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Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.
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Cementos para Huesos , Péptido Relacionado con Gen de Calcitonina , Fosfatos de Calcio , Osteogénesis , Porcinos Enanos , Animales , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Cementos para Huesos/farmacología , Cementos para Huesos/química , Ratones , Porcinos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Columna Vertebral/cirugía , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Línea Celular , Magnesio/farmacología , Magnesio/químicaRESUMEN
Molecular junctions offer significant potential for enhancing thermoelectric power generation. Quantum interference effects and associated sharp features in electron transmission are expected to enable the tuning and enhancement of thermoelectric properties in molecular junctions. To systematically explore the effect of quantum interferences, we designed and synthesized two new classes of porphyrins, P1 and P2, with two methylthio anchoring groups in the 2,13- and 2,12-positions, respectively, and their Zn complexes, Zn-P1 and Zn-P2. Past theory suggests that P1 and Zn-P1 feature destructive quantum interference in single-molecule junctions with gold electrodes and may thus show high thermopower, while P2 and Zn-P2 do not. Our detailed experimental single-molecule break-junction studies of conductance and thermopower, the latter being the first ever performed on porphyrin molecular junctions, revealed that the electrical conductance of the P1 and Zn-P1 junctions is relatively close, and the same holds for P2 and Zn-P2, while there is a 6 times reduction in the electrical conductance between P1 and P2 type junctions. Further, we observed that the thermopower of P1 junctions is slightly larger than for P2 junctions, while Zn-P1 junctions show the largest thermopower and Zn-P2 junctions show the lowest. We relate the experimental results to quantum transport theory using first-principles approaches. While the conductance of P1 and Zn-P1 junctions is robustly predicted to be larger than those of P2 and Zn-P2, computed thermopowers depend sensitively on the level of theory and the single-molecule junction geometry. However, the predicted large difference in conductance and thermopower values between Zn-P1 and Zn-P2 derivatives, suggested in previous model calculations, is not supported by our experimental and theoretical findings.
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Calcium phosphate cement (CPC) has been widely studied, but its lack of osteoinductivity and inadequate mechanical properties limit its application, while strontium is able to promote bone formation and inhibit bone resorption. In this study, different proportions of tristrontium silicate were introduced to create a novel strontium-modified calcium phosphate cement (SMPC). The physicochemical properties of SMPC and CPC were compared, and the microstructures of the bone cements were characterized with scanning electron microscopy assays. Then, the effect of SMPC on cell proliferation and differentiation was examined. Furthermore, local inflammatory response and osteogenesis after SMPC implantation were also confirmed in the study. Finally, a rat model of isolated vertebral defects was used to test the biomechanical properties of the cements. The results showed that SMPC has better injectability and a shorter setting time than CPC. Meanwhile, the addition of tristrontium silicate promoted the mechanical strength of calcium phosphate cement, and the compressive strength of 5% SMPC increased to 6.00 ± 0.74 MPa. However, this promotion effect gradually diminished with an increase in tristrontium silicate, which was also found in the rat model of isolated vertebral defects. Furthermore, SMPC showed a more preferential role in promoting cell proliferation and differentiation compared to CPC. Neither SMPC nor CPC showed significant inflammatory responses in vivo. Histological staining suggested that SMPCs were significantly better than CPC in promoting new bone regeneration. Importantly, this osteogenesis effect of SMPC was positively correlated with the ratio of tristrontium silicate. In conclusion, 5% SMPC is a promising substitute material for bone repair with excellent physicochemical properties and biological activity.
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Cementos para Huesos , Calcio , Animales , Ratas , Cementos para Huesos/farmacología , Cementos para Huesos/química , Fosfatos de Calcio/química , Osteogénesis , Calcio de la Dieta , Silicatos , Estroncio/farmacología , Estroncio/químicaRESUMEN
Molecular junctions offer unique opportunities for controlling charge transport on the atomic scale and for studying energy conversion. For example, quantum interference effects in molecular junctions have been proposed as an avenue for highly efficient thermoelectric power conversion at room temperature. Toward this goal, we investigated the effect of quantum interference on the thermoelectric properties of molecular junctions. Specifically, we employed oligo(phenylene ethynylene) (OPE) derivatives with a para-connected central phenyl ring ( para-OPE3) and meta-connected central ring ( meta-OPE3), which both covalently bind to gold via sulfur anchoring atoms located at their ends. In agreement with predictions from ab initio modeling, our experiments on both single molecules and monolayers show that meta-OPE3 junctions, which are expected to exhibit destructive interference effects, yield a higher thermopower (with â¼20 µV/K) compared with para-OPE3 (with â¼10 µV/K). Our results show that quantum interference effects can indeed be employed to enhance the thermoelectric properties of molecular junctions.
