Precise control over the nucleation, growth, and termination of self-assembly processes is a fundamental tool for controlling product yield and assembly dynamics. Mechanisms for altering these processes programmatically could allow the use of simple components to self-assemble complex final products or to design processes allowing for dynamic assembly or reconfiguration. Here we use DNA tile self-assembly to develop general design principles for building complexes that can bind to a growing biomolecular assembly and terminate its growth by systematically characterizing how different DNA origami nanostructures interact with the growing ends of DNA tile nanotubes. We find that nanostructures that present binding interfaces for all of the binding sites on a growing facet can bind selectively to growing ends and stop growth when these interfaces are presented on either a rigid or floppy scaffold. In contrast, nucleation of nanotubes requires the presentation of binding sites in an arrangement that matches the shape of the structure's facet. As a result, it is possible to build nanostructures that can terminate the growth of existing nanotubes but cannot nucleate a new structure. The resulting design principles for constructing structures that direct nucleation and termination of the growth of one-dimensional nanostructures can also serve as a starting point for programmatically directing two- and three-dimensional crystallization processes using nanostructure design.
Background: Lymph node metastasis (LNM) occurs frequently in young papillary thyroid carcinoma (PTC) patients, though the mortality rates are low. We aimed to analyze the relationship between age at diagnosis and LNM in PTC at a population level to elucidate the clinical behavior of PTC. Methods: Data of adult patients with surgically treated PTC and follicular thyroid carcinoma (FTC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) to investigate the relationship between age and clinical characteristics by curve estimation. The adjusted odds ratio of age and LNM rate were determined.Results: A total of 50,347 PTC (48,166) and FTC (2181) (median age: 45 and 50 years, respectively) patients met the inclusion criteria; 44.5% of those with PTC (21,428) had LNM. Rank-sum test analysis indicated differences in distribution of age in LNM-positive and LNM-negative PTC. The relationship between age, tumor size and LNM showed a quadratic curve in PTC. The mean tumor diameter and LNM rate correlated linearly with age in 18-59year-old patients. LNM rate decreased with age (R 2 = 0.932, P < .0001), especially women (R 2 = 0.951, P < .0001).
Conclusion:In young and middle-aged PTC patients, LNM may resolve spontaneously with delayed diagnosis and management. Active surveillance of low-risk PTC is justified.
Alpha-fetoprotein (AFP) is overexpressed in hepatocellular carcinoma (HCC) and could serve as a tumor-associated antigen (TAA) and potential target for adoptive immunotherapy. However, low frequency and severe functional impairment of AFP-specific T cells in vivo hamper adoptive infusion. TAA-specific T cell receptor (TCR) gene transfer could be an efficient and reliable alternation to generate AFP-specific cytotoxic T lymphocytes (CTLs). Autologous dendritic cells (DC) pulsed with AFP158-166 peptides were used to stimulate AFP-specific CTLs. TCR α/β chain genes of AFP-specific CTLs were cloned and linked by 2A peptide to form full-length TCR coding sequence synthesized into a lentiviral vector. Nonspecific activated T cells were engineered by lentivirus infection. Transgenetic CTLs were evaluated for transfection efficiency, expression of AFP158-166-specific TCR, interferon (IFN)-γ secretion, and specific cytotoxicity toward AFP+ HCC cells in vitro and in vivo. Flow cytometry revealed the AFP158-166-MHC-Pentamer positive transgenetic CTLs was 9.86 %. The number of IFN-γ secretion T cells and the specific cytotoxicity toward HpeG2 in vitro and in tumor-bearing NOD/SCID mice were significantly raised in transgenetic CTLs than that of AFP158-166-specific CTLs obtained by peptide-pulsed DCs or control group. TCR gene transfer is a promising strategy to generate AFP158-166-specific CTLs for the treatment of HCC.
We demonstrate a label free and high-throughput microbubble-based acoustic microstreaming technique to isolate rare circulating cells from cancer patients with a capture efficiency of 94% while preserving cell functional integrity within 8 minutes.
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