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BACKGROUND: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice. METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1). RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy. CONCLUSION: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.
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Apoptosis , Autofagia , Dexmedetomidina , Miocitos Cardíacos , Traumatismos Experimentales por Radiación , Animales , Autofagia/efectos de los fármacos , Autofagia/efectos de la radiación , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/efectos de la radiación , Miocitos Cardíacos/metabolismo , Apoptosis/efectos de los fármacos , Masculino , Dexmedetomidina/farmacología , Traumatismos Experimentales por Radiación/prevención & control , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Protectores contra Radiación/farmacología , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Ratones , Proteínas Relacionadas con la Autofagia/metabolismo , Ratones Endogámicos C57BL , Proteínas Reguladoras de la Apoptosis/metabolismoRESUMEN
Twinning is profuse in bcc transition metals (TMs) except bulk W and Mo. However, W and Mo nanocrystals surprisingly exhibit twinning during room temperature compression, which is completely unexpected as established nucleation mechanisms are not viable in them. Here, we reveal the physical origin of deformation twinning in W and Mo. We employ density functional theory (DFT) and a reduced-constraint slip method to compute the stress-dependent generalized stacking fault enthalpy (GSFH), the thermodynamic quantity to be minimized under constant loading. The simple slipped structures and GSFH lines show that compressive stresses stabilize a two-layer twin embryo, which can grow rapidly via twinning disconnections with negligible energy barriers. Direct atomistic simulations unveil the explicit twinning path in agreement with the DFT GSFH lines. Twinning is thus the preferred deformation mechanism in W and Mo when shear stresses are coupled with high compressive stresses. Furthermore, twinnability can be related to the elastic constants of a stacking fault phase (SFP). The hcp phase may serve as a candidate SFP for the {112}⟨1[over ¯]1[over ¯]1⟩ twinning system in bcc TMs and alloys, which is coincident with the {111}⟨112[over ¯]⟩ twinning in fcc structures.
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Trajectory prediction is an essential task in many applications, including autonomous driving, robotics, and surveillance systems. In this paper, we propose a novel trajectory prediction network, called TFBNet (trajectory feature-boosting network), that utilizes trajectory feature boosting to enhance prediction accuracy. TFBNet operates by mapping the original trajectory data to a high-dimensional space, analyzing the change rules of the trajectory in this space, and finally aggregating the trajectory goals to generate the final trajectory. Our approach presents a new perspective on trajectory prediction. We evaluate TFBNet on five real-world datasets and compare it to state-of-the-art methods. Our results demonstrate that TFBNet achieves significant improvements in the ADE (average displacement error) and FDE (final displacement error) indicators, with increases of 46% and 52%, respectively. These results validate the effectiveness of our proposed approach and its potential to improve the performance of trajectory prediction models in various applications.
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Stress graphitization is a unique phenomenon at the carbon nanotube (CNT)-matrix interfaces in CNT/carbon matrix (CNT/C) composites. A lack of fundamental atomistic understanding of its evolution mechanisms and a gap between the theoretical and experimental research have hindered the pursuit of utilizing this phenomenon for producing ultrahigh-performance CNT/C composites. Here, we performed reactive molecular dynamics simulations along with an experimental study to explore stress graphitization mechanisms of a CNT/polyacrylonitrile (PAN)-based carbon matrix composite. Different CNT contents in the composite were considered, while the nanotube alignment was controlled in one direction in the simulations. We observe that the system with a higher CNT content exhibits higher localized stress concentration in the periphery of CNTs, causing alignment of the nitrile groups in the PAN matrix along the CNTs, which subsequently results in preferential dehydrogenation and clustering of carbon rings and eventually graphitization of the PAN matrix when carbonized at 1500 K. These simulation results have been validated by experimentally produced CNT/PAN-based carbon matrix composite films, with transmission electron microscopy images showing the formation of additional graphitic layers converted by the PAN matrix around CNTs, where 82 and 144% improvements of the tensile strength and Young's modulus are achieved, respectively. The presented atomistic details of stress graphitization can provide guidance for further optimizing CNT-matrix interfaces in a more predictive and controllable way for the development of novel CNT/C composites with high performance.