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The present study investigating the variation in plant diversity in Taitemar Lake before and after ecological water transfer is critical for the restoration of the ecological environment of the lower Tarim River. A comprehensive study of the vegetation in Taitemar Lake from 2000 to 2017 was conducted, to determine differences between the overflow and the non-overflow areas, which were monitored along belt transects. There are some conclusions: (1) the ecological benefits of Taitemar Lake gradually emerged with increased water transfer: in the overflow area, the number of species per unit area, vegetation cover, and vegetation density were 6.8 species per 100 m2, 30%, and 1350 per 100 m2, respectively, while the three indices above in the non-overflow area were 1.7 species per 100 m2, 7.0%, and 27.0 per 100 m2, respectively. (2) In recent decades, the major changes in Taitemar Lake were as follows: in the early stage of water transport (2000-2006), the surface vegetation was dominated by newly germinated annual herbs (important value (IV) 0.50), followed by perennial herbs (IV 0.20), and finally shrubs (IV 0.10). After a few years, in 2008, the annual herbs almost disappeared in the overflow are and were replaced by shrubs and perennial herbs. Shrubs were the newly germinating seedlings of native species, and perennial herbs were dominated by Phragmites australis. From 2012 to 2016, under the abundant water conditions, the dominant species composition tended to be simple and the local vegetation developed in the direction of a saline meadow. (3) From 2011 to 2017, P. australis became the dominant species on the shoreline with the Simpson and Shannon indices remaining at low levels.
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Biodiversidad , Monitoreo del Ambiente , Lagos/análisis , Plantas , Movimientos del Agua , Restauración y Remediación Ambiental , Desarrollo de la Planta , Plantas/clasificación , Ríos , Abastecimiento de AguaRESUMEN
Two-photon-regulated, shape-changing DNA nanostructures are demonstrated by integrating a DNA nanotube with a two-photon photocleavable module that enables the opening of the cavities of tube, and becomes partially single-stranded in response to two-photon excitation under 800 nm fs laser pulses.
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ADN/química , Nanotubos/efectos de la radiación , Fotones , Polimerizacion , ADN/efectos de la radiación , Células HeLa , Humanos , Microscopía Confocal , Microscopía Fluorescente , Nanotubos/química , Conformación de Ácido Nucleico/efectos de la radiación , Polimerizacion/efectos de la radiación , Espectroscopía Infrarroja CortaRESUMEN
Quantum interference (QI) can strongly affect electric and thermoelectric properties of molecular junctions (MJs). So far, however, a limited number of experimental studies have explored the influence of QI on thermoelectric transport in MJs. To address this open point, we synthesized derivatives of meta-OPE3 with an electron-withdrawing nitro (-NO2) substituent or an electron-donating N,N-dimethyl amine (-NMe2) substituent, attached at two different positions of the central phenylene ring, and systematically studied the electrical conductance and thermopower of the corresponding gold-molecule-gold junctions. We show that (i) the electrical conductance of MJs depends weakly on the polarity of the substituents but strongly on the substitution position and (ii) MJs with the N,N-dimethyl amine group feature a higher thermopower than MJs with the nitro group. We also present calculations based on first principles, which explain these trends and show that the transport properties are highly sensitive to microscopic details in junctions, exhibiting destructive QI features.
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The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.
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Encéfalo , Hidrogeles , Células Madre Pluripotentes Inducidas , Organoides , Médula Espinal , Organoides/efectos de los fármacos , Organoides/citología , Organoides/metabolismo , Humanos , Animales , Médula Espinal/citología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Encéfalo/metabolismo , Ratas , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacología , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Laminina/farmacología , Laminina/química , Proteoglicanos/química , Ratas Sprague-Dawley , Combinación de Medicamentos , ColágenoRESUMEN
Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.
