Biology subjects

He, X.-L.

Publications and source records attributed to He, X.-L..

3 recordsLinked to original sources

bioRxiv2026

Compartmentalized Nanozyme Transduction Enables Regenerative Molecular Amplification for Multiplexed miRNA-Based Prostate Cancer Stratification

Circulating microRNAs (miRNAs) have emerged as promising liquid biopsy markers; however, their clinical translation is restricted by low abundance, biological heterogeneity, and the complexity of multiplex profiling. Herein, we develop a targeted cycling-mediated duplex-specific nuclease (DSN)-nanozyme signal amplification platform (TC-DSN-Nano) that establishes a compartmentalized catalytic transduction strategy for multiplexed miRNA analysis. By encapsulating gold nanozymes within liposomal nanoreactors, this platform spatially separates molecular recognition from catalytic signal generation, preserving nanozyme activity during sensor construction. Upon target miRNA recognition, DSN-mediated recycling induces regenerative release of nanozyme-loaded liposomes from magnetic substrates, converting individual miRNA molecules into amplified catalytic outputs without conventional nucleic acid amplification. The platform enables programmable profiling of six prostate cancer (PCa) associated miRNAs in serum samples. Furthermore, machine learning-assisted integration of multiplexed miRNA signatures enables accurate discrimination among healthy donors, nonmetastatic PCa patients, and metastatic PCa patients, achieving an overall classification accuracy of 90.5%. This work establishes a general compartmentalized nanozyme transduction framework that integrates molecular recycling, catalytic amplification, and computational analysis for liquid biopsy-based cancer stratification.

bioengineering↗

bioRxiv2026

Programmable Allosteric DNAzyme Coupled with CRISPR/Cas12a System for Multiplexed and Sensitive Detection of Extracellular Vesicle Derived MicroRNAs

Extracellular vesicle (EV)-derived microRNAs serve as important biomarkers for cancer diagnosis, yet their accurate detection remains limited by insufficient control of nucleic acid recognition and signal activation. Here, we identified a previously unrecognized feature of CRISPR/Cas12a, in which incorporation of ribonucleotides into single stranded DNA targets modulates Cas12a activation efficiency, revealing a hybrid DNA/RNA-dependent regulation of Cas12a activity. Leveraging this mechanism, we established a programmable detection strategy that enables sequence dependent tuning of Cas12a activation without the need for target amplification. By coupling DNAzyme mediated cleavage with Cas12a trans-cleavage, a cascade signal amplification system was established, enabling highly sensitive and selective detection of miRNAs. To facilitate clinical applications, an EV-based sample processing strategy was integrated to simplify isolation of EV associated miRNAs and allow direct miRNA detection without conventional RNA extraction. The resulting platform demonstrated robust discrimination of multiple miRNA targets in clinical cohorts and supported accurate classification of cancer subtypes according to expression signatures. By integrating machine learning analysis, the system accurate distinguished breast cancer (BC) patients from healthy donors (HD), as well as triple-negative breast cancer (TNBC) from BC. This study provides a mechanism-guided strategy for programmable CRISPR-based nucleic acid detection in complex biological samples.

bioengineering↗

bioRxiv2021

Homo-harringtonine (HHT) - A highly effective drug against coronaviruses and the potential for large-scale clinical applications

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins ([~]16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.

microbiology↗