Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical ...activated M1 macrophages and alternatively activated M2 macrophages. The former typically exerts anti-tumor functions, including directly mediate cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; the latter can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis, and lead to tumor progression. Both M1 and M2 macrophages have high degree of plasticity and thus can be converted into each other upon tumor microenvironment changes or therapeutic interventions. As the relationship between TAMs and malignant tumors becoming clearer, TAMs have become a promising target for developing new cancer treatment. In this review, we summarize the origin and types of TAMs, TAMs interaction with tumors and tumor microenvironment, and up-to-date treatment strategies targeting TAMs.
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•Mn as a β-stabilizer has a stronger ability to inhibit the precipitation of α″ phase and ω phase.•The Young’s modulus of the TZMM alloys broadly matches that of human bone.•The ...corrosion resistance of the TZMM alloys is higher than that of CP-Ti.•The α′′/β interfaces in the TZMM alloys increases the sensitivity of pitting corrosion.
In order to reduce stress shielding effect of permanent implants, biomedical Ti-Zr-Mo-xMn (TZMM) alloys were developed and their microstructure, mechanical properties and corrosion behaviors were investigated in the present work. The results demonstrated that the Young’s modulus of the TZMM alloys was significantly reduced, matching the requirement of bone implant, whilst TZMM alloys revealed enhanced corrosion resistance in modified Fusayama saliva. The superior corrosion resistance of the TZMM alloys can be ascribed to the reduced anodic α″ phase resulting from the addition of manganese and the bi-layered passivation films comprising a ZrO2 barrier layer and a porous ZrO2-TiZrO4 top layer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With the hope to provide guidance to the design of additive manufactured porous orthopaedic implants and bone substitutes, three different topological porous structures (primitive, gyroid, bcc) with ...a porosity of 65% were designed and fabricated by selective laser melting using Ti-6Al-4V powders. The compressive and tensile properties of the porous scaffolds were investigated using quasi-static compression and tensile tests, respectively. Deformation behaviors of porous structures were analyzed by finite element simulation at different compression strains and loading condition. The Gyroid scaffolds have the highest compressive strength and tensile strength of 392.1 MPa and 321.3 MPa, respectively, almost two times higher than that of BCC scaffolds. Permeability of the scaffolds was measured using the falling head method and compared with the results of the computational fluid dynamics. The results showed that the permeability of the Gyroid scaffolds was about 20% that of the BCC scaffolds. It was suggested internal architecture for porous Ti alloy scaffold could significantly affect the mechanical stress and permeability.
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•Three different Ti-6Al-4V porous scaffolds (Primitive, Gyroid, Bcc) with 65% porosity were designed and manufactured by SLM.•The mechanical properties of porous scaffolds were determined by both compression and tensile tests.•The failure behaviors and permeability of porous scaffolds were analyzed by finite element simulation.•The largest cross-sectional area endows G scaffolds with the highest compressive strength and tensile strength.•Because of the simpler topological structure and bigger pore size, B scaffolds have outstanding permeability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surface texture and nitride coating have been proved as effective ways to improve the tribological properties of biomedical titanium alloys. However, the influence of surface texture and nitride ...coating on cells behavior, especially on the polarization of macrophages, was rarely reported. In this work, Ti-6Al-4V parts with designed rhombus surface texture were successfully prepared by selective laser melting process. Followed by post heating treatment in N2, uniform and dense nitride coatings on the textured surfaces consisted of TiN, Ti2N, TiN0.9 and N-containing solid solution with a thickness of ~5 μm were generated. The combination of surface texture and nitride coating reduced the frictional coefficient from 0.343 to 0.166, and significantly improved the wear resistance of the substrate. The nitride coating promoted the adhesion and proliferation of MC3T3-E1 cells in the early stages (1 d and 3 d). Textured surfaces provided larger area for cells growth that encouraged the cell adhesion and early spread. The significant increasing of the expression of Arg-1 and the ratio of CD206 positive cells (M2 phenotype) comparing with the uncoated group indicated that the nitride coating promoted the macrophages (Raw264.7 cells) polarization into anti-inflammatory type after co-culturing for 24 h. Surface texture combined with nitride coating further increased the ratio of CD206 positive cells and also reduced the inflammatory factors releasing.