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Diferenciación Celular , Matriz Extracelular Descelularizada , Hidrogeles , Células Madre Pluripotentes Inducidas , Organoides , Placenta , Médula Espinal , Humanos , Organoides/citología , Organoides/metabolismo , Organoides/efectos de los fármacos , Femenino , Placenta/citología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Embarazo , Hidrogeles/química , Hidrogeles/farmacología , Médula Espinal/citología , Médula Espinal/metabolismo , Diferenciación Celular/efectos de los fármacos , Matriz Extracelular Descelularizada/farmacología , Matriz Extracelular Descelularizada/química , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Laminina/farmacología , Laminina/químicaRESUMEN
This paper is based on long-term monitoring data for soil water, salt content, and groundwater characteristics taken from shelterbelts where there has been no irrigation for at least 5 years. This study investigated the distribution characteristics of soil water and salt content in soils with different textures. The relationships between soil moisture, soil salinity, and groundwater level were analyzed using 3 years of monitoring data from a typical oasis located in an extremely arid area in northwest China. The results showed that (1) the variation trend in soil moisture with soil depth in the shelterbelts varied depending on soil texture. The soil moisture was lower in sandy and loamy shelterbelts and higher in clay shelterbelts. (2) Salinity was higher (about 3.0 mS cm(-1)) in clay shelterbelts and lower (about 0.8 mS cm(-1)) in sandy shelterbelts. (3) There was a negative correlation between soil moisture in the shelterbelts and groundwater level. Soil moisture decreased gradually as the depth of groundwater table declined. (4) There was a positive correlation between soil salinity in the shelterbelts and the depth of groundwater table. Salinity increased gradually as groundwater levels declined.
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Riego Agrícola , Agua Subterránea/química , Cloruro de Sodio/análisis , Suelo/química , Contaminantes Químicos del Agua/análisis , China , Clima , Monitoreo del Ambiente , Agua Subterránea/análisis , SalinidadRESUMEN
Neural tissue engineering is an essential strategy to repair long-segment peripheral nerve defects. Modification of the nerve conduit is an effective way to improve the local microenvironment of the injury site and facilitate nerve regeneration. However, the concurrent release of multiple growth cues that regulate the activity of Schwann cells and neurons remains a challenge. The present study involved the fabrication of a composite hydrogel, specifically methacrylate-anhydride gelatin-ciliary neurotrophic factor/insulin-like growth factor-1 (GelMA-CNTF/IGF-1), with the aim of providing a sustained release of CNTF and IGF-1. The GelMA-CNTF/IGF-1 hydrogels exhibited a swelling rate of 10.2% following a 24 h incubation in vitro. In vitro, GelMA hydrogels demonstrated a high degree of efficiency in the sustained release of CNTF and IGF-1 proteins, with a release rate of 85.9% for CNTF and 90.9% for IGF-1 shown at day 28. In addition, the GelMA-CNTF/IGF-1 composite hydrogel promoted the proliferation of Schwann cells and the production of nerve growth factor (NGF), connective tissue growth factor (CTGF), fibronectin, and laminin and also considerably promoted the axonal growth of neurons. Furthermore, GelMA-CNTF/IGF-1 hydrogels were loaded into PCL electrospun nerve conduits to repair 15 mm sciatic nerve defects in rats. In vivo studies indicated that PCL-GelMA-CNTF/IGF-1 could efficiently accelerate the regeneration of the rat sciatic nerve, promote the formation of the myelin sheath of new axons, promote the electrophysiological function of regenerated nerves, and eventually improve the recovery of motor function in rats. Overall, the PCL-GelMA-CNTF/IGF-1 scaffold presents an attractive new approach for generating an optimal therapeutic alternative for peripheral nerve restoration.
