Abstract:Due to their small size and facile modification, nanomaterials often show special physical, chemical and biological properties. Nanozymes are nanomaterials with enzyme-like activities. Since the “from 0 to 1” discovery of the intrinsic peroxidase-like activity of ferromagnetic nanoparticles[1], functional nanomaterials with intrinsic enzyme-like properties have attracted enormous interests, and nanozymology has become an emerging field bridging nanotechnology and biology. More than 300 nanomaterials with enzymatic activity (nanozymes) were reported from 300 laboratories across 29 countries, and the application of nanozymes has been extended to medicine, agriculture, environment and pharmaceutics[5]. In this special issue, the progression of Metal-Organic Framework nanozymes was summarized, the application of Fe-based nanozyme in the detection of circulating tumor cells was introduced, and tunneling nanotubes, a novel type of signal transmission structure in neuronal cells, was reported. I hope this special issue will be helpful for readers from multidiscipline fields.

Abstract:A kind of nanomaterials with enzyme-mimicking catalytic activity, named as nanozymes, have attracted the attention of researchers. Compared with natural enzymes, nanozymes exhibit the advantages of simple production, low cost and good stability. As a new class of porous coordination polymers, metal-organic frameworks (MOFs) possess many attractive properties, such as structural diversity, pore size tailorability, high specific surface area, and controllable porosity. MOFs-based nanozymes are attracting growing attention because of protection of the ordered framework and the adjustable structure. In this review, we summarize the construction of different types of MOFs-based nanozymes, including pristine MOFs, MOFs with modification, MOF-based composites, and MOF derivatives. Then, the typical applications of MOF-based nanozymes in the detection of various analytes are reviewed. We also summarized and compared the characteristic of MOFs-based nanozymes in different construction types. Finally, the current challenges and future developments of MOFs-based nanozyme are also discussed.

Abstract:Hydrolases are a class of more than 200 individual proteins that catalyze the hydrolysis of a range of unique chemical bonds. However, the inherent disadvantages of natural enzymes, such as variability, high cost, laborious preparation and difficult recovery, greatly limit their practical applications. To overcome these shortcomings, researchers have been devoted to the exploration of hydrolases mimics for a long time. Since the discovery of Fe₃O₄ nanoparticles as peroxidase mimics in 2007, a large number of studies on nanoenzymes have continued to emerge. Compared with natural enzymes, nanoenzymes have the advantages such as simple preparation, large-scale production, strong environmental tolerance, low preparation and storage costs, and reusability. Nanohydrolase are nanomaterials with hydrolase activity,and the hydrolase activity of metal organic frame materials, carbon based nanomaterials and gold nanoparticles has been reported. In recent years, the research field of nano hydrolase has entered a booming period, but so far no one has reviewed nanohydrolase. In this review, we first classifies nanohydrolases according to the different substrates and discusses their catalytic mechanisms, then summarizes the factors affecting the activity of nanohydrolases and the application of nanohydrolases, and finally summarizes and discusses the current challenges and future prospects of nanohydrolases.

Abstract:With the development of nanotechnology, nanomaterials with controllable structure, multifunctional surface and good biocompatibility have been widely used in various aspects of biomedicine. As an important blood biomarker, circulating tumor cells (CTC) are the "seeds" of tumor metastasis. With the flow of blood, tumor cells with strong vitality can pass through blood vessels and gather at the distal end to form tiny tumor thrombi. Therefore, the detection of CTC can be used for early diagnosis of cancer and assessment of metastasis. The application of new nanomaterials and nanomaterial characterization measurement technology has a great impact on the progress of CTC analysis technology. In recent years, the capture and detection of CTC based on nanomaterials and microfluidic technology has become a research hotspot in liquid biopsy, and this technology has been gradually extended to clinical applications. This article reviews the role of nanomaterials and nanotechnology in the capture and detection of CTC, and looks forward to the application prospects of bioanalysis in this field.

Abstract:Tunneling nanotubes (TNTs) are F-actin-based thin channel-like structures connecting distant cells, which provide a new route for intercellular communication. Since TNTs are discovered, an increasing number of studies have demonstrated their roles in the transfer of diverse cargoes between connecting cells, including signaling molecules, RNAs, proteins, organelles, and even pathogens, which illustrate the diversity and complexity of TNTs' function. TNTs have been found in various types of cells, including neuronal cells. In the nervous system, the formation of TNTs between neurons or between neurons and astrocytes mediates electrical coupling and the transfer of pathogenic proteins associated with neurodegenerative diseases. Here, we summarized the current results of TNTs in the nervous system, including its formation, regulatory factors, functions, and potential benefits in the treatment of diseases.

