Jiangxi Normal University

MicroRNA (miRNA) plays a crucial role in a great number of human cancers so that the detection of miRNA has been widely acknowledged as an effective strategy for the early discovery and diagnosis of cancer. Building upon conventional strand displacement amplification, the study was introduced a dual strand displacement process to enhance primer amplification efficiency. Additionally, we designed a lateral displacement assembly-based DNA nanostructure, expanding on traditional hairpin structures, and constructed a side-shifted hybrid chain reaction (SHCR) strategy for dual amplification of primer sequences. This approach yielded a three-way junction (3WJ) DNA nanostructure, providing optimal molecular recognition sites. The SHCR facilitated the assembly of fluorescent probes through a straightforward hybridization chain reaction. The target-triggered double strand displacement amplification (DSDA) exhibited high specificity for miRNA-let-7a with the rang from 50 fM to 50 nM, and the biosensor's limit of detection is 22 fM. Moreover, the sensor system performed exceptionally well in detecting real samples, such as cell lysates. Therefore, this work offers a novel strategy for early cancer screening.

Subarachnoid hemorrhage (SAH) represents a severe subtype of stroke, distinguished by its substantial mortality and morbidity rates. It initiates a series of harmful physiological responses, such as increased intracranial pressure, cerebral edema, and neuroinflammation. Pyroptosis, a form of cell death dependent on caspase-1, plays a crucial role in the inflammatory processes following SAH. Recent research indicated that the inhibition of the NLRP3 inflammasome is regarded as a promising therapeutic strategy for mitigating inflammatory responses. Bindarit, a β-blocker with anti-inflammatory properties, has demonstrated potential in mitigating NLRP3-mediated pyroptosis. Nevertheless, its clinical application is limited by its short half-life and inadequate penetration of the blood-brain barrier (BBB). To address these limitations, a novel pH-responsive erythrocyte membrane-biomimetic guanidino-based covalent organic framework (COF) nanocarrier, designated as B@COF_DT-R, has been developed to encapsulate bindarit. This nanocarrier is specifically engineered to enhance drug delivery across the BBB and target the NLRP3/Caspase-1/GSDMD axis, thereby inhibiting neuronal pyroptosis in vitro and vivo. The development of B@COF_DT-R constitutes a substantial advancement in the treatment of SAH. Through the enhancement of drug delivery mechanisms and the targeted modulation of critical inflammatory pathways, this nanocarrier holds the potential to significantly improve therapeutic outcomes for patients suffering from SAH.

Developing covalent organic frameworks (COFs) with excellent detection performance remains challenging. Here, (3-aminopropyl) triethoxysilane (APTES)-functionalized COF-1 was synthesized to obtain COF-1 nanosheets, and the molecule with aggregation induced emission (AIE) characteristic such as 4,4',4″,4″'-(Ethene-1,1,2,2-tetrayl)tetrabenzoic acid(H₄tcpe) or 4',4″',4″"',4″""'-(Ethene-1,1,2,2-tetrakis)tetrakis([1,1'-biphenyl]-4-carboxylic acid)(H₄tcbpe) was adsorbed onto the surface of COF-1 via π-π interaction to construct a fluorescent probe. Owing to the distinctive long-chain, dicarboxyl, and multi-point coordination structure of GSH, the addition of GSH into the COF-1&H₄tcpe/H₄tcbpe probe solution enables its flexible framework to modulate the electron cloud density of the probe leading to block the ICT effect and suppress the rotation of H₄tcpe/H₄tcbpe molecules, leading to fluorescence enhancement. Thus, COF-1&H₄tcpe and COF-1&H₄tcbpe can be used as a probe for the detection of GSH. Compared with COF-1&H₄tcpbe, the COF-1&H₄tcpe probe showed more excellent detection performance, which presented a wider linear range of 0.3-400 μM for GSH, and the detection limit (LOD) for GSH was as low as 0.10 μM. This work provides a new strategy for designing highly fluorescent COF composites with affinity and structural selectivity.