Dexmedetomidine ameliorates x-ray-induced myocardial injury via alleviating cardiomyocyte apoptosis and autophagy.

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.

Origin of Deformation Twinning in bcc Tungsten and Molybdenum.

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.

On-chip construction of a fully structured scaffold-free vascularized renal tubule.

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.

A Novel Trajectory Feature-Boosting Network for Trajectory Prediction.

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.

Length-dependent carbon nanotube film structures and mechanical properties.

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.

Effective Surface Nano-Crystallization of Ni2FeCoMo0.5V0.2 Medium Entropy Alloy by Rotationally Accelerated Shot Peening (RASP).

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.

Heterogeneous lamella structure unites ultrafine-grain strength with coarse-grain ductility.

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.

Extraordinary strain hardening by gradient structure.

Gradient structures have evolved over millions of years through natural selection and optimization in many biological systems such as bones and plant stems, where the structures change gradually from the surface to interior. The advantage of gradient structures is their maximization of physical and mechanical performance while minimizing material cost. Here we report that the gradient structure in engineering materials such as metals renders a unique extra strain hardening, which leads to high ductility. The grain-size gradient under uniaxial tension induces a macroscopic strain gradient and converts the applied uniaxial stress to multiaxial stresses due to the evolution of incompatible deformation along the gradient depth. Thereby the accumulation and interaction of dislocations are promoted, resulting in an extra strain hardening and an obvious strain hardening rate up-turn. Such extraordinary strain hardening, which is inherent to gradient structures and does not exist in homogeneous materials, provides a hitherto unknown strategy to develop strong and ductile materials by architecting heterogeneous nanostructures.

Strong and Conductive Dry Carbon Nanotube Films by Microcombing.

In order to maximize the carbon nanotube (CNT) buckypaper properties, it is critical to improve their alignment and reduce their waviness. In this paper, a novel approach, microcombing, is reported to fabricate aligned CNT films with a uniform structure. High level of nanotube alignment and straightness was achieved using sharp surgical blades with microsized features at the blade edges to comb single layer of CNT sheet. These microcombs also reduced structural defects within the film and enhanced the nanotube packing density. Following the microcombing approach, the as-produced CNT films demonstrated a tensile strength of up to 3.2 GPa, Young's modulus of up to 172 GPa, and electrical conductivity of up to 1.8 × 10(5) S m(-1) , which are much superior to previously reported CNT films or buckypapers. More importantly, this novel technique requires less rigorous process control and can construct CNT films with reproducible properties.

[The effect of propofol and sevoflurane on the perioperative immunity in patients under laparoscopic radical resection of colorectal cancer].

