National Research Center for Rehabilitation Technical Aids

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

The emergence of aggregation-induced emission luminogens (AIEgens) has significantly stimulated the development of luminescent supramolecular materials because their strong emissions in the aggregated state have resolved the notorious obstacle of the aggregation-caused quenching (ACQ) effect, thereby enabling AIEgen-based supramolecular materials to have a promising prospect in the fields of luminescent materials, sensors, bioimaging, drug delivery, and theranostics. Moreover, in contrast to conventional fluorescent molecules, the configuration of AIEgens is highly twisted in space. Investigating AIEgens and the corresponding supramolecular materials provides fundamental insights into the self-assembly of nonplanar molecules, drastically expands the building blocks of supramolecular materials, and pushes forward the frontiers of supramolecular chemistry. In this review, we will summarize the basic concepts, seminal studies, recent trends, and perspectives in the construction and applications of AIEgen-based supramolecular materials with the hope to inspire more interest and additional ideas from researchers and further advance the development of supramolecular chemistry.

Soft wearable electronics for underwater applications are of interest, but depend on the development of a waterproof, long-term sustainable power source. In this work, we report a bionic stretchable nanogenerator for underwater energy harvesting that mimics the structure of ion channels on the cytomembrane of electrocyte in an electric eel. Combining the effects of triboelectrification caused by flowing liquid and principles of electrostatic induction, the bionic stretchable nanogenerator can harvest mechanical energy from human motion underwater and output an open-circuit voltage over 10 V. Underwater applications of a bionic stretchable nanogenerator have also been demonstrated, such as human body multi-position motion monitoring and an undersea rescue system. The advantages of excellent flexibility, stretchability, outstanding tensile fatigue resistance (over 50,000 times) and underwater performance make the bionic stretchable nanogenerator a promising sustainable power source for the soft wearable electronics used underwater.

The synthesis of water-soluble near-infrared (NIR)-emissive fluorescent molecules with aggregation-induced emission (AIE) characteristics and theranostic functions is highly desirable but remains challenging. In this work, we designed and readily prepared for the first time such a molecule with AIE features, good water-solubility and intense emission in the NIR region. This AIE luminogen (AIEgen) is able to specifically "light up" the cell membrane without the involvement of a washing procedure. Interestingly, the staining process can be performed by simply shaking the culture with cells at room temperature for only a few seconds after the addition of the AIEgen, indicating an ultrafast and easy-to-operate staining protocol. This is the first fluorescent "light-up" probe for cell-imaging that allows the combination of a short staining period (at the second-level) with a wash-free process. Additionally, the presented AIEgen has also been developed to serve as an excellent phototherapeutic agent for high efficiency generation of reactive oxygen species (ROS) upon visible light irradiation, which allows its effective application in the photodynamic ablation of cancer cells, demonstrating its dual role as an imaging and phototherapeutic agent.

Hydrogel, as a good cartilage tissue-engineered scaffold, not only has to possess robust mechanical property but also has to have an intrinsic self-healing property to integrate itself or the surrounding host cartilage. In this work a double cross-linked network (DN) was designed and prepared by combining Diels-Alder click reaction and acylhydrazone bond. The DA reaction maintained the hydrogel's structural integrity and mechanical strength in physiological environment, while the dynamic covalent acylhydrazone bond resulted in hydrogel's self-healing property and controlled the on-off switch of network cross-link density. At the same time, the aldehyde groups contained in hydrogel further promote good integration of the hydrogel to surrounding tissue based on aldehyde-amine Schiff-base reaction. This kind of hydrogel has good structural integrity, autonomous self-healing, and tissue-adhesive property and simultaneously will have a good application in tissue engineering and tissue repair field.

