Yuxuan Zhu

Isothermal autocatalytic DNA circuits have been proven to be versatile and powerful biocomputing platforms by virtue of their self-sustainable and self-accelerating reaction profiles, yet they are currently constrained by their complicated designs, severe signal leakages, and unclear reaction mechanisms. Herein, we developed a simpler-yet-efficient autocatalytic assembly circuit (AAC) for highly robust bioimaging in live cells and mice. The scalable and sustainable AAC system was composed of a mere catalytic DNA assembly reaction with minimal strand complexity and, upon specific stimulation, could reproduce numerous new triggers to expedite the whole reaction. Through in-depth theoretical simulations and systematic experimental demonstrations, the catalytic efficiency of these reproduced triggers was found to play a vital role in the autocatalytic profile and thus could be facilely improved to achieve more efficient and characteristic autocatalytic signal amplification. Due to its exponentially high signal amplification and minimal reaction components, our self-stacking AAC facilitated the efficient detection of trace biomolecules with low signal leakage, thus providing great clinical diagnosis and therapeutic assessment potential.

Background Advanced cancers qualify as severe stressors to family caregivers (FCGs), which can negatively impact caregivers’ psychological and physical well-being because of their association with high symptom burden, distress, and poor prognosis. Objective This review aims to synthesize FCGs’ experiences of caring for advanced cancer patients using a qualitative systematic review method. Methods A comprehensive search was conducted in 7 databases from inception until July 2020. Two reviewers independently screened and assessed each study using Joanna Briggs Institute instruments and subsequently undertook the meta-aggregation approach to synthesize findings. Results A total of 26 studies were included, refined to 37 findings, and integrated into 9 categories and 5 synthesized findings. When a loved one with advanced cancer faced deterioration near the end of their life, FCGs showed a tremendous sense of responsibility for care and concerted great efforts to alleviate their loved one’s suffering while lacking effective professional support. Cultural beliefs had a great impact on FCGs’ responsibility and role recognition. Ultimately, the caregiving helped FCGs achieve personal transcendence inherent in their unique experience. Conclusions Caring for advanced cancer patients is a unique, culture-specific experience marked by struggle. Effective professional support, including early palliative care, should be considered to improve the FCGs’ experience of caring for advanced cancer patients. Cultural beliefs should be considered to understand and develop appropriate strategies to support FCGs. Implications for Practice Healthcare providers need to ensure that individualized, multifaceted interventions considering FCGs’ needs are delivered at the optimal time with the appropriate approach.

Catalytic DNA circuits are desirable for sensitive bioimaging in living cells; yet, it remains a challenge to monitor these intricate signal communications because of the uncontrolled circuitry leakage and insufficient cell selectivity. Herein, a simple yet powerful DNA-repairing enzyme (APE1) activation strategy is introduced to achieve the site-specific exposure of a catalytic DNA circuit for realizing the selectively amplified imaging of intracellular microRNA and robust evaluation of the APE1-involved drug resistance. Specifically, the circuitry reactants are firmly blocked by the enzyme recognition/cleavage site to prevent undesirable off-site circuitry leakage. The caged DNA circuit has no target-sensing activity until its circuitry components are activated via the enzyme-mediated structural reconstitution and finally transduces the amplified fluorescence signal within the miRNA stimulation. The designed DNA circuit demonstrates an enhanced signal-to-background ratio of miRNA assay as compared with the conventional DNA circuit and enables the cancer-cell-selective imaging of miRNA. In addition, it shows robust sensing performance in visualizing the APE1-mediated chemoresistance in living cells, which is anticipated to achieve in-depth clinical diagnosis and chemotherapy research.

Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate molecular self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) in live cells and mice by eliminating undesired off-site signal leakage. The simple and robust DSC system is composed of a primary cell-specific circuitry regulation (CR) module and an ultimate signal-transducing amplifier (SA) module. After the modularly designed DSC system was delivered into target live cells, the DNAzyme of the CR module was site-specifically activated by endogenous demethylase to produce fuel strands for the subsequent miRNA-targeting SA module. Through the on-site and multiply guaranteed molecular recognitions, the lucid yet efficient DSC system realized the reliably amplified in vivo miRNA sensing and enabled the in-depth exploration of the demethylase-involved signal pathway with miRNA in live cells. Our bioorthogonally on-site-activated DSC system represents a universal and versatile biomolecular sensing platform via various demethylase regulations and shows more prospects for more different personalized theragnostics.