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[Display omitted] • A consistent damage evolution rule is developed for the uniform expression of damage evolution of UHPC-CA at varying loading conditions. • A damage constitutive model is established for UHPC-CA with the driving and alleviating effects induced by the inclusions of coarse aggregate and steel fiber taken into consideration. • A user-defined UMAT subroutine is compiled for the numerical implementation of the proposed model. A suitable constitutive model for describing the mechanical behaviors of ultra-high performance concrete (UHPC) under various loading histories plays a vital role in analyzing its structural performance. In this work, a consistent elastoplastic damage model is developed for UHPC containing coarse aggregate (UHPC-CA) subjected to static and fatigue loads, in which the driving and alleviating effects induced by the inclusions of coarse aggregate and steel fiber are considered. For damage evolution, based on the acting mechanism of the non-uniformity of stress wave propagation determined by the loading rate on the mechanical responses of UHPC-CA, the loading rate is skillfully integrated into the damage evolution rule to achieve the consistent description of mechanical behaviors of UHPC-CA under static and fatigue loading conditions. Regarding plasticity growth, an empirical plastic deformation model is adopted to improve the computational efficiency of structural nonlinear analysis. To verify the applicability of the proposed model, a user-defined UMAT subroutine is further developed for the subsequent numerical implementation. The comprehensive comparisons between the numerical predictions and independent experimental results at both the material level and structural level solidly demonstrate the capacity of the consistent model to capture the main features concerning the mechanical performance of UHPC-CA subjected to different loading paths. [ABSTRACT FROM AUTHOR]

Sanguinarine is a quaternary ammonium benzophenanthine alkaloid found in traditional herbs such as Chelidonium , Corydalis , Sanguinarum , and Borovula. It has been proven to possess broad-spectrum biological activities, such as antitumor, anti-inflammatory, antiosteoporosis, neuroprotective, and antipathogenic microorganism activities. In this paper, recent progress on the biological activity and mechanism of action of sanguinarine and its derivatives over the past ten years is reviewed. The results showed that the biological activities of hematarginine and its derivatives are related mainly to the JAK/STAT, PI3K/Akt/mTOR, NF-κB, TGF-β, MAPK and Wnt/β-catenin signaling pathways. The limitations of using sanguinarine in clinical application are also discussed, and the research prospects of this subject are outlined. In general, sanguinarine, a natural medicine, has many pharmacological effects, but its toxicity and safety in clinical application still need to be further studied. This review provides useful information for the development of sanguinarine-based bioactive agents. [Display omitted] • Multiple pharmacological activities of sanguinarine and its derivatives were concluded. • Mechanism of action of sanguinarine and its derivatives were detailly reviewed. • Outlooks about sanguinarine-related research were presented and discussed. [ABSTRACT FROM AUTHOR]

Uncertainty in the failure mechanism and damage evolution of recycled aggregate concrete (RAC) due to complex components largely restricts the practical application of RAC in load-bearing members. In this study, a feasible concurrent macro-meso numerical approach is proposed to investigate the seismic performance of prefabricated recycled concrete shear wall (PRCSW), with an emphasis on revealing the failure mechanisms at both the material and structural scales. Specifically, RAC is regarded as a multiphase heterogeneous material that is represented by an elaborative mesoscale random aggregate model consisting of six phases. The collective mechanical responses of RAC are reasonably captured under various replacement rates of recycled aggregate (R ra = 0, 30%, 50%, 70%, and 100%) and volume fractions of old mortar (V om = 12%, 16%, 20%, and 24%). In addition to this, a practical concurrent macro-mesoscale model of PRCSW is established, in which the mesoscale model of RAC is exclusively exploited in the critical vulnerable regions (e.g., concealed beam, column, and bottom of wall limb), while the macroscale model is utilized for the remaining regions, striking a balance between computational efficiency and accuracy. To facilitate the numerical implementation, a highly effective approach using Linear Multi-Point Constraint (LMPC) is adopted to establish connections between models operating at varying scales, thus allowing for the simulation in parallel. Upon such a bottom-up numerical analysis, the results show that due to the significantly weakened properties of old mortar and the inclusion of associated interfacial transition zones (ITZs), the damage development and mechanical performance of RAC are quite different from that of ordinary concrete, manifesting as the amplified accumulation of damage around aggregates and severe fractures of recycled aggregates. Although the addition of RAC (R ra increases from 0 to 100%) is found to slightly weaken the horizontal seismic bearing capacity of PRCSW (decreased by 8.57%), its structural deformation capacity, however, is obviously compensated (increased by 34.42%), resulting in a marginal variation of energy dissipation capacity. The findings facilitate the utilization of substantial RAC in load-bearing members with higher confidence. • The failure mode and damage mechanism of RAC were revealed using a mesoscale model. • The seismic performance of PRCSW was studied upon a concurrent macro-mesoscale numerical approach. • A novel method upon LMPC was adopted for the concurrent macro-mesoscale numerical simulation. [ABSTRACT FROM AUTHOR]

