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Background: Brain arteriovenous malformation (bAVM) is an abnormal vascular mass with disordered arteriovenous connection. Endothelial KRAS mutation is common in bAVM. In vivo studies have demonstrated that mutations of KRAS in somatic cells can induce bAVM-like angiogenesis, suggesting that KRAS gene may play a key role in the development and progression of bAVM. Summary: In this article, we will provide a comprehensive review of action mechanisms of KRAS mutations in the development of bAVM and summarize potential targeting drugs for KRAS mutations in bAVM somatic cells. Key Message: KRAS mutation in human brain endothelial cells is a key driver in the pathogenesis of sporadic cerebral arteriovenous malformations. It is of great clinical importance to explore and summarize the changes in the signaling pathway induced by KRAS mutation, which may provide additional targets for the treatment of sporadic bAVM development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydrophilic and hydrophobic modified Ni foam packings are prepared by coating PDA. • The WCA of the modified Ni foam packing is controlled in the range of 0–151.5°. • Modified Ni foam packings have excellent mechanical and chemical stability. • A 35.6–160.2% enhancement ratio of k L a is obtained in μPBRs. • Models of k L a and f with WCAs are established. A micro-nano coating with controllable wettability is constructed on Ni foam using the dipping coating method, incorporating organic polydopamine (PDA) and 1H,1H,2H,2H-perfluorodecyltriethoxysilane, and inorganic SiO 2 nanoparticles. PDA has the properties of controlling wettability, strong adhesion, and abundant grafting sites. The water contact angle (WCA) of modified Ni foam is controlled in the range of 0–151.5°. The stability measurement displays that modified Ni foam packings exhibit excellent acid and alkali resistance as well as mechanical stability to fluid erosion under microenvironment. Compared with non-modified (131.5°) and superhydrophilic (0°) Ni foam packings, the maximum ratios of mass transfer enhancement for the superhydrophobic (151.5°) Ni foam packing are 35.6 % and 160.2 %, respectively. Empirical correlations of the gas–liquid mass transfer coefficient and friction factor are established considering the effect of the WCA, and errors between predicted values and experimental values are within ± 15 % and ± 10 %, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] A new mixed-mode cohesive zone model based on Lennard-Jones potential (LJCZM) is proposed to simulate the interface failure between graphene and epoxy matrix. The values of model parameters are obtained from a large number of molecular dynamics simulations, and a UMAT subroutine is programmed and validated to introduce this model into the ABAQUS platform. This process spans from the nanoscale to the microscale, which provides a new routine for the multiscale damage modeling of the graphene reinforced epoxy nanocomposite at microscale. In addition, the continuous damage phase-field model is used to simulate the matrix damage, and the values of model parameters are determined from the molecular dynamic simulations of the bulk epoxy at nanoscale. At last, the effects of parameters such as volume fraction, aspect ratio, orientation, and curvature of graphene nanoplatelets are investigated. The results indicate that the nanocomposite reinforced with high content and large aspect ratio graphene nanoplatelets presents the lower ultimate stress and fracture strain. In addition, the orientation and waviness of the graphene also significantly affect the mechanical properties of the nanocomposites. The nanocomposite reinforced with graphene platelets with greater waviness has higher stiffness and strength but lower toughness. The rationality and effectiveness of the model are verified through comparison with other existing results. [ABSTRACT FROM AUTHOR]