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Renal tubule chips have emerged as a promising platform for drug nephrotoxicity testing. However, the reported renal tubule chips hardly replicate the unique structure of renal tubules with thick proximal and distal tubules and a thin loop of Henle. In this study, we developed a fully structured scaffold-free vascularized renal tubule on a microfluidic chip. On the chip, the renal epithelial cell-laden hollow calcium-polymerized alginate tube with thick segments at both ends and a thin middle segment was U-shaped embedded in collagen hydrogel, parallel to the endothelial cell-laden hollow calcium-polymerized alginate tube with uniform tube diameter. After the alginate tubes were on-chip degraded, the renal epithelial cells and endothelial cells automatically attached to the collagen hydrogel and proliferated to form the renal tubule with proximal tubule, loop of Henle and distal tubule as well as peritubular blood vessel. We evaluated the viability of cells on the hollow alginate tubes, characterized the distribution and morphology of cells before and after the degradation of the alginate tube, and confirmed the proliferation of cells and the metabolic function of cells in terms of ATP synthesis, fibronectin secretion and VEGFR2 expression on the chip. The enhanced metabolic functions of renal epithelial cells and endothelial cells were preliminarily demonstrated. This study provides new insights into designing a more biomimetic renal tubule on a microfluidic chip.
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Calcio , Células Endoteliales , Colágeno , Hidrogeles , AlginatosRESUMEN
Ropivacaine, a common local anesthetic in the clinic, has anti-proliferative and pro-apoptotic effects in numerous cancers, however, the underlying regulatory mechanism of ropivacaine in hepatocellular carcinoma remains unclear. In the current study, human HepG2 cells were stimulated with different ropivacaine concentrations. Cell Counting Kit-8 assay, cell colony formation, and cell cycle were used to monitor cell viability. Cell apoptosis, migration, and invasion were determined by flow cytometry and transwell assays. Tumor xenograft experiments were performed to prove the anti-cancer effect of ropivacaine in vivo. A high dose of ropivacaine inhibited proliferation and promoted apoptosis of HepG2 cells in a dose-dependent manner. Ropivacaine challenge also arrested cells in the G2 phase, followed by a decline in the protein expression of cyclin D1 and cyclin-dependent kinase 2, and an increase in p27 levels in HepG2 cells. Additionally, different ropivacaine doses suppressed cell migration and invasion by upregulating E-cadherin expression and downregulating N-cadherin expression. Mechanically, ropivacaine challenge gradually restrained insulin-like growth factor-1 receptor (IGF-1 R) expression and the activities of phosphorylated-PI3K, AKT, and mTOR in HepG2 cells with increased ropivacaine doses. In the tumor xenograft experiment, ropivacaine was confirmed to inhibit tumor growth, accompanied by inhibition of the IGF-1 R/PI3K/AKT/mTOR signaling axis. In conclusion, ropivacaine suppressed tumor biological characteristics and promoted apoptosis, resulting in the suppression of hepatocellular carcinoma progression by targeting the IGF-1 R/PI3K/AKT/mTOR signaling pathway. It is possible that ropivacaine-mediated local anesthesia may be developed as a novel surgical adjuvant drug for treating hepatocellular carcinoma.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Ropivacaína/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We investigated the microstructures of carbon nanotube (CNT) films and the effect of CNT length on their mechanical performance. 230 µm-, 300 µm-, and 360 µm- long CNTs were grown and used to fabricate CNT films by a winding process. Opposite from the length effect on CNT fibers, it has been found that the mechanical properties of the CNT films decrease with increasing CNT length. Without fiber twisting, short CNTs tend to bundle together tightly by themselves in the film structure, resulting in an enhanced packing density; meanwhile, they also provide a high degree of CNT alignment, which prominently contributes to high mechanical properties of the CNT films. When CNTs are long, they tend to be bent and entangled, which significantly reduce their packing density, impairing the film mechanical behaviors severely. It has also been unveiled that the determinant effect of the CNT alignment on the film mechanical properties is more significant than that of the film packing density. These findings provide guidance on the optimal CNT length when attempting to fabricate high-performance macroscopic CNT assemblies.
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The surface nano-crystallization of Ni2FeCoMo0.5V0.2 medium-entropy alloy was realized by rotationally accelerated shot peening (RASP). The average grain size at the surface layer is ~37 nm, and the nano-grained layer is as thin as ~20 µm. Transmission electron microscopy analysis revealed that deformation twinning and dislocation activities are responsible for the effective grain refinement of the high-entropy alloy. In order to reveal the effectiveness of surface nano-crystallization on the Ni2FeCoMo0.5V0.2 medium-entropy alloy, a common model material, Ni, is used as a reference. Under the same shot peening condition, the surface layer of Ni could only be refined to an average grain size of ~234 nm. An ultrafine grained surface layer is less effective in absorbing strain energy than a nano-grain layer. Thus, grain refinement could be realized at a depth up to 70 µm in the Ni sample.