This paper presents a study on the compressive behavior of a novel type of highly deformable hybrid FRP tubular columns. The columns consist of an FRP tube filled with large-size recycled concrete lumps (RCLs) as aggregates and flowable grout as the binding material, and are thus termed FRP-RCL-Grout (F-R-G) columns. The use of large-size RCLs (e.g., up to 63 mm RCLs for 200 mm circular columns) leads to a relatively high recycling ratio and facilitates the manufacturing process. The flowable grout can be easily poured/pumped into the FRP tube, leading to ease of construction, while the FRP tube acts as an effective lateral confining device. The experimental part of the study involved compression tests on F-R-G columns and similar columns for comparison, with the main test variables being the FRP tube thickness, the size of the RCLs, the compressive strength of the concrete for producing RCLs and the WP ratio of the grout. The test results showed that F-R-G columns possess excellent structural behavior including ample ductility, and clarified the effects of the key parameters. In addition, based on the test results, a simple yet accurate model is proposed to predict the strength of F-R-G columns. • A novel FRP tubular column form incorporating recycled concrete lumps and flowable grout is investigated. • The novel column is highly deformable with ample ductility. • The novel column form provides an effective method of using recycled concrete lumps for structural applications. • The use of flowable grout highly eases the construction of the column. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic polyhydramnios (IPH) is an abnormal increase in amniotic fluid volume (AFV). This condition has unknown etiologies and is associated with various adverse pregnancy outcomes including maternal and fetal complication. This study aims to establish a comparative proteome profile for the human amniotic fluid (AF) of IPH and normal pregnancies and identify the responsible mediators and pathways that regulate AFV.Methods: We first employed coupled isobaric tags for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analysis to examine the differentially expression proteins (DEPs) in the AF of IPH and normal pregnancies. Second, CUL5, HIP1, FSTL3, and LAMP2 proteins were selected for verification in amnion, chorion, and placental tissues by Western blot analysis.Results: We identified 357 DEPs with 282 upregulated and 75 downregulated. Bioinformatics analysis revealed that cell, cellular process, and binding were the most enriched Gene Ontology terms. Amoebiasis, hematopoietic cell lineage, and NF-kappa B signaling pathway were the top significant pathways. In the verification procedure, FSTL3 protein had a highly significant expression in the amnion, chorion, and placentas of IPH and normal AFV groups (p < 0.05).Discussion: Our results provide new insights into idiopathic polyhydramnios and offer fundamental points for future studies on AFV. [ABSTRACT FROM AUTHOR]

