Temperature is a key parameter to regulate cell function, and biochemical reactions inside a cell in turn affect the intracellular temperature. It's vitally necessary to measure cellular temperature ...to provide sufficient information to fully understand life science, while the conventional methods are incompetent. Over the last decade, many ingenious thermometers have been developed with the help of nanotechnology, and real‐time intracellular temperature measurement at the micro/nanoscale has been realized with high temporal‐spatial resolution. With the help of these techniques, several mechanisms of thermogenesis inside cells have been investigated, even in subcellular organelles. Here, current developments in cellular thermometers are highlighted, and a picture of their applications in cell biology is presented. In particular, temperature measurement principle, thermometer design and latest achievements are also introduced. Finally, the existing opportunities and challenges in this ongoing field are discussed.
Cellular thermometers flourished in the last decade under the inspiration of exploring the mechanisms of cell activities through intracellular temperature. Various strategies based on nanotechnology have been proposed to realize real‐time intracellular temperature measurements with high temporal‐spatial resolution. A comprehensive review of the recent achievements, existing challenges, and future prospects of cellular thermometers is provided.
With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive ...characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications.
Building Information Modelling (BIM) is one of the important areas in current Virtual Reality (VR) research. VR research considers not only the technological development, a very important part of the ...research also concerns the application of the technologies and their adoption by the practices. This paper firstly presents an analysis of the current state of BIM in the Architecture, Engineering and Construction (AEC) industry and a re-assessment of its role and potential contribution in the near future. The paper analyses the readiness of the industry with respect to the (1) product, (2) processes and (3) people, to position BIM adoption in terms of current status and expectations across disciplines. The findings indicate that there were both technical and non-technical issues that need consideration. The evidence also suggests that there are varying levels of adoption and therefore the need for a specific tool to facilitate BIM adoption. The study revealed that even the market leaders who are early technology adopters in the Australian industry in many cases have varying degrees of practical experiential knowledge of BIM and hence at times different understandings and different levels of confidence regarding the future diffusion of BIM technology throughout the industry. There have been numerous factors affecting BIM adoption, which can be grouped into two main areas: technical tool functional requirements and needs, and non-technical strategic issues. There are varying levels of adoption and understanding within countries — from discipline to discipline and client to client. There are also varying levels of adoption from country to country and although many researchers and practitioners espouse collaborative working environments there are still challenges to be met in many parts of the world, particularly, in relation to a fully integrated collaborative multidisciplinary mode of operation. The challenges for the research community lie not only in addressing the technical solutions or addressing human centred issues but it is also in creating the enabling environment of a decision framework, which integrates both the technical and non-technical challenges. The need for guidance on where to start, what tools are available and how to work through the legal, procurement and cultural challenges was evidenced in the exploratory study. Therefore the Collaborative BIM Decision Framework has been initiated to facilitate the BIM adoption in the AEC industry, based upon these industry concerns, which consists of four interrelated key elements. The findings are drawn from a major research project funded by the Australian Cooperative Research Centre for Construction Innovation (CRC-CI), with a focus on the Australian context.
► BIM adoption needs consideration of both technical tool functional requirements and non-technical strategic issues. ► The Collaborative BIM Decision Framework is initiated to support the facilitation of the BIM adoption in the AEC industry.
With unique physicochemical properties and biological effects, magnetic nanomaterials (MNMs) play a crucial role in the biomedical field. In particular, magnetic iron oxide nanoparticles (MIONPs) are ...approved by the United States Food and Drug Administration (FDA) for clinical applications at present due to their low toxicity, biocompatibility, and biodegradability. Despite the unarguable effectiveness, massive space for improving such materials’ performance still needs to be filled. Recently, many efforts have been devoted to improving the preparation methods based on the materials’ biosafety. Besides, researchers have successfully regulated the performance of magnetic nanoparticles (MNPs) by changing their sizes, morphologies, compositions; or by aggregating as-synthesized MNPs in an orderly arrangement to meet various clinical requirements. The rise of cloud computing and artificial intelligence techniques provides novel ways for fast material characterization, automated data analysis, and mechanism demonstration. In this review, we summarized the studies that focused on the preparation routes and performance regulations of high-quality MNPs, and their special properties applied in biomedical detection, diagnosis, and treatment. At the same time, the future development of MNMs was also discussed.