Abstract:L-amino acid oxidases (LAAOs) are an important class of oxidoreductases that participate in the metabolism of amino acids. Employing oxygen molecule as the electron acceptor, LAAOs catalyze the oxidative deamination of L-amino acids and produce corresponding alpha keto acids, ammonia (NH₃) and hydrogen peroxide (H₂O₂). LAAOs with high substrate specificity can recognize the preferred amino acid specially. Therefore, LAAOs with high substrate specificity are promising in the application of chiral amine compounds resolution, alpha keto acid biosynthesis, and especially, in the detection of certain amino acids in clinical and food samples. Therefore, specific LAAOs has attracted wide attention in recent years. In this review, we will focus on the recent progress in LAAOs researches. We will emphasize the substrate specificity, structure-function relationship, and family evolution of these enzymes. We will also discuss the applications of these enzymes in biocatalysis and amino acid detection. This review will provide guidance for molecular mechanism research and industrial applications of LAAOs.

Abstract:To defend against the invasion of phages, most Archaea and bacteria possess the adaptive immune systems, which are formed by clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins. To counteract the CRISPR-Cas systems, phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-dependent response. AcrVA2 from Moraxella bovoculi is an inhibitor of Type V-A CRISPR-Cas system. However, the structure and inhibition mechanism of AcrVA2 remain to be elucidated. Here we report the crystal structures of AcrVA2 in the apo state and MbCas12a^620-636-AcrVA2 complex. AcrVA2 adopts a novel α-β fold and binds to MbCas12a in free state. The structure of MbCas12a^620-636-AcrVA2 complex reveals that AcrVA2 interacts with MbCas12a via hydrogen bonds and salt bridges, as well as hydrophobic interaction. These results suggest that AcrVA2 affect the activity of Cas12a by binding to the MbCas12a in the apo state. These results provide significant insights into the mechanism of AcrVA2 disabling Type V-A CRISPR-Cas system.

Abstract:Lactobacillus acidophilus is a kind of probiotics. The previous research found that β-glucosidase (BGL) produced by Lactobacillus acidophilus GIM1.208 has high activity. In order to elucidate its structure and characteristics, the target gene of Lactobacillus acidophilus GIM1.208 BGL was obtained with PCR and successfully expressed in E. coli. Protein samples with a purity of more than 90% was obtained by nickel affinity chromatography. Then the secondary structure of BGL was detected by circular dichroism spectroscopy (CD) and its tertiary structure was analyzed by homology modeling method. The enzymatic properties of Lactobacillus acidophilus BGL was also studied. The results show that the molecular mass of Lactobacillus acidophilus BGL is 52 ku, the concentration after purification is 1.88 g/L. The secondary structure of Lactobacillus acidophilus BGL includes 15.9% α-helix, 44.1% β-sheet, 18.1% β-turn, and 27.2% random coil. Homology modeling analyzation showed that 8 β-sheets and 8 α-helices were included in 3D structure of Lactobacillus acidophilus BGL, and the whole protein is conical in shape. Lactobacillus acidophilus BGL has good glucose tolerance and NaCl tolerance. The optimal temperature and the optimal pH of this enzyme is 47℃ and 5.6, respectively. Lactobacillus acidophilus BGL has high stability in the range of 20℃-50℃ and pH 2.2-6.0. The inhibitory effect of ethyl acetate and methanol on enzyme activity is obvious, and Fe³⁺ and Fe²⁺ have significant activation effect on enzyme. These results provide important reference basis for the subsequent functional exploration and application research of Lactobacillus acidophilus BGL.

Abstract:Exosomes play an important role in the fulfillment of cellular physiological activities and are strongly involved in the pathological processes of numerous diseases. Investigating the behaviors of exosomes is therefore of critical significance for revealing the underlying mechanisms guiding life mysteries and diseases. Nevertheless, due to the lack of adequate tools, the detailed structures and mechanics of living exosomes in their native states are still not fully understood. In this work, atomic force microscopy (AFM), a powerful multifunctional tool for characterizing native biological samples without pretreatments under aqueous conditions, was utilized to probe the nanostructures and mechanics of single living exosomes prepared from clinical cancer patients. Firstly, by attaching exosomes isolated from the bone marrow of lymphoma patients onto the substrates with electrostatic adsorption, single living exosomes were clearly visualized by AFM in situ imaging in liquids. The morphological differences of exosomes in liquids and in air were revealed. Secondly, the mechanical properties of single living exosomes were quantitatively and visually studied by AFM indentation assays and AFM multiparametric imaging, respectively. Finally, structural and mechanical changes of exosomes after the treatment of chemical fixation were revealed by AFM. The research benefits investigating the structures and properties of living exosomes at the nanoscale for comprehensively understanding the behaviors of exosomes, which will have potential impacts on the studies of exosomes.