• The effects of steel-polypropylene hybrid fiber on the bond strength of deformed bar to concrete were investigated. • The mechanism of fiber reinforcement at multi-scale and multi-stages was discussed. • An analytical model for predicting the ultimate bond strength of HFRC specimen were proposed. This paper deals with the bond strength of deformed bar embedded in steel-polypropylene hybrid fiber reinforced concrete (HFRC) matrix. The benefits of hybrid fibers were evaluated through a series of monotonic/cyclic pull-out testing on 72 specimens. The influences of fiber characteristics, i.e. the volume fraction and aspect ratio, on the failure mode and the complete bond-slip responses were analyzed. Upon a simplified spring model, the effects of fiber reinforcement at different loading stages were further discussed. The results showed that for a well-confined HFRC specimen, the cyclic bond response at the pre-peak stage almost approached its monotonic response with slight reduction in the ultimate bond strength. Compared to the specimen made with plain concrete, the introduction of hybrid fibers could exert obvious positive influences on the bond strength, due to the synergetic effects in inhibiting the propagation of cracks at multi-scale and multi-stages. Finally, an analytical model was proposed to estimate the ultimate bond strength, in which the effects of fiber reinforcement, stirrup confinement and geometrical shape of deformed bar were taken into consideration. The model was subsequently well validated by various independent experimental results. [ABSTRACT FROM AUTHOR]

• A stochastic damage model based on an innovative spring system is proposed. • A random variable that specifies the failure displacement of micro spring elements is suggested. • The path-dependence and pressure-sensitivity of bond response are discussed. The bond behavior of reinforcing bars embedded in concrete has been widely evidenced to exhibit an obvious nonlinearity with a high degree of randomness. To cope with this phenomenon, a stochastic damage model based on an innovative spring system is proposed in this paper. To describe the stochastic feature of bond response, the model introduces a random variable that specifies the failure displacement of micro spring elements, and meanwhile, two evolution laws for the interfacial damage and sliding are also defined respectively. Moreover, the effects of loading history and lateral stress are incorporated into the model, which is capable of reproducing the path-dependence and pressure-sensitivity of bond behavior faithfully. Finally, the model is numerically implemented by exploiting an implicit backward Euler scheme and verified by a number of numerical trial tests and independent experimental results. The satisfactory validations may provide a beneficial reference to bring the stochastic nature of nonlinear interfacial debonding into future theoretical studies on the structural response of reinforced concrete structures. [ABSTRACT FROM AUTHOR]

Highlights • Two novel evolution laws for damage variables and hardening plasticity are developed. • A function that can predict the reduction of bond strength reasonably is proposed. • Only a few identifiable parameters with sound physical meanings are required. Abstract An appropriate bond stress-slip model is of great significance in accurate prediction of the overall responses of a structure in terms of stiffness, bearing capacity, crack pattern distribution, as well as durability in whole lifecycle. In this paper, a damage-plasticity model within the thermodynamic framework is presented, aiming to simulate the bond behavior of steel reinforcement embedded in a well-confined fiber reinforced concrete. With the motivation to reproduce the bond responses faithfully, two novel evolution laws for internal damage variables and hardening plasticity are developed respectively. Meanwhile, a bond reduction function is also proposed, which is capable of reflecting the degradation law in two directions reasonably during the loading history. The model requires only a few identifiable parameters obtained from simple experiments, and each of the parameters has a clear physical meaning. Subsequently, the model is numerically implemented by means of a backward Euler algorithm, and the output is verified by various experimental results from literature. The comparisons with a satisfactory accuracy firmly testify the feasibility of the proposed approach, which pave the way for further theoretical studies on the structural response of FRC structures. [ABSTRACT FROM AUTHOR]