The present investigation aims to identify the flexural performance of two-span concrete beams reinforced with hybrid carbon fiber reinforced polymer (CFRP) and steel bars. By applying a finite element analysis, a comprehensive numerical assessment is performed. The investigated variables are Af/Ar (Af = area of CFRP bars; Ar = total area of CFRP/steel bars), load pattern (symmetrical and unsymmetrical loading) and load type (center-point, third-point and uniform loading). The results show that beams with Af/Ar of 0.25 show 16.0% and 11.3% higher ultimate load at symmetrical and unsymmetrical loading, respectively, than beams with Af/Ar of 0.0 (i.e., beams with steel bars), but the change in ultimate load is not apparent when varying Af/Ar between 0.25 and 1.0. Unsymmetrical loading causes 6.0–15.0% greater deflection capacities than the symmetrical one. When Af/Ar increases from 0.0 to 1.0, moment redistribution at symmetrical loading is decreased significantly by 62%, while the redistribution variation is marginal at unsymmetrical loading. In addition, the applicability of two equations based on the ultimate strain in tensile bars for predicting moment redistribution is evaluated. It is generally shown that these equations can account for the influence of Af/Ar and load type. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a physiologically focused radiation therapy that relies on nuclear capture and fission processes. BNCT is regarded as one of the most promising treatments due to its excellent accuracy, short duration of therapy, and low side effects. The creation of novel boron medicines with high selectivity, ease of delivery, and high boron‐effective load is a current research topic. Herein, boron‐containing carbon dots (BCDs) and their human serum albumin (HSA) complexes (BCDs‐HSA) are designed and synthesized as boron‐containing drugs for BNCT. BCDs (10B: 7.1 wt%) and BCDs‐HSA exhibited excitation‐independent orange fluorescent emission which supported the use of fluorescence imaging for tracking 10B in vivo. The introduction of HSA enabled BCDs‐HSA to exhibit good biocompatibility and increased tumor accumulation. The active and passive targeting abilities of BCDs‐HSA are explored in detail. Subcutaneous RM‐1 tumors and B16‐F10 tumors both significantly decrease with BNCT, which consists of injecting BCDs‐HSA and then irradiating the area with neutrons. In short, this study provides a novel strategy for the delivery of boron and may broaden the perspectives for the design of boron‐containing carbon dots nanomedicine for BNCT. [ABSTRACT FROM AUTHOR]

• A new inverse identification framework is established to determine the parameters of cohesive zone models; • The framework employs the multi-island genetic algorithm for optimal parameter optimization; • An objective function is formulated using two independent metrics; • The interface debonding length is adopted to uniquely determine the debonding properties; • The robustness and accuracy of the proposed framework is validated by experiments. Composite interfaces are commonly simulated by cohesive zone models with the key challenge being the calibration of interfacial parameters. A novel inverse identification framework is presented in this paper to determine the interface parameters of cohesive zone models. This approach employs the multi-island genetic algorithm to obtain the key parameters of cohesive zone model which can reproduce the experimental observations. Utilizing two independent metrics, namely the load-displacement response and the debonding length history, an objective function is formulated to give the framework inherent robustness. The interface debonding length is used to uniquely determine the debonding properties of the specimen. To demonstrate the feasibility of the proposed framework, the strength-based cohesive zone model is taken as an example. The inverse algorithm is adopted to identify the interface parameters of both the double cantilever beam (DCB) experiments and the fixed-ratio mixed-mode (FRMM) tests. The robustness, accuracy and sensitivity of the framework are validated through the double cantilever beam test. The findings indicate that the numerical results align closely with the experimental data, confirming that the interface parameters identified by the proposed framework can reproduce the experimental results. [ABSTRACT FROM AUTHOR]

This study develops a sequential multiscale model to investigate the interface failure of graphene-reinforced epoxy nanocomposites. The molecular dynamics simulations are carried out to track the graphene-epoxy interface behavior through normal opening and tangential sliding modes modeling at nanoscale. Four kinds of functional groups on the graphene including –OH, –NH2, –CH3 and –COOH are considered. The traction-separation law in the normal direction and the shear-lag model in the tangential direction are used to mimic the interface behavior. Furthermore, the scaled boundary finite element method in collaboration with a new hybrid quadtree algorithm is used to discretize the nanocomposite representative volume element at microscale. In addition to the functional group types, the volume fraction and aspect ratio of the graphene nanoplatelets are taken into account in the microscale simulation. The results show that the addition of functional groups to graphene can greatly improve the load-bearing capacity of the interface between nanoplatelets and epoxy resin. Meanwhile, the reinforcement effect of nanoplatelets is related to their aspect ratio and volume fraction. The efficiency and accuracy of the proposed model are validated by comparing the results with traditional finite element method. This study provides a theoretical support and guidance for the design and fabrication of graphene reinforced nanocomposites. [ABSTRACT FROM AUTHOR]