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Factor Neurotrófico Ciliar , Factor I del Crecimiento Similar a la Insulina , Ratas , Animales , Factor Neurotrófico Ciliar/farmacología , Factor Neurotrófico Ciliar/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/farmacología , Ratas Sprague-Dawley , Preparaciones de Acción Retardada/farmacología , Nervio Ciático/lesiones , Nervio Ciático/fisiología , Andamios del Tejido , Regeneración Nerviosa , Hidrogeles/farmacologíaRESUMEN
Modified macroporous structures and active osteogenic substances are necessary to overcome the limited bone regeneration capacity and low degradability of self-curing calcium phosphate cement (CPC). Curcumin (CUR), which possesses strong osteogenic activity and poor aqueous solubility/bioavailability, esterifies the side chains in hyaluronic acid (HA) to form a water-soluble CUR-HA macromolecule. In this study, we incorporated the CUR-HA and glucose microparticles (GMPs) into the CPC powder to fabricate the CUR-HA/GMP/CPC composite, which not only retained the good injectability and mechanical strength of bone cements, but also significantly increased the cement porosity and sustained release property of CUR-HA in vitro. CUR-HA incorporation greatly improved the differentiation ability of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts by activating the RUNX family transcription factor 2/fibroblast growth factor 18 (RUNX2/FGF18) signaling pathway, increasing the expression of osteocalcin and enhancing the alkaline phosphatase activity. In addition, in vivo implantation of CUR-HA/GMP/CPC into femoral condyle defects dramatically accelerated the degradation rate of cement and boosted local vascularization and osteopontin protein expression, and consequently promoted rapid bone regeneration. Therefore, macroporous CPC based composite cement with CUR-HA shows a remarkable ability to repair bone defects and is a promising translational application of modified CPC in clinical practice.
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Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.
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Hidrogeles , Traumatismos de la Médula Espinal , Ratas , Animales , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Factor de Crecimiento Derivado de Plaquetas/farmacología , Factor de Crecimiento Derivado de Plaquetas/uso terapéutico , Diferenciación Celular , Microesferas , Estudios Prospectivos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Péptidos/farmacología , Médula Espinal/patologíaRESUMEN
Dust storms have already become the most serious environmental problem on the south edge of the Taklimakan desert because of their frequent occurrences. To investigate the health effects of dust storms on public health in Moyu County, one of the most severe dust-storm-affected areas located at the south edge of the Taklimakan desert, China, primary data were collected from 1200 respondents by using a questionnaire survey for 15 health symptoms. The data were analyzed by comparing the mean tool (independent t-test and ANOVA) and the severity of different symptoms among different age groups. Principal component analysis (PCA) was applied to further analyze the multivariate relationships between meteorological factors, dust storm intensity, air pollution level, and severity degree of the different symptoms. The results show that significant correlations exist between dust storm intensity, air pollutants (PM2.5, PM10, O3, SO2, NO2, and CO), meteorological factors, and health symptoms. During dusty weather, no matter the age group, the number of respondents who suffered from different health symptoms was higher compared to non-dusty days. Three types of dusty days were considered in this study: suspended dust, blowing dust, and sand storms. The impacts of sand storm weather on public health are stronger than those from blowing dust weather, suspended dust weather (haze), and non-dust weather. The people in the age groups above 60 years and below 15 years were more sensitive to different dust weather than people in the age groups between 15 and 60. "Dry throat with bitter taste", "Depression", "Dry and itchy throat", and "Mouth ulcer" are the main symptoms caused by dust storms.
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Contaminantes Atmosféricos , Arena , Contaminantes Atmosféricos/análisis , China/epidemiología , Polvo/análisis , Monitoreo del Ambiente/métodos , Humanos , Persona de Mediana Edad , Material Particulado/análisis , Encuestas y CuestionariosRESUMEN
Through the improvement of supporting structure and the utilization of the interaction between surrounding rock and supporting structure, the synergistic system of energy-absorbing yielding anti-impact supporting structure and surrounding rock is established. The process of energy absorption device, energy-absorbing yielding anti-impact supporting structure and synergistic system under impact is simulated to analyze the properties of them. The following conclusions could be drawn. The deformation and yielding process under compression of energy absorption device is divided into five stages. Compared with the traditional supporting structure, the energy-absorbing yielding anti-impact supporting structure has the reaction force with lower value and smaller fluctuation range before the deformation of the energy absorption device reaches the third ascending section. The synergy between surrounding rock and supporting structure plays an important role in roadway support. Compared with the supporting structure without surrounding rock, the reaction force of the supporting structure in the synergistic system is lower, and a stationary stage is added in the early stage of the reaction force curve.
