Tumor-derived exosomes are crucial for early non-invasive and accurate tumor diagnosis in clinical. The development of highly sensitive, simple and intuitive exosome assays has sparked a research upsurge in clinical diagnostics. Here, we develop a bio-responsive the intelligent DNA hydrogel loaded with CRISPR/Cas12a for universal and ultrasensitive detection of the exosomes. The aptamer serves as the target response unit and switch of the intelligent DNA hydrogel network. The target competitively disintegrates the region of the DNA linkers then Cas12a/crRNA encapsulated in the intelligent DNA hydrogel can be released and activated by the collateral sequence, resulting in a high fluorescent intensity for exosome detection at the detection limit of 119 particles/μL. Moreover, a prefabricated colorimetric tube is made by loading a colorimetric filter membrane on the tube lid and intelligent DNA hydrogel on the tube bottom, which enables one-pot portable colorimetric detection. Without the need for laboratory instruments and professionals, this strategy allows for naked eye detection with LOD as low as 104 particles/μL, and shows great applicability in distinguishing between healthy individuals, pretreatment patients, and post treatment patients after obtaining a testable analyte. Collectively, this study constructs an ultra-sensitive detection platform for exosomes, which enables one-step sensing and dual signal output, making it a promising tool for the application of liquid biopsy based on exosomes in clinical diagnosis.

Rabies is a lethal infectious disease caused by rabies virus (RABV). The mortality rate is very high after the appearance of clinical symptoms, with a survival rate of almost 0%. There is presently no cure for rabies. In the present study, we investigated whether the extract of Shougong powder-a calcium powder prepared from gecko that has demonstrated immunomodulatory properties in mice-is an effective treatment for rabies. The antiviral effects of the extract were evaluated both in vitro and in vivo with the cytotoxicity and antiviral assays and by immunofluorescence analysis, quantitative real-time (qRT)-PCR, and western blotting. The results showed that Shougong powder and its extract increased survival rate in RABV-infected mice is up to 60% and 50% respectively, even in 20 times of LD50. Whereas the control groups treated with Isoprinosine (IPS) or saline are only 20% and 0% survival (P=0.011). qRT-PCR and western blot analyses showed that the extract strongly inhibited viral mRNA expression and protein synthesis in vitro: expression of the N, P, M, G, and L genes of RABV was decreased by 28.8%–45.0% in the IPS group (P<0.05) and by 50.1%–59.0% in the extract group (P<0.05) relative to the control group. These results demonstrate that Shougong powder has antiviral effects against RABV and can potentially be used for the treatment for rabies.