Research on a Framework for Chinese Argot Recognition and Interpretation by Integrating Improved MECT Models.

In underground industries, practitioners frequently employ argots to communicate discreetly and evade surveillance by investigative agencies. Proposing an innovative approach using word vectors and large language models, we aim to decipher and understand the myriad of argots in these industries, providing crucial technical support for law enforcement to detect and combat illicit activities. Specifically, positional differences in semantic space distinguish argots, and pre-trained language models' corpora are crucial for interpreting them. Expanding on these concepts, the article assesses the semantic coherence of word vectors in the semantic space based on the concept of information entropy. Simultaneously, we devised a labeled argot dataset, MNGG, and developed an argot recognition framework named CSRMECT, along with an argot interpretation framework called LLMResolve. These frameworks leverage the MECT model, the large language model, prompt engineering, and the DBSCAN clustering algorithm. Experimental results demonstrate that the CSRMECT framework outperforms the current optimal model by 10% in terms of the F1 value for argot recognition on the MNGG dataset, while the LLMResolve framework achieves a 4% higher accuracy in interpretation compared to the current optimal model.The related experiments undertaken also indicate a potential correlation between vector information entropy and model performance.

Allosteric aptasensor-initiated target cycling and transcription amplification of light-up RNA aptamer for sensitive detection of protein.

The early detection of biomarker proteins in clinical samples is of great significance for the diagnosis of diseases. However, it is still a challenge to detect low-concentration protein. Herein, a label-free aptamer-based amplification assay, termed the ATC-TA system, that allows fluorescence detection of very low numbers of protein without time-consuming washing steps and pre-treatment was developed. The target induces a conformational change in the allosteric aptasensor, triggers the target cycling and transcription amplification, and ultimately converts the input of the target protein into the output of the light-up aptamer (R-Pepper). It exhibits ultrahigh sensitivity with a detection limit of 5.62 fM at 37 â„ƒ and the accuracy is comparable to conventional ELISA. ATC-TA has potential application for the detection of endogenous PDGF-BB in serum samples to distinguish tumor mice from healthy mice at an early stage. It also successfully detects exogenous SARS-CoV-2 spike proteins in human serum. Therefore, this high-sensitive, universality, easy-to-operate and cost-effective biosensing platform holds great clinical application potential in early clinical diagnosis.

Antitumor Effect of Anti-c-Myc Aptamer-Based PROTAC for Degradation of the c-Myc Protein.

Targeting "undruggable" targets with intrinsically disordered structures is of great significance for the treatment of disease. The transcription factor c-Myc controls global gene expression and is an attractive therapeutic target for multiple types of cancers. However, due to the lack of defined ligand binding pockets, targeted c-Myc have thus far been unsuccessful. Herein, to address the dilemma of lacking ligands, an efficient and high throughput aptamer screening strategy is established, named polystyrene microwell plate-based systematic evolution of ligands by exponential enrichment (microwell-SELEX), and identify the specific aptamer (MA9C1) against c-Myc. The multifunctional aptamer-based Proteolysis Targeting Chimeras (PROTAC) for proteolysis of the c-Myc (ProMyc) is developed using the aptamer MA9C1 as the ligand. ProMyc not only significantly degrades c-Myc by the ubiquitin-proteasome system, but also reduces the Max protein, synergistically inhibiting c-Myc transcriptional activity. Combination of the artificial cyclization and anti-PD-L1 aptamer (PA1)-based delivery system, circular PA1-ProMyc chimeras achieve tumor regression in the xenograft tumor model, laying a solid foundation for the development of efficacious c-Myc degrader for the clinic. Therefore, this aptamer-based degrader provides an invaluable potential degrader in drug discovery and anti-tumor therapy, offering a promising degrader to overcome the challenge of targeting intractable targets.

Anti-tumor effect of PD-L1-targeting antagonistic aptamer-ASO delivery system with dual inhibitory function in immunotherapy.

Checkpoint inhibitor antibody therapy by blocking the interaction of surface programmed death-ligand 1(PD-L1) and programmed cell death protein 1(PD-1) has promising advantages in cancer immunotherapy. However, the response of many patients remains unsatisfactorily, suspected to be relevant to PD-L1 located in other cellular compartments and antibodies do not have access to the intracellular compartments. Herein, we identify a PD-L1-targeting DNA aptamer (PA9-1) with dual roles, including an antagonist and a delivery agent dependent on PD-L1 internalization. And we design the PD-L1-targeting antagonistic aptamer-ASO delivery system (PA9-1-ASO), with synergistic inhibitory PD-L1 activity involving the combination of blockade and silencing mechanisms. This chimera not only blocks PD-L1/PD-1 but also achieves targeted delivery of the conjugated ASO to reduce both surface PD-L1 and total PD-L1 expression. Compared with the single blockade, this chimera with the dual inhibitory function synergistically inhibits PD-L1 to amplify immunotherapeutic efficacy, providing a promising synergistic strategy for immunotherapy.

A genetically encoded fluorescent biosensor for monitoring ATP in living cells with heterobifunctional aptamers.

Visualizing the dynamics of ATP in living cells is key to understanding cellular energy metabolism and related diseases. However, the live-cell applications of current methods are still limited due to challenges in biological compatibility and sensitivity to pH. Herein, a novel label-free fluorescent " turn-on " biosensor for monitoring ATP in living bacterias and mammalian cells was developed. This biosensor (Broc-ATP) employed heterobifunctional aptamers to detect ATP with high sensitivity in vitro. In our system, a very useful tandem method was established by combining four Broc-ATPs with 3 × F30 three-way junction scaffold to construct an intracellular biosensor that achieves sufficient fluorescence to respond to intracellular ATP. This intracellular biosensor can be used for sensitive and specific dynamic imaging of ATP in mammalian cells. Hence, this genetically encoded biosensor provides a robust and efficient tool for the detection of intracellular ATP dynamics and 3 × F30 tandem method expands the application of heterobifunctional aptamers in mammalian cells.

A hairpin-mediated nicking enzymatic signal amplification for nucleic acids detection.

A novel signal amplification to detect nucleic acid, called hairpin-mediated nicking enzymatic signal amplification (HNESA), is developed. This method overcomes the limitation of conventional nicking enzymatic signal amplification (NESA) that the target must contain the nicking endonuclease recognition site by using a hairpin probe containing the nicking endonuclease recognition site as an intermediary. Nucleic acid with any sequence can be amplified by HNESA which substantially improves the substrate-scope of traditional NESA. HNESA could detect nucleic acids (ssDNA and RNA) with a detection limit of 8.3 pM at 55 °C. As low as 68 fM could also be detected by integrating HNESA and strand-displacement amplification (SDA). More importantly, HNESA is quite efficient in distinguish single base mismatched sequences. HNESA has potential application for nucleic acid detection in complex biological samples. Therefore, HNESA with high sensitivity and ultrahigh selectivity, should be a promising tool for nucleic acid research, especially for single nucleotide polymorphism (SNP) detection.