4.17 times faster than the serial algorithm on single CPU core. The parallel efficiency of 81 processes is up to 88.24% compared with 9 processes on a distributed memory cluster system. We do think that the parallel computing technology will become a very basic method for the computational intensive fractional applications in the near future.
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Algoritmos , Difusión , Modelos Teóricos , Análisis Numérico Asistido por Computador , Simulación por ComputadorRESUMEN
Vehicle skin is the key component in maintaining the aerodynamic shape of the vehicle. A deformable high-speed vehicle needs to adjust its shape in real time to realize optimum aerodynamic efficiency and to withstand extreme heat flow induced by high-speed flight, which requires the skin to possess large strain and high-temperature resistance. Traditional vehicle skin cannot satisfy both of the requirements. Biomimetic flexible skin for deformable high-speed vehicles (DHSV-bio-FS) combines flexible material fabrication with transpiration cooling technology, which can simulate human skin sweat cooling, and has the characteristics of large strain and high-temperature resistance. The thermal protection performance of the prepared prototype of DHSV-bio-FS was evaluated by simulation and wind tunnel experiments at 40% tensile strain with liquid water as coolant. Simulation results suggest that the surface temperature of the DHSV-bio-FS at 40% tensile strain is consistent with the temperature of the coolant (350 K) in a 3,000 K high-temperature gas environment. In addition, the prepared prototype DHSV-bio-FS survived for 1,200 s in a high-temperature gas environment of 200 kW/m2 in wind tunnel experiments. This paper verifies the reliability of DHSV-bio-FS in a high-temperature gas environment and can be deployed in applications of flexible skin for deformable high-speed vehicles (DHSV-FS).
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Background and Aims: The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences. Methods: Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system. Results: Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations. Conclusions: Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection.
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Critical-size bone defects are a common and intractable clinical problem that typically requires filling in with surgical implants to facilitate bone regeneration. Considering the limitations of autologous bone and allogeneic bone in clinical applications, such as secondary damage or immunogenicity, injectable microhydrogels with osteogenic and angiogenic effects have received considerable attention. Herein, polydopamine (PDA)-functionalized strontium alginate/nanohydroxyapatite (Sr-Alg/nHA) composite microhydrogels loaded with vascular endothelial growth factor (VEGF) were prepared using microfluidic technology. This composite microhydrogel released strontium ions stably for at least 42 days to promote bone formation. The PDA coating can release VEGF in a controlled manner, effectively promote angiogenesis around bone defects, and provide nutritional support for new bone formation. In in vitro experiments, the composite microhydrogels had good biocompatibility. The PDA coating greatly improves cell adhesion on the composite microhydrogel and provides good controlled release of VEGF. Therefore, this composite microhydrogel effectively promotes osteogenic differentiation and vascularization. In in vivo experiments, composite microhydrogels were injected into critical-size bone defects in the skull of rats, and they were shown by microcomputed tomography and tissue sections to be effective in promoting bone regeneration. These findings demonstrated that this novel microhydrogel effectively promotes bone formation and angiogenesis at the site of bone defects.
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Indoles , Osteogénesis , Polímeros , Factor A de Crecimiento Endotelial Vascular , Ratas , Animales , Factor A de Crecimiento Endotelial Vascular/farmacología , Alginatos/farmacología , Microtomografía por Rayos X , Angiogénesis , Regeneración Ósea , Cráneo , Hidroxiapatitas/farmacología , Estroncio/farmacologíaRESUMEN
The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.
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BACKGROUND: Intelligence is much important for brain tumor patients after their operation, while the reports about surgical related intelligence deficits are not frequent. It is not only theoretically important but also meaningful for clinical practice. METHODS: Wechsler Adult Intelligence Scale was employed to evaluate the intelligence of 103 patients with intracranial tumor and to compare the intelligence quotient (IQ), verbal IQ (VIQ), and performance IQ (PIQ) between the intracerebral and extracerebral subgroups. RESULTS: Although preoperative intelligence deficits appeared in all subgroups, IQ, VIQ, and PIQ were not found to have any significant difference between the intracerebral and extracerebral subgroups, but with VIQ lower than PIQ in all the subgroups. An immediate postoperative follow-up demonstrated a decline of IQ and PIQ in the extracerebral subgroup, but an improvement of VIQ in the right intracerebral subgroup. Pituitary adenoma resection exerted no effect on intelligence. In addition, age, years of education, and tumor size were found to play important roles. CONCLUSIONS: Brain tumors will impair IQ, VIQ, and PIQ. The extracerebral tumor resection can deteriorate IQ and PIQ. However, right intracerebral tumor resection is beneficial to VIQ, and transsphenoidal pituitary adenoma resection performs no effect on intelligence.