Abstract Targeting delivery system has been widely used in packaging drugs for medical therapies attributed to its high efficiency and efficacy. A Traditional Chinese Medicine (TCM) formula consisting of Herba Epimedii has previously been shown to effectively treat postmenopausal osteoporosis. We have subsequently found that icaritin, which was a flavonoid isolated from both Herba Epimedii and its serum metabolites after oral administration, inhibited the adipogenic capacity of bone mesenchymal stem cells (BMSCs) while promoted their osteogenesis. However, previous pharmacokinetic analyses have shown that icaritin had a short half-life in blood and only trace amounts of the molecule reach the bone tissue. To overcome this limitation, we developed a bone-targeting liposome containing an oligopeptide of eight aspartate residues (Asp8), which had previously been shown to specifically target the bone, encapsulating icaritin. In vivo, we found that the Asp8-icaritin-liposome enhanced bone formation in ovariectomized mice compared to an icaritin-liposome control lacking the Asp8 moiety. Through in vitro mechanistic studies we further found that icaritin inhibited adipogenesis through an Akt/GSK-3β/β-catenin signaling pathway. Taken together, our study shows that Asp8-liposome as a bone-targeting delivery system is effective to carry an osteogenic phytomolecule for facilitating and enhancing its therapeutic effects on the prevention of estrogen depletion-induced osteoporosis. [ABSTRACT FROM AUTHOR]

FRP-confined concrete-encased cross-shaped steel columns (FCCSCs) are a new form of hybrid columns recently developed at the University of Wollongong. An FCCSC consists of a square FRP outer tube, a cross-shaped steel section and concrete filled in between. This sectional configuration ensures that the concrete is very effectively confined despite the square shape of the column. In addition, the cross-shaped steel section serves as the ductile longitudinal reinforcement for loads in the two lateral directions and its possible buckling is constrained by the FRP outer tube and the concrete, leading to a column that is highly ductile. In this paper, results from a series of stub column tests are presented to demonstrate the concept of the new column form. The experimental program involved the testing of FCCSC specimens as well as four types of similar column forms, namely, square FRP-confined plain concrete columns (SFCPCs), circular FRP-confined plain concrete columns (CFCPCs), concrete-encased cross-shaped steel columns and square plain concrete columns. The test results confirmed the excellent performance of FCCSCs. The test results also showed that compared with the concrete in SFCPCs and that in CFCPCs, the concrete in FCCSCs has a much larger ultimate axial strain and a larger compressive strength, when the same FRP tube is used. [ABSTRACT FROM AUTHOR]

• Reliable 3D finite element models are developed for FRP-confined concrete-encased cross-shaped steel columns (FCCSCs). • An in-depth understanding on the complex confinement mechanism of FCCSCs is achieved. • The effects of key parameters on the mechanism and behaviour of FCCSCs are thoroughly examined. Fibre-reinforced polymer (FRP)-confined concrete-encased cross-shaped steel columns (FCCSCs) are an emerging type of hybrid columns. In an FCCSC, the concrete is subjected to combined confinement from the steel section and the FRP tube, leading to an enhanced load capacity and excellent ductility of the column. While several recent experimental studies have demonstrated the excellent structural performance of FCCSCs, the complex confinement mechanism behind their structural behaviour has not been clarified or thoroughly examined. This paper presents a comprehensive study aiming to investigate the confinement mechanism of FCCSCs. In this paper, the experimental observations of FCCSCs are first summarized, followed by three-dimensional FE modelling of the columns. The FE models, after being verified against the test results in various aspects, are used for a systematic parametric study. In this study, the complex interaction between the three components of FCCSCs (i.e., FRP tube, steel section and concrete) is illustrated explicitly and the effects of key parameters (i.e., flange width, flange thickness, web thickness and FRP tube thickness) are examined separately and thoroughly, leading to an in-depth understanding of the confinement mechanism of FCCSCs. In particular, through the examination on the distribution of steel flange-to-concrete normal pressure, it is shown quantitatively that the variations of the dimensions of the steel section in a practically wide range have only marginal effects on its confinement to the concrete, while the increase of FRP tube thickness tends to reduce the confinement effect from the steel section. [ABSTRACT FROM AUTHOR]

