Brain diseases, including tumors and neurodegenerative disorders, are among the most serious health problems. Non-invasively high-resolution imaging methods are required to gain anatomical structures and information of the brain. In addition, efficient diagnosis technology is also needed to treat brain disease. Rare-earth based materials possess unique optical properties, superior magnetism, and high X-ray absorption abilities, enabling high-resolution imaging of the brain through magnetic resonance imaging, computed tomography imaging, and fluorescence imaging technologies. In addition, rare-earth based materials can be used to detect, treat, and regulate of brain diseases through fine modulation of their structures and functions. Importantly, rare-earth based materials coupled with biomolecules such as antibodies, peptides, and drugs can overcome the blood-brain barrier and be used for targeted treatment. Herein, this review highlights the rational design and application of rare-earth based materials in brain imaging, therapy, monitoring, and neuromodulation. Furthermore, the development prospect of rare-earth based materials is briefly introduced.
Numerous strategies involving multiple cross-linking networks have been applied for fabricating robust hydrogels. Inspired by this, the development of mechanically strong and tough biological fibers by the incorporation of intermolecular linking networks is becoming important. Herein, we present a versatile strategy for the fabrication of protein-saccharide composite fibers through protein-initiated double interacting networks. Three types of lysine-rich bioengineered proteins were introduced and the present multiple cross-linking interactions including electrostatic forces and covalent bonds significantly enhanced the mechanical properties of as-obtained composite fibers. In stark contrast to pristine saccharide or other polymer fibers, the as-obtained composite fibers exhibited outstanding mechanical performance, showing a breaking strength of ∼768 MPa, Young’s modulus of ∼24 GPa, and toughness of ∼69 MJ·m−3, respectively. Thus, this established approach has great potentials to fabricate new generation renewable biological fibers with high performance.
16 May 2024 in Frontiers in Cellular and Infection Microbiology
Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1β (IL-1β) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.
Construction of synthetic circuits that can reprogram genetic networks and signal pathways is a long-term goal for manipulation of biosystems. However, it is still highly challenging to build artificial genetic communications among endogenous RNA species due to their sequence independence and structural diversities. Here we report an RNA-based synthetic circuit that can establish regulatory linkages between expression of endogenous genes in both Escherichiacoli and mammalian cells. This design employs a displacement–assembly approach to modulate the activity of guide RNA for function control of CRISPR/Cas9. Our experiments demonstrate the great effectiveness of this RNA circuit for building artificial connections between expression of originally unrelated genes. Both exogenous and naturally occurring RNAs, including small/microRNAs and long mRNAs, are capable of controlling expression of another endogenous gene through this approach. Moreover, an artificial signal pathway inside mammalian cells is also successfully established to control cell apoptosis through our designed synthetic circuit. This study provides a general strategy for constructing synthetic RNA circuits, which can introduce artificial connections into the genetic networks of mammalian cells and alter the cellular phenotypes.
9 January 2013 in Journal of the American Chemical Society
DNA methylation and demethylation play a key role in the epigenetic regulation of gene expression; however, a series of oxidation reactions of 5-methyl cytosine (5mC) mediated by ten-eleven translocation (TET) enzymes driving demethylation process are yet to be uncovered. To elucidate the relationship between the oxidative processes and structural factors of DNA, we analysed the behavior of TET-mediated 5mC-oxidation by incorporating structural stress onto a substrate double-stranded DNA (dsDNA) using a DNA origami nanochip. The reactions and behaviors of TET enzymes were systematically monitored by biochemical analysis and single-molecule observation using atomic force microscopy (AFM). A reformative frame-like DNA origami was established to allow the incorporation of dsDNAs as 5mC-containing substrates in parallel orientations. We tested the potential effect of dsDNAs present in the tense and relaxed states within a DNA nanochip on TET oxidation. Based on enzyme binding and the detection of oxidation reactions within the DNA nanochip, it was revealed that TET preferred a relaxed substrate regardless of the modification types of 5-oxidated-methyl cytosine. Strikingly, when a multi-5mCG sites model was deployed to further characterize substrate preferences of TET, TET preferred the fully methylated site over the hemi-methylated site. This analytical modality also permits the direct observations of dynamic movements of TET such as sliding and interstrand transfer by high-speed AFM. In addition, the thymine DNA glycosylase-mediated base excision repair process was characterized in the DNA nanochip. Thus, we have convincingly established the system's ability to physically regulate enzymatic reactions, which could prove useful for the observation and characterization of coordinated DNA demethylation processes at the nanoscale.