This retrospective cohort study investigated whether particular antiretroviral agents are associated with a higher risk for developing grade 4 liver enzyme elevations (LEEs) in patients with human immunodeficiency virus (HIV) type 1 infection who are starting to receive highly active antiretroviral therapy (HAART). Grade 4 LEE was defined as aminotransferase levels >10 times the upper limit of normal and >200 U above baseline levels. A multivariate Cox model was used to identify risk factors. The incidence of LEE was 6.3%. No patients died of LEE consequences. Risk factors were higher baseline alanine aminotransferase levels, chronic hepatitis B or C virus infection, antiretroviral therapy-naive patients undergoing their first HAART regimen, recent start of a regimen of nevirapine or high-dose ritonavir, and female sex. In hepatitis B virus (HBV)-coinfected patients, discontinuing lamivudine (3TC) use was a risk factor. In 97% of cases, >or=1 risk factor was present. In HBV-coinfected patients using 3TC, continued use of 3TC should be considered, even if 3TC-resistant HIV strains develop.

Abstract Changes in endocardial pressure (EP) have important clinical significance for heart failure patients with impaired cardiac function. As a vital parameter for evaluating cardiac function, EP is commonly monitored by invasive and expensive cardiac catheterization, which is not feasible for long‐term and continuous data collection. In this work, a miniaturized, flexible, and self‐powered endocardial pressure sensor (SEPS) based on triboelectric nanogenerator (TENG), which is integrated with a surgical catheter for minimally invasive implantation, is reported. In a porcine model, SEPS is implanted into the left ventricle and the left atrium. The SEPS has a good response both in low‐ and high‐pressure environments. The SEPS achieves the ultrasensitivity, real‐time monitoring, and mechanical stability in vivo. An excellent linearity ( R 2 = 0.997) with a sensitivity of 1.195 mV mmHg −1 is obtained. Furthermore, cardiac arrhythmias such as ventricular fibrillation and ventricular premature contraction can also be detected by SEPS. The device may promote the development of miniature implantable medical sensors for monitoring and diagnosis of cardiovascular diseases.

ConspectusOver the past few decades, cancer nanomedicine has been under intensive development for applications in drug delivery, cancer therapy, and molecular imaging. However, there exist a series of complex biological barriers in the path of a nanomedicine from the site of administration to the site of action. These barriers considerably prevent a nanomedicine from reaching its targets in a sufficient concentration and thus severely limit its therapeutic benefits. According to the delivery process, these biological delivery barriers can be briefly summarized in the following order: blood circulation, tumor accumulation, tumor penetration, cellular internalization, and intracellular drug release. The therapeutic effect of a nanomedicine is strongly determined by its ability to overcome these barriers. However, advances in cancer biology have revealed that each barrier has its own distinct microenvironment, which imposes different requirements on the optimal design of nanocarriers, thus further complicating the delivery process. For example, the pH of blood is neutral, while the tumor extracellular environment features an acidic pH (pHe ≈ 6.5–7.0) and the endosome and lysosome are more acidic (pH 5.5–4.5). The nanoparticles (NPs) should be able to change their properties to adapt to each individual environment for robust and effective delivery. This demand promotes the design and development of smart delivery carriers that can respond to endogenous and exogenous stimuli.It is well-documented that tumors develop acidic extracellular microenvironments with pH ≈ 6.5–7.0 due to their abnormal metabolism in comparison with normal tissues. This provides a unique tool for designing smart NP drug delivery systems. Our studies have revealed that the NPs’ physiochemical properties, such as particle size and surface charge, have profound effects on their systemic transport in the body. In different delivery stages, the NPs should possess different sizes or surface charges for optimal performance. We developed a class of stimuli-responsive NPs by incorporating tumor-acidity-cleavable maleic acid amide (TACMAA) as a design feature. TACMAA is produced by the facile reaction of an amino group with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives and can be cleaved under tumor acidity. By virtue of such characteristics, NPs containing TACMAA enable size or surface charge switching at tumor sites so that they can overcome those delivery barriers for improved drug delivery and cancer therapy. In this Account, we systemically review the development and evolution of TACMAA-based delivery systems and elaborate how TACMAA helps the innovation and design of intelligent nanocarriers for overcoming the delivery barriers. In particular, our Account focuses on five parts: TACMAA chemistry, tumor-acidity-triggered charge reversal, tumor-acidity-triggered shell detachment, tumor-acidity-triggered size transition, and tumor-acidity-triggered ligand reactivation. We provide detailed information on how tumor-acidity-triggered property changes correlate with the ability of NPs to overcome delivery barriers.