Based on the unified strength criterion, the plane strain elastic-plastic bending of a linear strain hardening curved beam is analyzed in this study. The solutions for the properties of plane strain bending of the curved beam are obtained, taking into account the strength difference effect and the intermediate principal stress effect. Those solutions based on different strength criteria, such as Tresca, von Mises, Mohr-Coulomb, TS and GTS, are the special cases (Tresca, Mohr-Coulomb, TS and GTS) or linear approximation (von Mises) of the present solutions. Besides, a series of solutions that can take account of the strength difference effect and the differing effect of intermediate principal stress can be obtained from it. Consequently, the present solutions are suitable for various kinds of engineering materials. The influences of strength difference and intermediate principal stress on the two critical bending moments, the two interface radii between the elastic and plastic regions, and the radial displacements and stresses of points at the symmetrical plane of the curved beam are discussed comprehensively. It can be concluded from the analyses that the strength difference effect and the intermediate principal stress effect on the properties of plane strain bending of the curved beam are considerable and cannot be ignored. [ABSTRACT FROM AUTHOR]

The general governing equation for transverse vibration of an axially pretensioned viscoelastic nanobeam embedded in elastic substrate medium is formulated on the basis of the Bernoulli–Euler beam theory and the Kelvin model. The factors of structural damping, initial axial tension, surrounding medium, small size, surface elasticity and residual surface tension are incorporated in the formulation. The explicit expression is obtained for the vibrational frequency of a simply supported nanobeam. The impacts of these factors on the properties of transverse vibration of the nanobeam are discussed. It is demonstrated that the dependences of natural frequency on the structural damping, surrounding medium, small size, surface elasticity and residual surface tension are significant, whereas the effect of initial axial tension on the natural frequency is limited. In addition, it can be concluded that the energy dissipation of transverse vibration of the viscoelastic nanobeam is related to the small size effect and structural damping. [ABSTRACT FROM AUTHOR]

Array detection method is widely used for measuring the far field laser centroids. The influence of array detector's aperture and dynamic range on the far field laser power was analyzed on the basis of the measurement method and measurement process for the laser spot centroid. The effect of array detector's spatial resolution and spatial duty ratio on the far field laser spot centroid was simulated, and the results were verified by performing experiments, enabling the determination of the technology requirements for the array detector. The expression for the laser spot centroid uncertainty was deduced on the basis of the uncertainty theory and laser spot centroid expression, and the sources of uncertainty were analyzed. The results will be of great importance for measuring the far field laser spot centroids and designing array detectors. [ABSTRACT FROM AUTHOR]

This work assesses the flexural performance of prestressed concrete beams with external carbon fiber-reinforced polymer (CFRP) tendons, focusing on tendon-related variables. A finite element analysis (FEA) method is verified. A numerical parametric analysis of prestressed concrete beams with external CFRP tendons is carried out. Four tendon-related variables are considered, namely, the area, initial prestress, depth and elastic modulus of tendons. The analysis shows that flexural ductility decreases as the tendon area, initial prestress or elastic modulus increases but is insensitive to the tendon depth. The ultimate tendon stress increment (Δσp) is influenced by all of the four variables investigated. JGJ 92-2016 (Chinese technical specification for concrete structures prestressed with unbonded tendons) significantly underestimates Δσp and, hence, is over-conservative for the strength design of these beams. An equation is proposed for calculating Δσp, taking into account all four variables investigated. An analytical model is then developed to estimate the flexural strength (Mu) of prestressed concrete beams with external CFRP tendons. The proposed analytical model shows good agreement with FEA, i.e., the mean discrepancy for Δσp is 0.9% with a standard deviation of 11.1%; and the mean discrepancy for Mu is −1.6% with a standard deviation of 2.1%. [ABSTRACT FROM AUTHOR]