•Designable textured nitride coating prepared by SLM followed with post heating treatment in N2•Significant reduction of the frictional coefficient and wear volume by textured nitride coating•Macrophages polarization into anti-inflammatory phenotype through nitride coating and 3D-printed texture
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the nonlinear creep characteristics of rocks under cyclic loading and unloading conditions, a nonlinear Kelvin model and damage viscoplastic model are proposed. The models are connected ...in series with a linear elastic body to establish a nonlinear damage creep model. The differential damage constitutive equations of the proposed creep model under one-dimensional and three-dimensional stress states are derived based on the creep mechanics and elasticity theory. The damage and unloading creep equations are then obtained based on the superposition principle, and a simple and feasible method for determining the model parameters is determined. Finally, the step cyclic loading and unloading creep test data for lherzolite and limestone are used to verify the rationality and feasibility of the nonlinear damage creep model. The results show that the theoretical creep curves of the nonlinear damage creep model are consistent with the experimental curves which indicates that the proposed model can not only determine the creep properties of lherzolite and limestone under cyclic loading and unloading but also determine the nonlinear characteristics of rocks in the transient and steady-state creep stages and particularly within the accelerating creep stage.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Occurrence of Colorectal cancer (CRC) is relevant with gut microbiota. However, role of IRF3, a key signaling mediator in innate immune sensing, has been barely investigated in CRC. Here, we ...unexpectedly found that the IRF3 deficient mice are hyper-susceptible to the development of intestinal tumor in AOM/DSS and Apc
min/+
models. Genetic ablation of IRF3 profoundly promotes the proliferation of intestinal epithelial cells via aberrantly activating Wnt signaling. Mechanically, IRF3 in resting state robustly associates with the active β-catenin in the cytoplasm, thus preventing its nuclear translocation and cell proliferation, which can be relieved upon microbe-induced activation of IRF3. In accordance, the survival of CRC is clinically correlated with the expression level of IRF3. Therefore, our study identifies IRF3 as a negative regulator of the Wnt/β-catenin pathway and a potential prognosis marker for Wnt-related tumorigenesis, and describes an intriguing link between gut microbiota and CRC via the IRF3-β-catenin axis.
With the rapid development of underground infrastructure and the uncertainty of its location, the possibility of damage due to nearby construction has increased. Thus, for the early warning of ...dangerous construction behaviors around underground facilities, this paper proposes a novel real-time distributed monitoring method with three levels, comprised of the terminal node, relay node, and server. Corresponding to these three monitoring levels, a vibration-based intelligent solution for recognizing the construction source is presented and compared with the traditional method. First, the blind source separation method was used to separate collected signals into a limited number of monitoring object sources; this helped to minimize the number of required classification categories and reduce the recognition uncertainty caused by signal mixing. Then, the mutual information (MI) method was used to select suitable vibration features, which were used as the input matrix for the resulting intelligent recognition. Finally, the construction behaviors were identified at the server based on returned features. Guided by this method, a sample dataset including pile-driving, train-operation, and environment-vibration signals was constructed and combined with a multi-layer perceptron (MLP) and a long short-term memory (LSTM) network. The effects of blind source separation and the MI method are discussed in depth in this paper.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Myeloid-derived suppressor cells (MDSCs) potently suppress the anti-tumor immune responses and also orchestrate the tumor microenvironment that favors tumor angiogenesis and metastasis. The molecular ...networks regulating the accumulation and functions of tumor-expanded MDSCs are largely unknown. In this study, we identified microRNA-494 (miR-494), whose expression was dramatically induced by tumor-derived factors, as an essential player in regulating the accumulation and activity of MDSCs by targeting of phosphatase and tensin homolog (PTEN) and activation of the Akt pathway. TGF-β1 was found to be the main tumor-derived factor responsible for the upregulation of miR-494 in MDSCs. Expression of miR-494 not only enhanced CXCR4-mediated MDSC chemotaxis but also altered the intrinsic apoptotic/survival signal by targeting of PTEN, thus contributing to the accumulation of MDSCs in tumor tissues. Consequently, downregulation of PTEN resulted in increased activity of the Akt pathway and the subsequent upregulation of MMPs for facilitation of tumor cell invasion and metastasis. Knockdown of miR-494 significantly reversed the activity of MDSCs and inhibited the tumor growth and metastasis of 4T1 murine breast cancer in vivo. Collectively, our findings reveal that TGF-β1-induced miR-494 expression in MDSCs plays a critical role in the molecular events governing the accumulation and functions of tumor-expanded MDSCs and might be identified as a potential target in cancer therapy.