Motor performance is improved by stimulation of the agonist muscle during movement. However, related brain mechanisms remain unknown. In this work, we perform a functional magnetic resonance imaging study in 21 healthy subjects under three different conditions: (1) movement of right ankle alone, (2) movement and simultaneous stimulation of the agonist muscle or (3) movement and simultaneous stimulation of a control area. We constructed weighted brain networks for each condition by using functional connectivity. Network features were analyzed using graph theoretical approaches. We found that (1) the second condition evokes the strongest and most widespread brain activations (5147 versus 4419 and 2320 activated voxels); and (2) this condition also induces a unique network layout and changes hubs and the modular structure of the brain motor network by activating the most “silent” links between primary somatosensory centers and the motor cortex, particularly weak links from the thalamus to the left primary motor cortex. Significant statistical differences were found when the strength values of the right cerebellum (P<0.001) or the left thalamus (P=0.006) were compared among the three conditions. Over the years, studies reported a small number of projections from the thalamus to the motor cortex. This is the first work to present functions of these pathways. These findings reveal mechanisms for enhancing motor function with somatosensory stimulation, and suggest that network function cannot be thoroughly understood when weak ties are disregarded.

Nanoparticles (NPs) have emerged as an effective means to deliver therapeutic drugs for cancer treatment, as they can preferentially accumulate at tumor site through the enhanced permeability and retention effect. Various forms of NPs including liposomes, polymeric micelles, and inorganic particles have been used for therapeutic applications. However, the therapeutic benefits of nanomedicines are suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumor penetration can be a vital obstacle. Tumor develops characteristic pathological environment, such as abnormal vasculature, elevated interstitial fluid pressure, and dense extracellular matrix, which intrinsically hinder the transport of nanomedicines in the tumor parenchyma. The physicochemical properties of the NPs such as size, shape, and surface charge have profound effect on tumor penetration. In this review, we will highlight the factors that affect the transport of NPs in solid tumor, and then elaborate on designing strategies to improve NPs' penetration and uniform distribution inside the tumor interstitium. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Luminogens with aggregation-induced emission (AIEgens) characteristics have been well developed and applied in various areas such as bio-imaging, theranostics, organic photoelectronics and chemo/bio sensors. However, most of the reported AIEgens suffer from the disadvantages of complex organic synthesis and high cost, as well as being environmentally unfriendly and hard to degrade, which have largely limited their real applications. In this work, we discovered berberine chloride, a natural isoquinoline alkaloid isolated from Chinese herbal plants, as an unconventional rotor-free AIEgen with bright solid-state emission and water-soluble characteristics. Single crystal structure analysis and optical property, viscosity, and host-guest interaction studies suggested that intramolecular vibration and twisted intramolecular charge transfer were responsible for the AIE phenomenon of berberine chloride. Moreover, berberine chloride was biocompatible and could specifically target lipid droplets in a fluorescence turn-on and wash-free manner, demonstrating the great potential of natural products as promising AIE probes.

This review outlines the fabrication methods and bioimaging applications of the fluorescent nanoparticles based on AIE luminogens (AIE dots).