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A pre folded energy absorbing device, which is the key device of energy absorption anti impact for roadway support, is tested by quasi-static compression and simulated. The energy absorbing device is divided into zones, and the influence of the area on the load displacement curve of the energy absorbing device is studied according to the area. It is found that the error of numerical simulation is within 5%, indicating that the finite element modeling procedure is appropriate for the problem analyzed here. The device crushes following the pre folded origami pattern in a stable progressive. The device was divided into four areas: the upper and lower opening region of the concave surface four corner parts; the other areas of opening regions; the middle fold edge; the surrounding four sides edge. Each area has effect on the first drop stage and the second rise stage of the load displacement curve. The middle fold edge area has an effect on the peak load value of load displacement curve. Four indicators of peak load, average load, load efficiency, and specific energy absorption were generated from the results of numerical simulation. The strength enhancement of corner region can ensure the energy absorbing device with low peak load and high mean crushing load. The other areas of opening regions affect the first descending and second ascending of the curve. The first rising stage bears the load from the middle edge.
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Angiogenesis is a fundamental process underlying the occurrence, growth and metastasis of hepatocellular carcinoma (HCC), a prevalent tumour type with an extremely poor prognosis due to abundant vasculature. However, the underlying mechanism of angiogenesis in HCC remains largely unknown. Herein, we found that sphingosine-1-phosphate receptor 1 (S1PR1) plays an important role in HCC angiogenesis. S1PR1 was found to be selectively and highly expressed in the blood vessels of HCC tissues compared with those of paratumour tissues. Functionally, high expression of S1PR1 in endothelial cells (ECs) promoted angiogenesis and progression of HCC in vitro and in vivo. Mechanistically, proangiogenic factors (S1P, IL-6, VEGFA) in conditioned medium from HCC cells induced the upregulation of S1PR1 in ECs via the phosphorylation of STAT3 at Y705. Further study also revealed that S1PR1 promotes angiogenesis by decreasing ceramide levels via CerS3 downregulation. Interestingly, we demonstrated that S1PR1 downregulates CerS3 by inducing CerS6 translocation into the nucleus to inhibit CerS3 at the transcriptional level in ECs. In addition, we found that a high concentration of Lenvatinib significantly downregulated the expression of S1PR1 and obviously enhanced S1PR1 knockdown-mediated angiogenesis inhibition, indicating that S1PR1 may be a target by which Lenvatinib combats angiogenesis in HCC. Thus, S1PR1 may be an important target for suppressing angiogenesis in HCC, and inhibiting S1PR1 is a promising approach to antitumor therapy in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Ceramidas/metabolismo , Células Endoteliales/metabolismo , Humanos , Neoplasias Hepáticas/patología , Neovascularización Patológica/metabolismo , Transducción de Señal , Receptores de Esfingosina-1-FosfatoRESUMEN
OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.
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Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs. Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment. Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro. However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency. Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results: We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs. The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain. In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin ß1/GSK3ß/ß-catenin signaling pathway. Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation. Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion: The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.
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Células Madre Germinales Adultas , Neurogénesis , Péptidos , Traumatismos de la Médula Espinal , Animales , Ratas , Células Madre Germinales Adultas/metabolismo , Neurogénesis/fisiología , Péptidos/farmacología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
When the rock burst occurs, energy absorption support is an important method to solve the impact failure. To achieve constant resistance performance of energy absorption device, as an important component of the support, the mechanical properties of one kind of prefolded tube is analyzed by quasi-static compression test. The deformation process of compression test is simulated by ABAQUS and plastic strain nephogram of the numerical model are studied. It is found that the main factors affecting the fluctuation of force-displacement curve is the stiffness of concave side wall. The original tube is improved to constant resistance by changing the side wall. The friction coefficient affects the folding order and form of the energy absorbing device. Lifting the concave side wall stiffness can improve the overall stiffness of energy absorption device and slow down the falling section of force-displacement curve. It is always squeezed by adjacent convex side wall in the process of folding, with large plastic deformation. Compared with the original one, the improved prefolded tube designed in this paper can keep the maximum bearing capacity (Pmax), increase the total energy absorption (E), improve the specific energy absorption (SEA), and decrease the variance (S2) of force-displacement curve.