• A clinkerless ultra-high strength concrete (UHSC) was developed at room temperature. • The damage evolution and plasticity development of UHSC were investigated. • A unified temperature-dependent constitutive model was proposed. In this work, the uniaxial compressive behaviors of alkali-activated slag-based ultra-high strength concrete (AAS-UHSC) subjected to different temperatures were investigated, with an emphasis on the temperature-dependent stress-strain relation. To this end, 104 cylinder specimens with three steel fiber contents (0.5%, 1.0%, and 1.5%) and two water-to-binder (W/B) ratios (0.20 and 0.25) were tested upon the monotonic and cyclic compression performed at ambient temperature (20 ℃) and four elevated temperatures (200, 400, 600, and 800 ℃). The test results showed that the mechanical properties of AAS-UHSC in terms of elastic modulus, ultimate strength, energy dissipation, and post-peak softening can be effectively improved with the fiber inclusion, regardless of the W/B ratio. Moreover, AAS-UHSC exhibited a quite different plastic strain evolution law featured as two discontinuous stages due to the damage localization and possessed better energy dissipation capacity compared to OPC-based concretes. After being exposed to elevated temperatures, a consistent decline in compressive strength was observed as the temperature increased, with residual strength at 800 ℃ remaining around 10% of the ultimate compressive strength at 20 ℃. Based on the test results, a unified empirical temperature-dependent model was proposed to capture the main features of the constitutive compressive stress-strain relations of AAS-UHSC. The fairly good comparisons between test results and model predictions in different loading scenarios demonstrated a compromise between the accuracy and the generality of the model and contributed a beneficial addition to the understanding of nonlinear responses of AAS-UHSC. [ABSTRACT FROM AUTHOR]

EGFRvⅢ is an established target for immunotherapy of glioblastoma (GBM). Current study aims to explore the efficacy of EGFRvⅢ-targeted immunotoxin combined with temozolomide (TMZ) or T cell-engaged bispecific antibody for the treatment of GBM. We generated three rabbit monoclonal antibodies (R1, R2, and R6) that specifically bound to EGFRvⅢ, but not EGFR, with high affinity. Immunotoxins were made by fusing the scFv of these antibodies with engineered Pseudomonas exotoxin PE24. The in vitro cytotoxicity and specificity of the immunotoxins was rigorously validated by EGFRvⅢ and EGFR-expressed cell lines. The in vivo efficacy of immunotoxin monotherapy and in combination with TMZ or EGFRvⅢ-targeted bispecific antibody was evaluated in orthotopic and subcutaneous xenograft mouse models. EGFRvⅢ immunotoxins potently killed U87, U251 and GL261 cells that were forcefully expressing EGFRvⅢ, with IC 50 values bellow 1.2 ng/ml. In a subcutaneous model, multiple intratumoral injections of immunotoxin at a dose of 2 mg/kg resulted in complete tumor regression in 3/5 of mice. In a C57BL/6 orthotopic glioblastoma model transplanted with GL261 cells that expressed a mouse version of EGFRvⅢ, two injections of 10 micrograms of immunotoxin in the lateral ventricles significantly improved the survival, with 2/5 mice being completely cured. Furthermore, in a subcutaneous xenograft model transplanted with EGFRvⅢ-expressed U87 cells, a single intratumoral injection of immuntoxin followed by i.v. injections of TMZ or EGFRvⅢ-targeted bispecific antibody achieved complete regression in mice. Taken together, EGFRvⅢ immunotoxin combined with TMZ or T cell-engaged bispecific antibody offers promise for curative treatment of GBM. [Display omitted] • Three new monoclonal antibodies highly specific to EGFRvIII were generated. • Intratumoral injections of EGFRvIII immunotoxin eradicated tumors in mouse models. • Combination of EGFRvIII immunotoxin and TMZ had synergistic effect. • Combination of EGFRvIII immunotoxin with bispecific antibody had better efficacy. • Afore mentioned combinations warrant clinical trial for treatment of glioblastoma. [ABSTRACT FROM AUTHOR]