This study aimed at examining the feasibility of using fiber-reinforced polymer (FRP) rebars instead of steel ones in prestressed concrete beams (PCBs) with external FRP tendons. By applying an experimentally validated program, numerical tests were performed on simply supported PCBs, with investigated variables including rebars' type and area. Three types of rebars were considered, i.e., carbon, glass FRPs (CFRP, GFRP), and reinforcing steel. The ratio of tensile rebars ranged from 0.22% to 2.16%. The results indicated that the beams with CFRP rebars exhibited better crack mode and higher ultimate load than the beams with GFRP or steel rebars. GFRP rebars led to considerably higher ultimate deflection and tendon stress increment than steel rebars. In addition, several models for calculating the ultimate stress in unbonded tendons were assessed. An analytical model was also proposed to predict the tendon stress at ultimate and flexural strength in externally PCBs with steel and FRP rebars. The model predictions agreed well with the numerical results. [ABSTRACT FROM AUTHOR]

Diabetes mellitus can cause cognitive impairments, a state between normal aging and dementia. Effective clinical interventions are urgently needed to prevent or treat this complication. Liraglutide as a glucagon–like peptide 1 analog has been shown to exert memory-enhancing and neuroprotective effects on neurodegenerative diseases. This study aims to investigate the neuroprotective effects of liraglutide in streptozotocin (STZ)-induced diabetic mice with cognitive deficits. Male C57BL/6J mice were intraperitoneal injected with STZ (65 mg/kg body weight daily for 5 days) to induce type 1 diabetes model. Then the mice were treated with liraglutide (250 mg/kg/day, for 6 weeks) or saline. Weekly changes of body weight and fasting blood glucose were measured. Cognitive performance was evaluated by Morris water maze test. The ultrastructure of hippocampus was observed by transmission electron microscope. The superoxide dismutase activities and malondialdehyde levels in the hippocampus were detected by biochemistry assay. Apoptosis-related proteins and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) signaling were detected by Western blotting. We found that STZ-induced diabetic mice exhibited impaired learning and memory, ultrastructure damage of hippocampal neurons and synapses, exacerbated oxidative stress and neuronal apoptosis, as compared to the control mice. These effects were attenuated by the treatment with liraglutide. Furthermore, liraglutide reversed diabetes-induced alterations in PI3K/Akt signaling pathway that plays an essential role in modulating neuronal survival, apoptosis and plasticity. These data suggest that the neuroprotective effects of liraglutide on diabetes-induced cognitive impairments are associated with the improvements of hippocampal synapses and inhibition of neuronal apoptosis. • Liraglutide alleviates cognitive impairments in STZ-induced diabetic mice. • Liraglutide mitigates the hippocampal and synaptic injuries of diabetic mice. • Liraglutide exerts anti-oxidative and anti-apoptotic effects on diabetic mice. [ABSTRACT FROM AUTHOR]

Micro-structures of fibre reinforced composites play a pivotal role in their damage, fracture and failure mechanisms. This study first carried out ex-situ micro X-ray Computed Tomography (μXCT) tests of three small ultra-high-performance fibre reinforced concrete (UHPFRC) beams under progressive three-point bending. The first two beams were continuously loaded until failure and their central regions with the main flexural crack were scanned by μXCT before and after the test. The third beam was subjected to five cycles of loading-unloading until failure, and was scanned by μXCT after each unloading. The 3D μXCT images with 30 μm voxel resolution were then processed and analysed, and the spatial distribution, number, orientation and dimension of pores and fibres were statistically quantified. The micro-scale failure mechanisms, such as fibre bridging of cracks, fibre-matrix interfacial slipping and debonding, and matrix failure, were visualised and analysed. The μXCT images of the first two beams were then segmented and directly converted to meso-scale finite element models based on orientation-dependent bond-slip relations for the fibre-matrix interfaces and continuum damage plasticity for the matrix. The simulated load-displacement curves, fracture processes and final crack morphologies were found in excellent agreement with the tests. It was also found that the position, dimension and orientation of fibres and pores have significant effects on the damage and fracture initiation and evolution from both the tests and the simulations. • Ex-situ μXCT tests of UHPFRC beams under bending are carried out for the first time. • The whole process of 3D crack initiation and evolution is obtained with various micro/meso-scale failure mechanisms captured by μXCT images. • Internal 3D microstructures (pores and fibres) are statistically quantified and are used to build mesoscale FE models of high fidelity. • The simulated load-displacement curves, fracture processes and final crack morphologies are found in excellent agreement with the tests. • The distribution and orientation of fibres and pores are found to affect damage and fracture evolution from both the tests and the simulations. [ABSTRACT FROM AUTHOR]

