DNA-based programmable gate arrays for general-purpose DNA computing.

The past decades have witnessed the evolution of electronic and photonic integrated circuits, from application specific to programmable1,2. Although liquid-phase DNA circuitry holds the potential for massive parallelism in the encoding and execution of algorithms3,4, the development of general-purpose DNA integrated circuits (DICs) has yet to be explored. Here we demonstrate a DIC system by integration of multilayer DNA-based programmable gate arrays (DPGAs). We find that the use of generic single-stranded oligonucleotides as a uniform transmission signal can reliably integrate large-scale DICs with minimal leakage and high fidelity for general-purpose computing. Reconfiguration of a single DPGA with 24 addressable dual-rail gates can be programmed with wiring instructions to implement over 100 billion distinct circuits. Furthermore, to control the intrinsically random collision of molecules, we designed DNA origami registers to provide the directionality for asynchronous execution of cascaded DPGAs. We exemplify this by a quadratic equation-solving DIC assembled with three layers of cascade DPGAs comprising 30 logic gates with around 500 DNA strands. We further show that integration of a DPGA with an analog-to-digital converter can classify disease-related microRNAs. The ability to integrate large-scale DPGA networks without apparent signal attenuation marks a key step towards general-purpose DNA computing.

Twisted DNA Origami-Based Chiral Monolayers for Spin Filtering.

DNA monolayers with inherent chirality play a pivotal role across various domains including biosensors, DNA chips, and bioelectronics. Nonetheless, conventional DNA chiral monolayers, typically constructed from single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA), often lack structural orderliness and design flexibility at the interface. Structural DNA nanotechnology has emerged as a promising solution to tackle these challenges. In this study, we present a strategy for crafting highly adaptable twisted DNA origami-based chiral monolayers. These structures exhibit distinct interfacial assembly characteristics and effectively mitigate the structural disorder of dsDNA monolayers, which is constrained by a limited persistence length of ∼50 nm of dsDNA. We highlight the spin-filtering capabilities of seven representative DNA origami-based chiral monolayers, demonstrating a maximal one-order-of-magnitude increase in spin-filtering efficiency per unit area compared with conventional dsDNA chiral monolayers. Intriguingly, our findings reveal that the higher-order tertiary chiral structure of twisted DNA origami further enhances the spin-filtering efficiency. This work paves the way for the rational design of DNA chiral monolayers.

Programming and monitoring surface-confined DNA computing.

DNA-based molecular computing has evolved to encompass a diverse range of functions, demonstrating substantial promise for both highly parallel computing and various biomedical applications. Recent advances in DNA computing systems based on surface reactions have demonstrated improved levels of specificity and computational speed compared to their solution-based counterparts that depend on three-dimensional molecular collisions. Herein, computational biomolecular interactions confined by various surfaces such as DNA origamis, nanoparticles, lipid membranes and chips are systematically reviewed, along with their manipulation methodologies. Monitoring techniques and applications for these surface-based computing systems are also described. The advantages and challenges of surface-confined DNA computing are discussed.

TMED3 promotes cell proliferation and motility in breast cancer and is negatively modulated by miR-188-3p.

BACKGROUND: The role of TMED3 involved in cancers has been seldom described, let alone in breast cancer. To explore the clinicopathological significance of TMED3 expression and the biological roles involved in breast cancer cells, we undertook the study. METHODS: Immunohistochemistry was performed to observe the pattern of TMED3 expression in breast cancer tissues, totaling 224 cases; followed by detailed statistical analysis between TMED3 expression versus clinicopathological information available. To explore the role of TMED3 involved in the malignant behaviors of breast cancer cells, wound-healing and Transwell assays were conducted to evaluate the variation of migration and invasion of MCF-7 and MDA-MB-231 cells whose TMED3 has been stably silenced using lenti-viral based short hairpin RNA (shRNA) vectors. MTT, clonogenic assay and xenograft nude mice model were undertaken to observe the variation of proliferation both in vitro and in vivo. RESULTS: It was shown that elevated TMED3 markedly correlated with ER, PR, Her-2 status, and lymph nodes metastases in addition to significant association with poor overall prognosis. In vitro, TMED3 was shown to promote proliferation, migration and invasion of breast cancer cells. Moreover, miR-188-3p was identified as a novel negative regulator of TMED3 in breast cancer, which can slow down the proliferation, migration and invasion of MCF-7 cells. Results from in vivo xenograft nude mice models showed that lenti-viral based miR-188-3p re-expression can markedly impair the tumor growth. CONCLUSIONS: Our data define and bolster the oncogenic role of TMED3 in breast cancer.