OBJECTIVE: To compare the effect of propofol and sevoflurane on perioperative immunity and surgical outcomes in patients undergoing laparoscopic radical resection of colorectal cancer. METHODS: During September 2012 to April 2014 in Sir Run Run Shaw Hospital, thirty patients scheduled for laparoscopic colorectal cancer radical resection were randomly assigned into two groups: propofol TCI anesthesia and sevoflurane inhale anesthesia. Venous blood was taken before induction, on finishing the surgery and 24 h after surgery for lymphocyte subtype study by flow cytometry. Postoperative outcomes including intestinal obstruction, urine retention, anastomotic fistula and incision healing, antibiotic using time, hospital-stay time were compared. RESULTS: In the sevoflurane group, the percentage of CD3⁺, CD4⁺ and CD19⁺ subtype were increased immediately after surgery ((64.0 ± 13.5)%, (37.5 ± 11.8)%, (12.3 ± 4.5)%) comparing to preoperative level ((59.0 ± 12.0)%, (33.0 ± 8.3)%, (9.9 ± 4.3)%) (t= 3.423, 2.543, 2.768 respectively, all P<0.05), while NK cell percentage was significantly decreased ((22.9 ± 13.2)% vs (30.7 ± 11.9)%) (t=-3.444, P<0.01). The changes of CD3⁺, CD19⁺ and NK cell remained significant at 24 h ((63.5 ± 9.3)%, (13.0 ± 4.0)%, (22.5 ± 7.2)%) (t=2.961, 3.502, -4.621 respectively, all P<0.05). In the propofol group, the levels of CD3⁺, CD4⁺, CD19⁺ and CD4⁺ /CD8⁺ ratio were significantly increased after surgery ((69.4 ± 9.7)%, (43.2 ± 9.2)%, (15.2 ± 7.4)%, 1.9 ± 0.9) comparing to the preoperative levels ((61.9 ± 13.6)%, (34.6 ± 8.9)%, (10.4 ± 4.5)%, 1.5 ± 0.7) (t= 4.732, 6.132, 3.688, 4.640 respectively, all P<0.01), and NK cell was significantly decreased ((14.7 ± 10.2)% vs (27.2 ± 14.3)%) (t=-4.935, P<0.01). These changes were similar to that of the sevoflurane group. At 24 h in the propofol group, comparing with those after surgery, CD3⁺, CD4⁺ and CD4⁺ /CD8⁺ ratio were significantly decreased ((63.6 ± 12.3)%, (36.0 ± 8.7)%, 1.5 ± 0.6) (t=-2.879, -3.682, -3.340 respectively, all P<0.05), and returned to baseline when comparing to the preoperative level (t= 0.858, 0.758, -0.074 respectively, all P>0.05). NK cell began to recover at 24 h ((22.2 ± 12.6)%) comparing to the postoperative level (t= 2.941, P<0.05), but was still lower than the baseline (t=-2.249, P<0.05). Also, for all the above data, there were no difference between the two groups at any points (all P>0.05). There were no difference in hospital-stay time, antibiotic using time, the time to anal exhaust or defecate, postoperative fever, incision infection, neither other complications such as intestinal obstruction, urine retention, anastomotic fistula or intraperitoneal infection (all P>0.05). The incision infection rate was 0 in the propofol group while 14.3% in the sevoflurane group, which was quite clinically obvious though not statistically significant. CONCLUSIONS: Propofol may have less or shorter impact on immunity. However, whether anesthesia with propofol could be superior to that with sevoflurane for patients' immune function is still undetermined and needs further study.

Dry-processable carbon nanotubes for functional devices and composites.

Assembly of carbon nanotubes (CNTs) in effective and productive ways is of vital importance to their application. Recent progress in synthesis of CNTs has inspired new strategies for utilizing the unique physiochemical properties of CNTs in macroscale materials and devices. Assembling CNTs by dry processes (e.g., directly collecting CNTs in the form of freestanding films followed by pressing, stretching, and multilayer stacking instead of dispersing them in solution) not only considerably simplifies the processes but also avoids structural damage to the CNTs. Various dry-processable CNTs are reviewed, focusing on their synthesis, properties, and applications. The synthesis techniques are organized in terms of aggregative morphologies and microstructure control of CNTs. Important applications such as functional thin-film devices, strong CNT films, and composites are included. The opportunities and challenges in the synthesis techniques and fabrication of advanced composites and devices are discussed.

Joint Theoretical and Experimental Study of Stress Graphitization in Aligned Carbon Nanotube/Carbon Matrix Composites.

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.

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis.

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.

Carbon nanotube yarn strain sensors.

Carbon nanotube (CNT) based sensors are often fabricated by dispersing CNTs into different types of polymer. In this paper, a prototype carbon nanotube (CNT) yarn strain sensor with excellent repeatability and stability for in situ structural health monitoring was developed. The CNT yarn was spun directly from CNT arrays, and its electrical resistance increased linearly with tensile strain, making it an ideal strain sensor. It showed consistent piezoresistive behavior under repetitive straining and unloading, and good resistance stability at temperatures ranging from 77 to 373 K. The sensors can be easily embedded into composite structures with minimal invasiveness and weight penalty. We have also demonstrated their ability to monitor crack initiation and propagation.

Alloying effects on the plasticity of magnesium: comprehensive analysis of influences of all five slip systems.

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 〈a〉, and pyramidal 〈c + a〉 slip systems in twenty-one Mg alloys. Our results reveal that activation of 〈c + a〉 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.

Ultrastrong low-carbon nanosteel produced by heterostructure and interstitial mediated warm rolling.

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.

Ni Nanobuffer Layer Provides Light-Weight CNT/Cu Fibers with Superior Robustness, Conductivity, and Ampacity.

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.

The MiR-135b-BMAL1-YY1 loop disturbs pancreatic clockwork to promote tumourigenesis and chemoresistance.

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.

Effect of grain structure on Charpy impact behavior of copper.

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.