Cancer is the leading cause of death worldwide. With the advantages of low cost, high sensitivity and ease of accessibility, fluorescence imaging has been widely used for cancer detection in the scientific field. Aggregation-induced emission luminogens (AIEgens) are a class of synthesized fluorescent probes with high brightness and photostability in the aggregate state. Herein, a new positively-charged AIEgen, abbreviated as TPE-IQ-2O, is designed and characterized. TPE-IQ-2O not only can distinguish cancer cells from normal cells with high contrast with the aid of the difference in mitochondrial membrane potential as well as the quantity of mitochondria, but it also works as a promising photosensitizer to kill cancer cells through generation of reactive oxygen species upon white light irradiation, thus making it a promising AIE theranostic system.

The ATDC5 cell line is derived from mouse teratocarcinoma cells and characterized as a chondrogenic cell line which goes through a sequential process analogy to chondrocyte differentiation. Thus, it is regarded as a promising in vitro model to study the factors that influence cell behaviors during chondrogenesis. It also provides insights in exploring signaling pathways related to skeletal development as well as interactions with innovative materials. To date, over 200 studies have utilized ATDC5 to obtain lots of significant findings. In this review, we summarized the literature of ATDC5 related studies and emphasized the application of ATDC5 in chondrogenesis. In addition, the general introduction of ATDC5 including its derivation and characterization is covered in this article.

Non-aromatic peptides fluoresce under pressure.

formation of intermediate or rotation around the elongated C[double bond, length as m-dash]C bond, is responsible for the AIE effect, which is strongly structure-dependent but not related to structural rigidity.

) was successfully applied in the detection of Cd(ii) in aqueous solution at neutral pH, and showed a 500-fold fluorescence "turn-on" response to Cd(ii) with good selectivity.

Microgel assembly, a macroscopic aggregate formed by bottom-up assembly of microgels, is now emerging as prospective biomaterials for applications in tissue engineering and regenerative medicine (TERM). This mini-review first summarizes the fabrication strategies available for microgel assembly, including chemical reaction, physical reaction, cell-cell interaction and external driving force, then highlights its unique characteristics, such as microporosity, injectability and heterogeneity, and finally itemizes its applications in the fields of cell culture, tissue regeneration and biofabrication, especially 3D printing. The problems to be addressed for further applications of microgel assembly are also discussed.

Host immune response induced by foreign bone biomaterials plays an important role in determining their fate after implantation. Hence, it is well worth designing advanced bone substitute materials with beneficial immunomodulatory properties to modulate the host-material interactions. Bioactive glasses (BG), with excellent osteoconductivity and osteoinductivity, are regarded as important biomaterials in the field of bone regeneration. In order to explore a novel BG-based osteoimmunomodulatory implant with the capacity of potentially enhancing bone regeneration, it is a possible way to regulate the local immune microenvironment through manipulating macrophage polarization. In this study, strontium-substituted submicrometer bioactive glass (Sr-SBG) was prepared as an osteoimmunomodulatory bone repair material. To investigate whether the incorporation of Sr into SBG could synergistically improve osteogenesis by altering macrophage response, we systematically evaluated the interaction between Sr-SBG and macrophage during the process of bone regeneration by in vitro biological evaluation and in vivo histological assessment. It was found that the Sr-SBG modulates proper inflammatory status, leading to enhanced osteogenesis of mouse mesenchymal stem cells (mMSCs) and suppressed osteoclastogenesis of RAW 264.7 cells compared to SBG without strontium substitution. In vivo study confirmed that Sr-SBG initiated a less severe immune response and had an improved effect on bone regeneration than SBG, which corresponded with the in vitro evaluation. In conclusion, these findings suggested that Sr-SBG could be a promising immunomodulatory bone repair material designed for improved bone regeneration.

Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ-945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while the small particles carrying Pt-prodrug enable deep tumor penetration as well as intracellularly specific drug release to kill more cancer cells. Our studies demonstrate that BLZ-945SCNs/Pt outperform their monotherapy counterparts in multiple tumor models. The underlying mechanism studies suggest that the designer pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but also modulates the tumor immune environment to eventually augment the antitumor effect of CD8+ cytotoxic T cells through TAMs depletion.