This paper assesses the impact of adopting carbon- or glass-fiber-reinforced polymer (CFRP or GFRP) instead of steel rebars on the redistribution of moments in prestressed concrete beams (PCBs) with external CFRP tendons. A numerical program is introduced, and numerical simulations are performed on two-span continuous beams with steel, CFRP or GFRP rebars of various areas, i.e., Ar2 = 360–3560 mm2, and Ar1/Ar2 = 1.5, where Ar1 and Ar2 are areas of tensile rebars over the positive and negative moment zones, respectively. The results show the moment redistribution is contributed by concrete cracking only for the beams with fiber-reinforced polymer (FRP) rebars, and by concrete cracking and steel yielding for the beams with steel rebars. As a result, the use of FRP rebars leads to a substantially lower moment redistribution than in steel rebars. It is also demonstrated that Eurocode 2, CSA A23.3-04 and ACI 318-19 fail to reflect the rebar influence on moment redistribution in PCBs with external tendons. A simplified equation for the quantification of moment redistribution in externally PCBs with steel and FRP rebars is recommended, which yields accurate and conservative predictions. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) generated by NADPH oxidase-4 (NOX4) have been shown to initiate lung fibrosis. The migration of lung fibroblasts to the injured area is a crucial early step in lung fibrosis. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang(1-7)]/Mas axis, which counteracts the ACE/angiotensin II (AngII)/angiotensin II type 1 receptor (AT1R) axis, has been shown to attenuate pulmonary fibrosis. Nevertheless, the exact molecular mechanism remains unclear. Aims: To investigate the different effects of the two axes of the renin-angiotensin system (RAS) on lung fibroblast migration and extracellular matrix accumulation by regulating the NOX4-derived ROS-mediated RhoA/Rho kinase (Rock) pathway. Results: In vitro, AngII significantly increased the NOX4 level and ROS production in lung fibroblasts, which stimulated cell migration and α-collagen I synthesis through the RhoA/Rock pathway. These effects were attenuated by N-acetylcysteine (NAC), diphenylene iodonium, and NOX4 RNA interference. Moreover, Ang(1-7) and lentivirus-mediated ACE2 (lentiACE2) suppressed AngII-induced migration and α-collagen I synthesis by inhibiting the NOX4-derived ROS-mediated RhoA/Rock pathway. However, Ang(1-7) alone exerted analogous effects on AngII. In vivo, constant infusion with Ang(1-7) or intratracheal instillation with lenti-ACE2 shifted the RAS balance toward the ACE2/Ang(1-7)/Mas axis, alleviated bleomycin-induced lung fibrosis, and inhibited the RhoA/Rock pathway by reducing NOX4-derived ROS. Innovation : This study suggests that the ACE2/Ang(1-7)/Mas axis may be targeted by novel pharmacological antioxidant strategies to treat lung fibrosis induced by AngII-mediated ROS. Conclusion: The ACE2/Ang(1-7)/Mas axis protects against lung fibroblast migration and lung fibrosis by inhibiting the NOX4-derived ROS-mediated RhoA/Rock pathway. Antioxid. Redox Signal. 22, 241-258. [ABSTRACT FROM AUTHOR]

This article presents a retracted article titled "Synthesis and Characterization of Gemini Surfactants with Two Sulfonate Groups, Two hydroxyl, and Two Lipophilic Alkyl Chains," on request from all authors.