Nanoparticle-mediated tumor magnetic induction hyperthermia has received tremendous attention. However, it has been a challenge to improve the efficacy at 42 °C therapeutic temperatures without ...resistance to induced thermal stress. Therefore, we designed a magnetic hydrogel nanozyme (MHZ) utilizing inclusion complexation between PEGylated nanoparticles and α-cyclodextrin, which can enhance tumor oxidative stress levels by generating reactive oxygen species through nanozyme-catalyzed reactions based on tumor magnetic hyperthermia. MHZ can be injected and diffused into the tumor tissue due to shear thinning as well as magnetocaloric phase transition properties, and magnetic heat generated by the Fe3O4 first gives 42 °C of hyperthermia to the tumor. Fe3O4 nanozyme exerts peroxidase-like properties in the acidic environment of tumor to generate hydroxyl radicals (•OH) by the Fenton reaction. The hyperthermia promotes the enzymatic activity of Fe3O4 nanozyme to produce more •OH. Simultaneously, •OH further damages the protective heat shock protein 70, which is highly expressed in hyperthermia to enhance the therapeutic effect of hyperthermia. This single magnetic nanoparticle exerts dual functions of hyperthermia and catalytic therapy to synergistically treat tumors, overcoming the resistance of tumor cells to induced thermal stress without causing severe side effects to normal tissues at 42 °C hyperthermia.
Early diagnosis and treatment of acute ischemic stroke poses a significant challenge due to its suddenness and short therapeutic time window. Human endogenous cells derived biomimetic drug carriers ...have provided new options for stroke theranostics since these cells have higher biosafety and targeting abilities than artificial carriers. Inspired by natural platelets (PLTs) and their role in targeting adhesion to the damaged blood vessel during thrombus formation, we fabricated a biomimetic nanocarrier comprising a PLT membrane envelope loaded with l-arginine and γ-Fe2O3 magnetic nanoparticles (PAMNs) for thrombus-targeted delivery of l-arginine and in situ generation of nitric oxide (NO). Results demonstrate that the engineered 200 nm PAMNs inherit the natural properties of the PLT membrane and achieve rapid targeting to ischemic stroke lesions under the guidance of an external magnetic field. Subsequent to the release of l-arginine at the thrombus site, endothelial cells produce NO, which promotes vasodilation to disrupt the local PLT aggregation. Rapid targeting of PAMNs to stroke lesions as well as in situ generation of NO prompts vasodilation, recovery of blood flow, and reperfusion of the stroke microvascular. Thus, these PLT membrane derived nanocarriers are diagnostically beneficial for localizing stroke lesions and a promising modality for executing therapies.
More and more studies have demonstrated that proteasomal degradation occurs in the development of various diseases, including ventricular remodeling, which is a cardiac pathological change and ...seriously makes patient outcomes worse. Our preliminary results showed that Guanxin V, an effective and safe complementary and alternative medicine for ventricular remodeling, reverses ventricular hypertrophy by transforming growth factor-beta 1 (TGF-β1), but the specific mechanism needs to be explored. The left anterior descending coronary artery was ligated to build a ventricular remodeling model. Cardiac function and histopathology were measured. Fibrosis-related indicators were detected. Moreover, cardiomyocytes were exposed to hydrogen peroxide to construct an in vitro model of ventricular remodeling. The stability of the Vimentin protein was assessed with cycloheximide and MG132. Endogenous and exogenous TGF-β1-Vimentin interactions were detected by co-immunoprecipitation. Guanxin V significantly eased heart function and improved fibrosis in ventricular remodeling. Mechanistically, Guanxin V promoted TGF-β1-mediated proteasomal degradation of Vimentin and reduced the TGF-β1-Vimentin interaction. Here, we reported a completely new mechanism, Guanxin V alleviates ventricular remodeling by promoting and targeting TGF-β1-mediated proteasomal degradation of Vimentin, which provides a new target for the management of ventricular remodeling and lays the foundation for the further clinical promotion of Guanxin V.