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Ultrastrong materials can notably help with improving the energy efficiency of transportation vehicles by reducing their weight. Grain refinement by severe plastic deformation is, so far, the most effective approach to produce bulk strong nanostructured metals, but its scaling up for industrial production has been a challenge. Here, we report an ultrastrong (2.15 GPa) low-carbon nanosteel processed by heterostructure and interstitial mediated warm rolling. The nanosteel consists of thin (~17.8 nm) lamellae, which was enabled by two unreported mechanisms: (i) improving deformation compatibility of dual-phase heterostructure by adjusting warm rolling temperature and (ii) segregating carbon atoms to lamellar boundaries to stabilize the nanolamellae. Defying our intuition, warm rolling produced finer lamellae than cold rolling, which demonstrates the potential and importance of tuning deformation compatibility of interstitial containing heterostructure for nanocrystallization. This previously unreported approach is applicable to most low-carbon, low-alloy steels for producing ultrahigh strength materials in industrial scale.
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Low plasticity has been a major issue for the application of Mg alloys. Here, based on the generalized stacking fault energy curves and Arrhenius equation, we systematically study alloying effects on the stacking fault energies and the activation probability of basal and non-basal ãaã, and pyramidal ãc + aã slip systems in twenty-one Mg alloys. Our results reveal that activation of ãc + aã slip systems on pyramidal II plane can significantly improve the plasticity. For example, Ca is found to promote the activation probability of this slip system by one order of magnitude and dramatically improve the plasticity of Mg.
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Circadian disruption has been implicated in tumour development, but the underlying mechanism remains unclear. Here, we show that the molecular clockwork within malignant human pancreatic epithelium is disrupted and that this disruption is mediated by miR-135b-induced BMAL1 repression. miR-135b directly targets the BMAL1 3'-UTR and thereby disturbs the pancreatic oscillator, and the downregulation of miR-135b is essential for the realignment of the cellular clock. Asynchrony between miR-135b and BMAL1 expression impairs the local circadian gating control of tumour suppression and significantly promotes tumourigenesis and resistance to gemcitabine in pancreatic cancer (PC) cells, as demonstrated by bioinformatics analyses of public PC data sets and in vitro and in vivo functional studies. Moreover, we found that YY1 transcriptionally activated miR-135b and formed a 'miR-135b-BMAL1-YY1' loop, which holds significant predictive and prognostic value for patients with PC. Thus, our work has identified a novel signalling loop that mediates pancreatic clock disruption as an important mechanism of PC progression and chemoresistance.
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Factores de Transcripción ARNTL/metabolismo , Relojes Biológicos , Carcinogénesis/genética , Resistencia a Antineoplásicos/genética , MicroARNs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Factor de Transcripción YY1/metabolismo , Animales , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Células Epiteliales/metabolismo , Células Epiteliales/patología , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Conductos Pancreáticos/metabolismo , Conductos Pancreáticos/patología , PronósticoRESUMEN
Carbon nanotube (CNT) fiber has not shown its advantage as next-generation light-weight conductor due to the large contact resistance between CNTs, as reflected by its low conductivity and ampacity. Coating CNT fiber with a metal layer like Cu has become an effective solution to this problem. However, the weak CNT-Cu interfacial bonding significantly limits the mechanical and electrical performances. Here, we report that a strong CNT-Cu interface can be formed by introducing a Ni nanobuffer layer before depositing the Cu layer. The Ni nanobuffer layer remarkably promotes the load and heat transfer efficiencies between the CNT fiber and Cu layer and improves the quality of the deposited Cu layer. As a result, the new composite fiber with a 2 µm thick Cu layer can exhibit a superhigh effective strength >800 MPa, electrical conductivity >2 × 107 S/m, and ampacity >1 × 105 A/cm2. The composite fiber can also sustain 10 000 times of bending and continuously work for 100 h at 90% ampacity.
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In this study, a kind of Al-TiB2/TiC in situ composite was successfully prepared using the melt reaction method and the accumulative roll-bonding (ARB) technique. The microstructure evolution of the composites with different deformation treatments was characterized using field emission scanning electron microscopy (FESEM) and a transmission electron microscope (TEM). The mechanical properties of the Al-TiB2/TiC in situ composite were also studied with tensile and microhardness tests. It was found that the distribution of reinforcement particles becomes more homogenous with an increasing ARB cycle. Meanwhile, the mechanical properties showed great improvement during the ARB process. The ultimate tensile strength (UTS) and microhardness of the composites were increased to 173.1 MPa and 63.3 Hv after two ARB cycles, respectively. Furthermore, the strengthening mechanism of the composite was analyzed based on its fracture morphologies.
