One prevention and therapeutic strategy for diseases associated with peptide or protein fibrillation is to inhibit or delay the fibrillation process. Carbon dots (C–Dots) have recently emerged as benign nanoparticles to replace toxic quantum dots and have attracted great attention because of their unique optical properties and potential applications in biological systems. However, the effect of C-Dots on peptide or protein fibrillation has not been explored. In this in vitro study, human insulin was selected as a model to investigate the effect of C-Dots on insulin fibrillation. Water-soluble fluorescent C-Dots with sizes less than 6 nm were prepared from carbon powder and characterized by UV–vis spectroscopy, fluorescence, Fourier transform infrared spectrophotometry, X-ray photoelectron spectrometry, transmission electron microscopy, and atomic force microscopy. These C-Dots were able to efficiently inhibit insulin fibrillation in a concentration-dependent manner. The inhibiting effect of C-Dots was even observed at 0.2 μg/mL. Importantly, 40 μg/mL of C-Dots prevent 0.2 mg/mL of human insulin from fibrillation for 5 days under 65 °C, whereas insulin denatures in 3 h under the same conditions without C-Dots. The inhibiting effect is likely due to the interaction between C-Dots and insulin species before elongation. Cytotoxicity study shows that these C-Dots have very low cytotoxicity. Therefore, these C-Dots have the potential to inhibit insulin fibrillation in biological systems and in the pharmaceutical industry for the processing and formulation of insulin.
T-cell receptor–engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of the B-cell lineages, most solid tumors fail to respond significantly to chimeric antigen receptor T cells. T-cell receptor–engineered T-cell therapy, on the other hand, has shown unprecedented promise in treating solid tumors and has attracted growing interest. In order to create an unbiased, comprehensive, and scientific report for this fast-moving field, we carefully analyzed all 84 clinical trials using T-cell receptor–engineered T-cell therapy and downloaded from ClinicalTrials.gov updated by June 11, 2018. Informative features and trends were observed in these clinical trials. The number of trials initiated each year is increasing as expected, but an interesting pattern is observed. NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials. Novel antigens and underrepresented cancers remain to be targeted in future studies and clinical trials. Unlike chimeric antigen receptor T-cell therapy, only about 16% of the 84 clinical trials target against hematological malignancies, consistent with T-cell receptor–engineered T-cell therapy’s high potential for solid tumors. Six pharma/biotech companies with novel T-cell receptor–engineered T-cell ideas and products were examined in this review. Multiple approaches have been utilized in these companies to increase the T-cell receptor’s affinity and efficiency and to minimize cross-reactivity. The major challenges in the development of the T-cell receptor–engineered T-cell therapy due to tumor microenvironment were also discussed here.
Biosensing methods and devices using graphene oxide (GO) have recently been explored for detection and quantification of specific biomolecules from body fluid samples, such as saliva, milk, urine, and serum. For a practical diagnostics application, any sensing system must show an absence of nonselective detection of abundant proteins in the fluid matrix. Because lysozyme is an abundant protein in these body fluids (e.g., around 21.4 and 7 μg/mL of lysozyme is found in human milk and saliva from healthy individuals, and more than 15 or even 100 μg/mL in patients suffering from leukemia, renal disease, and sarcoidosis), it may interfere with detections and quantification if it has strong interaction with GO. Therefore, one fundamental question that needs to be addressed before any development of GO based diagnostics method is how GO interacts with lysozyme. In this study, GO has demonstrated a strong interaction with lysozyme. This interaction is so strong that we are able to subsequently eliminate and separate lysozyme from aqueous solution onto the surface of GO. Furthermore, the strong electrostatic interaction also renders the selective adsorption of lysozyme on GO from a mixture of binary and ternary proteins. This selectivity is confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fluorescence spectroscopy, and UV–vis absorption spectroscopy.
Lytechinus variegatus is a camarodont sea urchin found widely throughout the western Atlantic Ocean in a variety of shallow-water marine habitats. Its distribution, abundance, and amenability to developmental perturbation make it a popular model for ecologists and developmental biologists. Here, we present a chromosomal-level genome assembly of L. variegatus generated from a combination of PacBio long reads, 10X Genomics sequencing, and HiC chromatin interaction sequencing. We show L. variegatus has 19 chromosomes with an assembly size of 870.4 Mb. The contiguity and completeness of this assembly is reflected by a scaffold length N50 of 45.5Mb and BUSCO completeness score of 95.5%. Ab-initio and transcript-informed gene modelling and annotation identified 27,232 genes with an average gene length of 12.6 Kb, comprising an estimated 39.5% of the genome. Repetitive regions, on the other hand, make up approximately 45.4% of the genome. Physical mapping of well-studied developmental genes onto each chromosome reveals non-random spatial distribution of distinct genes and gene families, which provides insight into how certain gene families may have evolved and are transcriptionally regulated in this species. Lastly, aligning RNA-seq and ATAC-seq data onto this assembly demonstrates the value of highly contiguous, complete genome assemblies for functional genomics analyses that is unattainable with fragmented, incomplete assemblies. This genome will be of great value to the scientific community as a resource for genome evolution, developmental, and ecological studies of this species and the Echinodermata.
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