Abstract
As pioneering Fe
3
O
4
nanozymes, their explicit peroxidase (POD)-like catalytic mechanism remains elusive. Although many studies have proposed surface Fe
2+
-induced Fenton-like reactions ...accounting for their POD-like activity, few have focused on the internal atomic changes and their contribution to the catalytic reaction. Here we report that Fe
2+
within Fe
3
O
4
can transfer electrons to the surface via the Fe
2+
-O-Fe
3+
chain, regenerating the surface Fe
2+
and enabling a sustained POD-like catalytic reaction. This process usually occurs with the outward migration of excess oxidized Fe
3+
from the lattice, which is a rate-limiting step. After prolonged catalysis, Fe
3
O
4
nanozymes suffer the phase transformation to γ-Fe
2
O
3
with depletable POD-like activity. This self-depleting characteristic of nanozymes with internal atoms involved in electron transfer and ion migration is well validated on lithium iron phosphate nanoparticles. We reveal a neglected issue concerning the necessity of considering both surface and internal atoms when designing, modulating, and applying nanozymes.
Nanobubbles (NBs), given its extraordinary properties, have drawn keen attention in the field of nanotechnology worldwide. However, compared to that of surface NBs, generation of stable bulk NBs ...remains an arduous task with the prevailing method. In this study, we developed a pressure-driven method to prepare bulk NBs by repeatedly compressing sulfur hexafluoride (SF6) gas into water. The results show that NBs with a mean diameter of 240 ± 9 nm and a polydispersity index of 0.25 were successfully prepared. The generated NBs had a high negative zeta potential (−40 ± 2 mV) with stability of more than 48 h. Under the condition of 600 times repeated compression, the NB concentration could reach about 1.92 × 1010 bubbles/mL. Furthermore, we examine the possible formation mechanism involved in NB generation by virtue of optical microscopy and attenuated total reflectance Fourier transform infrared (ATR–FTIR) spectroscopy. The microscopic results showed that microbubbles about 10–50 μm formed first and then decreased to be nanoscale-sized. A stronger hydrogen bond was detected by ATR–FTIR spectroscopy during the shrinking of microbubbles into NBs. It is speculated that the disappearance of microbubbles contributes to the formation of NBs, and the strong hydrogen bond at the gas–water interface prompts the stability of NBs. Therefore, repeated compression of the gas in aqueous solution could be a new method to prepare stable nanosized bubbles for wide applications in the future.
The interactions between charged nanoparticles (NPs) and charge-neutral phospholipid membranes are investigated by coarse-grained molecular dynamics simulations. Three kinds of nanoparticles are ...modeled with different surface charge densities: the uncharged one, the positively charged one, and the negatively charged one. We find that the electrostatic attraction improves the adhesion of a charged nanoparticle to the membrane. With the increase of electrostatic energy, a charged NP can be almost fully wrapped by the membrane. In addition, analyses of structural variations suggest that the adhesion of a charged NP induces a local transition in fluid bilayers. Some thermodynamic quantities such as free energy, entropy, and enthalpy are also obtained to explain the process of NPs binding. Furthermore, the bending energy of wrapping of NPs against the electrostatic potential energy is also discussed based on the Helfrich theory, indicating that the driving force of the wrap originates from the gain in electrostatic energy at the cost of the elastic energy of biomembranes. Our observations shed light on the origin of experiments of the wrap as well as the mechanism of structural transitions of membranes due to the electrostatic binding.
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