Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and ...bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native‐bone‐like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical‐sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica‐functionalized scaffolds can be implanted via a cell/GF‐free, one‐step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects.
A biosilicification strategy is developed to provide a uniform and robust osteoinductive surface on porous natural collagen scaffolds. The resultant nanosilica–collagen (nSC) scaffolds possess topographical and chemical cues for superior in situ bone defect repair, without the use of exogenous cells or growth factors. This novel preparation of biomimetic bone scaffolds shows promising clinical applications in the treatment of bone defects.
The new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor ...by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted “CellPhoneDB” analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.
•ACE2 is expressed in lung, liver, stomach, ileum, kidney and colon.•ANPEP, DPP4 and ENPEP were identified as the candidate co-receptors, showing the most similar expression patterns with ACE2.•Macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling.
At a microscopic scale, the failure of brittle materials results from crack initiation, propagation and coalescence. Acoustic emission (AE) technique, especially parameter analysis, has been widely ...applied to investigate cracking process and mechanism in civil engineering. However, crack classification in AE parameter analysis mostly derives from the empirical relation between the RA value and the average frequency, and the crack classification criterion, i.e., the optimal transition line between shear and tensile cracks in the parameter analysis has not been determined yet. Based on statistical analysis of dominant frequency characteristics of AE signals, a new method is proposed for determining the optimal transition line for crack classification in AE parameter analysis. Spectrum analyses of AE waveform data in the representative specimens are carried out to acquire the dominant frequency of AE waveforms. Proportions of waveforms distributed in low and high dominant frequency bands (L-type and H-type waveforms) are determined. The ratios of tensile and shear cracks, viewed as measurements, are determined by the statistical analysis of dominant frequency characteristics of AE waveforms. For a series of different transition line, the predicted ratios of tensile and shear cracks in AE parameter analysis are determined. The optimal transition line is determined to be the one corresponding to the least square difference between predicted data and measurements. The determined optimal transition line can be directly applied for crack classification in AE parameter analysis in the subsequent experiments of this brittle material. The reliability of the proposed method were validated by laboratory tests of rock subjected to compression. It can be found that the optimal transition line in the parameter analysis is approximately from 1:100 to 1:500 for brittle rock under compression. The findings in this study contributes to the enhancement of the accuracy and efficiency of AE source mechanism and damage process analysis.
With the serious impact of fossil fuels on the environment and the rapid development of the global economy, the development of clean and usable energy storage devices has become one of the most ...important themes of sustainable development in the world today. Supercapacitors are a new type of green energy storage device, with high power density, long cycle life, wide temperature range, and both economic and environmental advantages. In many industries, they have enormous application prospects. Electrode materials are an important factor affecting the performance of supercapacitors. MnO2‐based materials are widely investigated for supercapacitors because of their high theoretical capacitance, good chemical stability, low cost, and environmental friendliness. To achieve high specific capacitance and high rate capability, the current best solution is to use MnO2 and carbon composite materials. Herein, MnO2–carbon composite as supercapacitor electrode materials is reviewed including the synthesis method and research status in recent years. Finally, the challenges and future development directions of an MnO2–carbon based supercapacitor are summarized.
In this paper, the mechanism of MnO2‐based supercapacitors is summarized, and the synthesis method and research status of MnO2‐carbon based supercapacitor electrode materials in recent years are reviewed. Finally, the challenges and future development directions of MnO2‐carbon based supercapacitors are discussed.
Covalent organic frameworks (COFs) with 2D π‐conjugation were designed and synthesized as molecular photosensitizers for efficient photodynamic therapy. Two molecules, ...5′,5′′′′‐(1,4‐phenylene)bis((1,1′:3′,1′′‐terphenyl‐4,4′′‐dicarbaldehyde)) (L‐3C) and 4,4′,4′′‐(1,4‐phenylene)bis((2,2′:6′,2′′‐terpyridine‐5,5′′‐dicarbaldehyde)) (L‐3N), inactive to generating reactive oxygen species (ROS), were linked to form two COFs, COF‐808 and COF‐909, respectively, exhibiting excellent ROS production efficiency. The high permanent porosity of these COFs (surface areas 2270 and 2610 m2 g−1) promoted diffusion of both oxygen and release of ROS in cells. This, combined with the excellent photostability and biocompatibility, led to excellent PDT performance. In vitro, over 80 % of tumor cells were killed after PDT treatment using COF‐909 at the concentration of 50 μg mL−1 for 150 s. In vivo, drastic reduction of tumor size was observed (from 9 mm to less than 1 mm) after 10 day treatment.