The molecular mechanisms that drive the development of cardiac hypertrophy in hypertrophic cardiomyopathy (HCM) remain elusive. Accumulated evidence suggests that microRNAs are essential regulators ...of cardiac remodelling. We have been suggested that microRNAs could play a role in the process of HCM. To uncover which microRNAs were changed in their expression, microRNA microarrays were performed on heart tissue from HCM patients (n = 7) and from healthy donors (n = 5). Among the 13 microRNAs that were differentially expressed in HCM, miR‐451 was the most down‐regulated. Ectopic overexpression of miR‐451 in neonatal rat cardiomyocytes (NRCM) decreased the cell size, whereas knockdown of endogenous miR‐451 increased the cell surface area. Luciferase reporter assay analyses demonstrated that tuberous sclerosis complex 1 (TSC1) was a direct target of miR‐451. Overexpression of miR‐451 in both HeLa cells and NRCM suppressed the expression of TSC1. Furthermore, TSC1 was significantly up‐regulated in HCM myocardia, which correlated with the decreased levels of miR‐451. As TSC1 is a known positive regulator of autophagy, we examined the role of miR‐451 in the regulation of autophagy. Overexpression of miR‐451 in vitro inhibited the formation of the autophagosome. Conversely, miR‐451 knockdown accelerated autophagosome formation. Consistently, an increased number of autophagosomes was observed in HCM myocardia, accompanied by up‐regulated autophagy markers, and the lipidated form of LC3 and Beclin‐1. Taken together, our findings indicate that miR‐451 regulates cardiac hypertrophy and cardiac autophagy by targeting TSC1. The down‐regulation of miR‐451 may contribute to the development of HCM and may be a potential therapeutic target for this disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Broadband adaptive beamformers have been widely used in many areas due to their ability of filtering signals in space domain as well as in frequency domain. However, the space-time array employed in ...broadband beamformers requires presteering delays to align the signals coming from a specific direction. Because the presteering delays are direction dependent, it is difficult to make precise delays in practice. A common way to eliminate the presteering delays is imposing constraints on the weight vector of the space-time array. However, the structure of the constraint matrix is not taken into account in the existing methods, leading to a computational complexity of O(N2) when updating the weight vector. In this paper, we describe a new kind of constraint method in time domain that preserves the block diagonal structure of the constraint matrix. Based on this structure, we design an efficient weight vector update algorithm that has a computational complexity of O(N). In addition, the proposed algorithm does not contain matrix operations (only scalar and vector operations are involved), making it easy to be implemented in chips such as FPGA. Moreover, the constraint accuracy of the proposed method is as high as the frequency constraint method when the fractional bandwidth of the signal is smaller than 10%. Numerical experiments show that our method achieves the same performance of the state-of-the-art methods while keeping a simpler algorithm structure and a lower computational cost.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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