A major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated ...mineralization process that takes advantage of disorder-order interplay using elastin-like recombinamers to program organic-inorganic interactions into hierarchically ordered mineralized structures. The materials comprise elongated apatite nanocrystals that are aligned and organized into microscopic prisms, which grow together into spherulite-like structures hundreds of micrometers in diameter that come together to fill macroscopic areas. The structures can be grown over large uneven surfaces and native tissues as acid-resistant membranes or coatings with tuneable hierarchy, stiffness, and hardness. Our study represents a potential strategy for complex materials design that may open opportunities for hard tissue repair and provide insights into the role of molecular disorder in human physiology and pathology.
Osteosarcoma (OS) is the most common primary malignant tumor of the bone. Due to its high heterogeneity and to survival signals from bone microenvironment, OS can resist to standard treatments, ...therefore novel therapies are needed. c-MET oncogene, a tyrosine-kinase receptor, plays a crucial role in OS initiation and progression. The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment. We tested different doses of CBZ in in vitro models of OS alone or in co-culture with bone cells in order to reproduce OS-tumor microenvironment interactions. CBZ is able to decrease proliferation and migration of OS cells, inhibiting ERK and AKT signaling pathways. Furthermore, CBZ leads to the inhibition of the proliferation of OS cells expressing receptor activator of nuclear factor κB (RANK), due to its effect on bone microenvironment, where it causes an overproduction of osteoprotegerin and a decrease of production of RANK ligand by osteoblasts. Overall, our data demonstrate that CBZ might represent a new potential treatment against OS, affecting both OS cells and their microenvironment. In this scenario, RANK expression in OS cells could represent a predictive factor of better response to CBZ treatment.
Abstract Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to ...distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei , Albatrellus confluens , Cordyceps militaris , Ganoderma lucidum , Poria cocos and Silybum marianum , together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.
Ultrathin polymeric films have recently attracted tremendous interest as functional components of coatings, separation membranes, and sensors, with applications spanning from environment-related ...processes to soft robotics and wearable devices. In order to support the development of robust devices with advanced performances, it is necessary to achieve a deep comprehension of the mechanical properties of ultrathin polymeric films, which can be significantly affected by confinement effects at the nanoscale. In this review paper, we collect the most recent advances in the development of ultrathin organic membranes with emphasis on the relationship between their structure and mechanical properties. We provide the reader with a critical overview of the main approaches for the preparation of ultrathin polymeric films, the methodologies for the investigation of their mechanical properties, and models to understand the primary effects that impact their mechanical response, followed by a discussion on the current trends for designing mechanically robust organic membranes.
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Organic chemistry; Membranes; Engineering
The design, analysis, fabrication, and characterization of two distinct MEMS rotational structures are provided; these structures include a classical symmetrical lancet structure and a novel ...symmetrical C-shaped structure provided with a tilted arm, and both are actuated by thermal actuators. Our proposed C-shaped structure implemented a curved beam mechanism to enhance the movement delivered by the thermal actuators. The geometrical parameters of our proposed device were optimized using the design of experiment (DOE) method. Furthermore, the analytical modeling based on Castigliano's second theorem and the simulations based on the finite element method (FEM) were used to predict the behavior of the symmetrical C-shaped structure; the results were in good agreement with each other. The MEMS-based rotational structures were fabricated on silicon-on-insulator (SOI) wafers using bulk micromachining technology and deep reactive ion etching (DRIE) processes. The fabricated devices underwent experimental characterization; our results showed that our proposed MEMS rotational structure exhibited a 28% improvement in the delivered displacement compared to the symmetrical lancet structure. Furthermore, the experimental results showed good agreement with those obtained from numerical analysis. Our proposed structures have potential applications in a variety of MEMS devices, including accelerometers, gyroscopes, and resonators, due to their ability to maximize displacement and thus enhance sensitivity.
Microgrippers are promising tools for micro-manipulation and characterization of cells. In this paper, a biocompatible electro-thermally actuated microgripper with rotary capacitive position sensor ...is presented. To overcome the limited displacement possibilities usually provided by electrothermal actuators and to achieve the desired tweezers output displacement, conjugate surface flexure hinges (CSFH) are adopted. The microgripper herein reported can in principle manipulate biological samples in the size range between 15 and 120 µm. A kinematics modeling approach based on the pseudo-rigid-body-method (PRBM) is applied to describe the microgripper’s working mechanism, and analytical modeling, based on finite elements method (FEM), is used to optimize the electrothermal actuator design and the heat dissipation mechanism. Finally, FEM-based simulations are carried out to verify the microgripper, the electrothermal actuator and heat dissipation mechanism performance, and to assess the validity of the analytical modeling.
Hybrid nanomaterials fabricated by the heterogeneous integration of 1D (carbon nanotubes) and 2D (graphene oxide) nanomaterials showed synergy in electrical and mechanical properties. Here, we ...reported the infiltration of carboxylic functionalized single-walled carbon nanotubes (C-SWNT) into free-standing graphene oxide (GO) paper for better electrical and mechanical properties than native GO. The stacking arrangement of GO sheets and its alteration in the presence of C-SWNT were comprehensively explored through scanning electron microscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction. The C-SWNTs bridges between different GO sheets produce a pathway for the flow of electrical charges and provide a tougher hybrid system. The nanoscopic surface potential map reveals a higher work function of the individual functionalised SWNTs than surrounded GO sheets showing efficient charge exchange. We observed the enhanced conductivity up to 50 times and capacitance up to 3.5 times of the hybrid structure than the GO-paper. The laminate of polystyrene composites provided higher elastic modulus and mechanical strength when hybrid paper is used, thus paving the way for the exploitation of hybrid filler formulation in designing polymer composites.
Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous ...metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1
carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases.
A review on the mechanical characterization of materials at small length scale is presented. The focus is on the different micro- and nanoscale testing techniques, the variety of materials ...investigated by the scientific and industrial communities and the mechanical quantities identified by such methodologies.
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