Covalent organic frameworks (COFs) with 2D π‐conjugation were designed and synthesized as molecular photosensitizers for efficient photodynamic therapy. Two molecules inactive to generating reactive oxygen species (ROS) were linked to form two COFs exhibiting excellent ROS production efficiency. The high permanent porosity of these COFs promoted both the diffusion of oxygen and the release of ROS in cells.
A magnetic CdS quantum dot (Fe3O4/polydopamine (PDA)/CdS) was synthesized through a facile and convenient method from inexpensive starting materials. Characterization of the prepared catalyst was ...performed by means of FTIR spectroscopy, XRD, SEM, TEM, energy‐dispersive X‐ray spectroscopy, and vibrating‐sample magnetometer techniques. Fe3O4/PDA/CdS was found to be a highly active photocatalyst for the amidation of aromatic aldehydes by using air as a clean oxidant under mild conditions. The photocatalyst can be recovered by magnetic separation and successfully reused for five cycles without considerable loss of its catalytic activity.
Going greener: Magnetic CdS quantum dots are designed for application as an efficient photocatalyst for the oxidative amidation of aldehydes by using air as the oxidant under mild conditions. The photocatalyst can be recovered by magnetic separation and successfully reused in five cycles without considerable loss of catalytic activity.
Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four ...kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non‐drug‐loaded nanoformulations (i.e., metal nanoparticles and molecular self‐assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included. According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task‐specific applications by integrating specific materials, ligands, as well as methods. In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle‐targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects. Finally, the related challenges of critical re‐evaluation of this emerging field are presented.
The rapid development in the field of subcellular targeted cancer therapy is reviewed systemically and comprehensively on account of six sets of treatment modalities: chemotherapy, gene therapy, PDT, hyperthermia, non‐drug‐loaded nanoformulations, and synergistic combined therapy.
While microbial‐based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which ...possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota‐modulating material. Through the host–guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics‐encapsulated probiotic spores (spores‐dex) are prepared. It is found that spores‐dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum, and thereby produces anti‐cancer short‐chain fatty acids (SCFAs). Additionally, spores‐dex regulate the gut microbiota, augment the abundance of SCFA‐producing bacteria (e.g., Eubacterium and Roseburia), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug‐loaded spores‐dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.
Through host–guest chemistry between Clostridium butyricum and chemically modified prebiotic dextran, prebiotics‐encapsulated probiotic spores (spores‐dex) are prepared to achieve oral bacterial treatment of colon cancer.
To engineer patient‐derived cells into therapy‐purposed biologics is a promising solution to realize personalized treatments. Without using gene‐editing technology, a live cell‐typed therapeutic is ...engineered for tumor treatment by artificially reprogramming macrophages with hyaluronic acid‐decorated superparamagnetic iron oxide nanoparticles (HIONs). This nanoparticle‐assisted cell‐reprogramming strategy demonstrates profound advantages, due to the combined contributions from the biological regulation of HIONs and the intrinsic nature of macrophages. Firstly, the reprogrammed macrophages present a substantial improvement in their innate capabilities, such as more effective tumor targeting and more efficient generation of bioactive components (e.g., reactive oxygen species, bioactive cytokines) to suppress tumor growth. Furthermore, this cell therapeutic exhibits cytostatic/proapoptotic effects specific to cancer cells. Secondly, HIONs enable macrophages more resistant to the intratumoral immunosuppressive environment. Thirdly, the macrophages are endowed with a strong ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine‐like manner. Consequently, a synergistic tumor‐inhibition effect is achieved. This study shows that engineering nanomaterial‐reprogrammed live cells as therapeutic biologics may be a more preferable option to the commonly used approaches where nanomaterials are administrated to induce bioresponse of certain cells in vivo.
A live cell‐typed therapeutic is engineered for tumor treatment by reprogramming macrophages with HION nanoparticles. The advantage of this ex vivo cell‐reprogramming strategy is evidenced by cancer‐cell‐specific toxicity, more efficient production of bioactive components, stronger resistance against intratumoral immunosuppression, and favorable ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine‐like manner.
Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully ...satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of "charging" bacteria with a nano-photocatalyst to strengthen their metabolic activities. Carbon nitride (C
N
) is combined with Escherichia coli (E. coli) carrying nitric oxide (NO) generation enzymes for photo-controlled bacterial metabolite therapy (PMT). Under light irradiation, photoelectrons produced by C
N
can be transferred to E. coli to promote the enzymatic reduction of endogenous NO
to cytotoxic NO with a 37-fold increase. In a mouse model, C
N
loaded bacteria are perfectly accumulated throughout the tumor and the PMT treatment results in around 80% inhibition of tumor growth. Thus, synthetic materials-remodeled microorganism may be used to regulate focal microenvironments and increase therapeutic efficiency.