Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the ...effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.
Soft dielectric elastomer actuators (DEAs) exhibit interesting muscle-like behavior for the development of soft robots. However, it is challenging to model these soft actuators due to their material ...nonlinearity, nonlinear electromechanical coupling, and time-dependent viscoelastic behavior. Most recent studies on DEAs focus on issues of mechanics, physics, and material science, while much less importance is given to quantitative characterization of DEAs. In this paper, we present a detailed experimental investigation probing the voltage-induced electromechanical response of a soft DEA that is subjected to cyclic loading and propose a general constitutive modeling approach to characterize the time-dependent response, based on the principles of nonequilibrium thermodynamics. In this paper, some of the key observations are found as follows: 1) Creep exhibits the drift phenomenon, and is dominant during the first three cycles. The creep decreases over time and becomes less dominant after the first few cycles; 2) a significant amount of hysteresis is observed during all cycles and it becomes repeatable after the first few cycles; 3) the peak of the displacement is shifted from the peak of the voltage signal and occurs after it. To account for these viscoelastic phenomena, a constitutive model is developed by employing several dissipative nonequilibrium mechanisms. The quantitative comparisons of the experimental and simulation results demonstrate the effectiveness of the developed model. This modeling approach can be useful for control of a viscoelastic DEA and paves the way to emerging applications of soft robots.
Reactive oxygen species (ROS)‐based cancer therapy, such as photodynamic therapy (PDT), is subject to the hypoxia and overexpressed glutathione (GSH) found in the tumor microenvironment (TME). ...Herein, a novel strategy is reported to continuously and simultaneously regulate tumor hypoxia and reducibility in order to achieve the desired therapeutic effect. To accomplish this, a biocompatible nanoplatform (MnFe2O4@metal–organic framework (MOF)) is developed by integrating a coating of porphyrin‐based MOF as the photosensitizer and manganese ferrite nanoparticle (MnFe2O4) as the nanoenzyme. The synthetic MnFe2O4@MOF nanoplatform exhibits both catalase‐like and glutathione peroxidase‐like activities. Once internalized in the tumor, the nanoplatform can continuously catalyze H2O2 to produce O2 to overcome the tumor hypoxia by cyclic Fenton reaction. Meanwhile, combined with the Fenton reaction, MnFe2O4@MOF is able to persistently consume GSH in the presence of H2O2, which decreases the depletion of ROS upon laser irradiation during PDT and achieves better therapeutic efficacy in vitro and in vivo. Moreover, the nanoplatform integrates a treatment modality with magnetic resonance imaging, along with persistent regulation of TME, to promote more precise and effective treatment for future clinical application.
A hydrogen peroxide (H2O2)‐responsive MnFe2O4@MOF nanostructure with continuous auto‐generating oxygen and meanwhile decreasing glutathione capacity in the tumor microenvironment (TME) is developed for enhancing the photodynamic therapy antitumor therapeutic effect. This multifunctional nanoplatform integrating treatment and imaging, along with continuous modulation of TME, could promote more precise and effective treatment in future clinical applications.
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After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local ...multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo. In addition, the drug concentrations on the periphery tissues of defect are maintained above INH/RFP minimal inhibitory concentrations even up to 12weeks post-surgery, while they are extremely low in blood. Examinations of certain serum enzymes suggest no harm to hepatic or renal functions. Micro-CT evaluations and histology results also indicate partly degradation of the composite scaffolds and new bone growth in the cavity. These results suggest promising applications of our hierarchical composite scaffold in bone regeneration and local anti-TB therapy after osteoarticular TB debridement surgery.
Since the last two decades, many researchers have refocused on using natural fibres, as reinforcements for cementitious and polymer based structural materials. The use of natural fibres for ...structural applications is not modern. Long before a century ago people in many small towns in China and Korea already mixed straws with mud to build walls in villages. However, at that time there was no systematic way to study the fundamental mechanism and interpret how natural fibres strengthen structures and what processes should be adopted to maximize the performance of natural materials. Currently, nevertheless natural fibre reinforced polymer (NFRP) composites have been widely used in automotive and building industries, it is still a room to promote them to high-level structural applications like primary structural components of aerospace and maritime structures. It is difficult to evaluate the quality of natural fibres, which generally extracted from the nature, and thus it is challenging to develop a generic formula to predict the structural and mechanical properties of NFRP composites. Hydrophilic and hydrophobic properties of natural fibres and polymers, respectively, cause poor bonding interaction at interface. Traditional shear-lag model was popularly used to study the stress transfer mechanism between fibre and matrix of advanced composites. However, such model is not applicable to NFRP composites due to the imperfect shape of nature fibres along their longitudinal direction and irregular shape of fibres' cross section. In this paper, analysis on different aspects in related to the use of natural fibres for real life engineering applications is given. Basic analytical models focusing on the stress transferability in composites are also discussed to provide an insight for researchers and engineers to understand the design and requirements of using natural fibres for structural applications in the future.
Sodium borohydride (NaBH4) is among the most studied hydrogen storage materials because it is able to deliver high‐purity H2 at room temperature with controllable kinetics via hydrolysis; however, ...its regeneration from the hydrolytic product has been challenging. Now, a facile method is reported to regenerate NaBH4 with high yield and low costs. The hydrolytic product NaBO2 in aqueous solution reacts with CO2, forming Na2B4O7⋅10 H2O and Na2CO3, both of which are ball‐milled with Mg under ambient conditions to form NaBH4 in high yield (close to 80 %). Compared with previous studies, this approach avoids expensive reducing agents such as MgH2, bypasses the energy‐intensive dehydration procedure to remove water from Na2B4O7⋅10 H2O, and does not require high‐pressure H2 gas, therefore leading to much reduced costs. This method is expected to effectively close the loop of NaBH4 regeneration and hydrolysis, enabling a wide deployment of NaBH4 for hydrogen storage.
Coming full circle: A facile method to regenerate NaBH4 with high yield and low cost from its hydrolytic product NaBO2 is presented. This method effectively closes the loop of NaBH4 hydrolysis and regeneration and therefore enables a wide deployment of NaBH4 for hydrogen storage.
Energy storage materials are vital to the use of clean energy such as hydrogen and electrochemical energy. This paper reviews the recent progress on the application of dielectric barrier discharge ...plasma-assisted milling (P-milling), a new material synthesis method developed by ourselves, in preparing energy storage materials including Mg-based hydrogen storage materials and anode materials for lithium-ion batteries. We discuss in particular the advantages of this novel milling technique on preparing those materials and improving their energy storage performances. For Mg-based hydrogen storage materials, P-milling can realize the simultaneous rapid formation of a Mg-based solid solution and the in-situ induced catalyst MgF2, thus realizing the dual tuning of thermodynamic and kinetic properties. For anode materials of lithium-ion batteries, core-shell structures are easily formed by P-milling, and those prepared materials show higher capacities and cycling stability in comparison to those prepared by conventional ball milling (C-milling). P-milling offers a simple, cost effective and pollution-free way for preparing nano-materials or accelerating mechanochemical reactions, paving the way for large scale production of energy storage materials in the future.
•Dielectric barrier discharge plasma-assisted milling (P-milling) was developed.•P-milling was adopted to synthesize energy storage materials.•Dual tuning of the thermodynamic and kinetic properties of MgH2 is realized.•Anode materials with higher capacities and cycling stability are obtained.•P-milling is promising for large-scale industrial production.
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