Enzyme Reaction-Assisted Programmable Transcriptional Switches for Bioactive Molecule Detection.

Bioactive molecules are highly worthwhile to recognize and explore the latent pathogenic mechanism. Conventional methods for bioactive molecule detection, including mass spectrometry and fluorescent probe imaging, are limited due to the complex processing and signal interference. Here, we designed enzyme-reaction-assisted programmable transcriptional switches for the detection of bioactive molecules. The approach is based on the use of programmable enzyme site-specific cleavage-assisted DNA triplex-based conformational switches that, upon responding to bioactive molecules, can trigger the transcription of fluorescent light-up aptamers. Thanks to the programmable nature of the sensing platform, the method can be adapted to different bioactive molecules, and we demonstrated the enzyme-small molecule catalytic reaction combination of myeloperoxidase (MPO)-hydrogen peroxide (H2O2) as a model that transcriptional switches was capable of detecting H2O2 and possessed the specificity and anti-interference ability in vitro. Furthermore, we successfully applied the switches into cells to observe the detection feasibility in vivo, and dynamically monitored changes of H2O2 in cellular oxidative stress levels. Therefore, we attempt to amalgamate the advantages of enzyme reaction with the pluripotency of programmable transcriptional switches, which can take both fields a step further, which may promote the research of biostimuli and the construction of DNA molecular devices.

Liquid-colloid-solid modular assembly for three-dimensional electrochemical biosensing of small molecules.

Electrochemical biosensors hold promise for advanced analytical applications in modern life analysis due to their miniaturization and cost-effectiveness. Nevertheless, their implementation in complex biological systems necessitates overcoming challenges related to timeliness, sensitivity, and interference resistance. Here, we developed a novel DNA hydrogel three-dimensional electron transporter through liquid-colloid-solid assembly, integrating electronic mediators and employing porous electrode covers with 3D printing technology. Our approach facilitated the fabrication of a high-performance electrochemical sensor for small molecule detection, leveraging target-specific aptamers and catalytic hairpin assembly (CHA) elements within the DNA hydrogel, which exhibited outstanding selectivity, sensitivity, and universality, achieving detection limits of 0.047 nM for kanamycin and 2.67 pM for ATP. Furthermore, this sensor could detect kanamycin in real samples, demonstrating good accuracy and robust anti-interference capabilities in human serum. Our work not only possesses substantial application value in clinical sample analysis but also represents a breakthrough in traditional strategies, thereby contributing to advancements in the application of electrochemical biosensors for life analysis.

Microfluidics for diagnosis and treatment of cardiovascular disease.

Cardiovascular disease (CVD), a type of circulatory system disease related to the lesions of the cardiovascular system, has become one of the main diseases that endanger human health. Currently, the clinical diagnosis of most CVDs relies on a combination of imaging technology and blood biochemical test. However, the existing technologies for diagnosis of CVDs still have limitations in terms of specificity, detection range, and cost. In order to break through the current bottleneck, microfluidic with the advantages of low cost, simple instruments and easy integration, has been developed to play an important role in the early prevention, diagnosis and treatment of CVDs. Here, we have reviewed the recent various applications of microfluidic in the clinical diagnosis and treatment of CVDs, including microfluidic devices for detecting CVD markers, the cardiovascular models based on microfluidic, and the microfluidic used for CVDs drug screening and delivery. In addition, we have briefly looked forward to the prospects and challenges of microfluidics in diagnosis and treatment of CVDs.

Sperm-like nanocarriers for ultrafast delivery of antisense DNA.

Although various nanomaterials have been designed as intracellular delivery tools, the following aspects have become obstacles to limit their development, like a complex and time-consuming synthesis process, as well as relatively limited application areas (i.e. biosensing or cell imaging). Here, we developed a novel nano-delivery system called "nano-sperm" with low cytotoxicity and high biocompatibility. In this system, we used DNA oligonucleotides as a backbone to synthesize a nanostructure with silver nanoclusters in the head and functional fragments in the tail, which is shaped like a sperm, to achieve dual functions of ultrafast delivery and imaging/therapy. As a model, we analyzed the possibility of the "nano-sperm" carrying DNA with different structures for imaging or survivin-asDNA for tumor therapy. Therefore, this work reports a novel bifunctional high-speed delivery vehicle, which successfully fills the gap in the field of tumor therapy using DNA-templated nanoclusters as a delivery vehicle.