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High-carbon martensite steels (with C > 0.5 wt.%) are very hard but at the same time as brittle as glass in as-quenched or low-temperature-tempered state. Such extreme brittleness, originating from a twin microstructure, has rendered these steels almost useless in martensite state. Therefore, for more than a century it has been a common knowledge that high-carbon martensitic steels are intrinsically brittle and thus are not expected to find any application in harsh loading conditions. Here we report that these brittle steels can be transformed into super-strong ones exhibiting a combination of ultrahigh strength and significant toughness, through a simple grain-refinement treatment, which refines the grain size to ~4 µm. As a result, an ultra-high tensile strength of 2.4~2.6 GPa, a significant elongation of 4~10% and a good fracture toughness (K1C) of 23.5~29.6 MPa m1/2 were obtained in high-carbon martensitic steels with 0.61-0.65 wt.% C. These properties are comparable with those of "the king of super-high-strength steels"-maraging steels, but achieved at merely 1/30~1/50 of the price. The drastic enhancement in mechanical properties is found to arise from a transition from the conventional twin microstructure to a dislocation one by grain refinement. Our finding may provide a new route to manufacturing super-strong steels in a simple and economic way.
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Nanostructured (NS) and ultrafine-grained (UFG) materials have high strength and relatively low ductility. Their toughness has not been comprehensively investigated. Here we report the Charpy impact behavior and the corresponding microstructural evolutions in UFG Cu with equi-axed and elongated grains which were prepared by equal channel angular pressing (ECAP) for 2 and 16 passes at room temperature. It is found that their impact toughness (48 J/cm2) is almost comparable to that of coarse grained (CG) Cu: 55 J/cm2. The high strain rate during the Charpy impact was found to enhance the strain hardening capability of the UFG Cu due to the suppression of dynamic dislocation recovery. The crack in the CG Cu was blunted by dislocation-slip mediated plastic deformation, while the cracks in the UFG Cu were formed at grain boundaries and triple junctions due to their limited plasticity. Near the crack surfaces the elongated grains in ECAP-2 sample were refined by recrystallization, while equi-axed grains in the ECAP-16 sample grew larger.
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It has been more than a decade since the thermal conductivity of vertically aligned carbon nanotube (VACNT) arrays was reported possible to exceed that of the best thermal greases or phase change materials by an order of magnitude. Despite tremendous prospects as a thermal interface material (TIM), results were discouraging for practical applications. The primary reason is the large thermal contact resistance between the CNT tips and the heat sink. Here we report a simultaneous sevenfold increase in in-plane thermal conductivity and a fourfold reduction in the thermal contact resistance at the flexible CNT-SiO2 coated heat sink interface by coupling the CNTs with orderly physical overlapping along the horizontal direction through an engineering approach (shear pressing). The removal of empty space rapidly increases the density of transport channels, and the replacement of the fine CNT tips with their cylindrical surface insures intimate contact at CNT-SiO2 interface. Our results suggest horizontally aligned CNT arrays exhibit remarkably enhanced in-plane thermal conductivity and reduced out-of-plane thermal conductivity and thermal contact resistance. This novel structure makes CNT film promising for applications in chip-level heat dissipation. Besides TIM, it also provides for a solution to anisotropic heat spreader which is significant for eliminating hot spots.
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Al(1060)/Mg(AZ31)/Al(1060) multilayered composite was successfully produced using an accumulative roll bonding (ARB) process for up to four cycles at an elevated temperature (400 °C). The microstructure evolution of the composites and the bonding characteristics at the interfaces between Al and Mg layers with increasing ARB cycles were characterized through optical microscopy, field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). It was found that the grains of Al and Mg layers were significantly refined and Al3Mg2 and Al12 Mg17 intermetallic compound layers formed at the Al/Mg bonding interfaces. The strength increased gradually and the ultimate tensile strength (UTS) reached a maximum value of about 240 MPa at the third pass. Furthermore, the strengthening mechanism of the composite was analyzed based on the fracture morphologies.
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Scanning electron microscopy transmission Kikuchi diffraction is able to identify twins in nanocrystalline material, regardless of their crystallographic orientation. In this study, it was employed to characterize deformation twins in Cu/10 wt % Zn processed by high-pressure torsion. It was found that in 83% of grains containing twins, at least one twin intersects with a triple junction. This suggests that triple junctions could have promoted the nucleation of deformation twins. It should be cautioned that this technique might be unable to detect extremely small nanoscale twins thinner than its step size.
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Grain refinement can make conventional metals several times stronger, but this comes at dramatic loss of ductility. Here we report a heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse-grained metal. It also has higher strain hardening than coarse-grained Ti, which was hitherto believed impossible. The heterogeneous lamella structure is characterized with soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The unusual high strength is obtained with the assistance of high back stress developed from heterogeneous yielding, whereas the high ductility is attributed to back-stress hardening and dislocation hardening. The process discovered here is amenable to large-scale industrial production at low cost, and might be applicable to other metal systems.