Editors-in-Chief

Shu-Min DUAN

Zhi-Hong LIU

ISSN 1673-1581

CN 33-1356/Q

Published by

Zhejiang University Press

2022 JIF 4.7

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  • Editorial

    Jixi ZHANG, Yi ZHANG

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  • Review

    Abstract：Bacterial infections remain a significant threat to public health worldwide, driving an urgent need for rapid, accurate, and field-deployable diagnostic techniques. Point-of-care testing (POCT) has emerged as a transformative strategy, providing timely detection, operational simplicity, and portability. Recent studies have aimed at enhancing sensitivity, specificity, multiplexing capability, and automation through the integration of molecular diagnostics with microfluidics and lab-on-chip technologies, alongside the development of low-cost, portable devices equipped with smartphone-based readout and cloud connectivity for real-time surveillance in resource-limited settings. Nonetheless, evidence-based frameworks for selecting optimal detection targets—such as genomic sequences, conserved protein epitopes, or viable whole cells—and matching them to appropriate POCT modalities remain notably underrepresented in the literature. This review systematically summarizes recent advances in POCT strategies for bacterial detection, categorized according to three major types of detection targets, including cellular phenotypic characteristics, surface antigens, and nucleic acids. We discuss the principles, advantages, limitations, and representative applications of key POCT platforms, which include microscopy-based visualization, immunoassays, isothermal amplification, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) systems, and microfluidic biosensors. Critical challenges, such as sample pretreatment, detection sensitivity, and operational simplicity, have been partially addressed through recent innovations. Finally, we outline the main future research directions focused on the development of integrated, automated, and intelligent POCT systems for clinical deployment.  

    Wen ZHANG, Yundong HANG, Sisi ZHAN, Weiyao SONG, Binxiao LI, Nan CHEN, Min LV

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  • Review

    Abstract：Programmable RNA-cleaving DNAzymes (RCDs) represent a unique class of catalytic nucleic acids that couple molecular recognition with enzyme-like activity. While DNAzymes have traditionally been explored for targeted gene regulation, recent advances in nanotechnology have repositioned them as programmable biosensing modules with stimuli-responsive therapeutic potential. When integrated into metal-oxide scaffolds, DNA-framework architectures, or metal-organic frameworks, DNAzymes form hybrid platforms that create confined catalytic microenvironments, provide enriched cofactor availability, and facilitate microenvironment-responsive activation. These engineered systems can function as nanoscale biosensing modules that respond to pH, redox gradients, metal ions, or microRNA signatures and convert these biological cues into catalytic outputs. Beyond enhancing analytical performance, such platforms may also reshape tumor immunometabolism. Through the selective cleavage of metabolic or immune-regulatory transcripts, DNAzyme nanocatalysts can directly reprogram glycolysis, redox balance, oxygen tension, and mitochondrial activity, and these metabolic changes in turn alleviate immunosuppression and promote innate and adaptive immune activation. This review outlines the mechanistic foundations of DNAzyme catalysis, summarizes recent nanoengineering strategies that endow DNAzymes with programmable sensing and stimuli-responsive functions, and discusses how these systems bridge biosensing and catalytic immunometabolic functions. We conclude with perspectives on translational challenges and opportunities, endorsing programmable DNAzyme nanocatalysts as emerging preclinical platforms for biosensing-guided immunometabolic intervention.  

    Rongping LUO, Zhuojia TANG, Mengqi DING, Lingxiu ZOU, Xiaojing LIU, Fan YIN, Jianxin LYU, Lu WANG

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  • Review

    Abstract：The blood‒brain barrier (BBB) is a vital physiological structure that maintains the microenvironmental homeostasis in the central nervous system (CNS). Imbalances in its permeability play a key role in various neurological disorders, including stroke, neurodegenerative diseases, and brain tumors. The development of precise techniques for assessing BBB permeability is therefore paramount for elucidating the mechanisms of neurological diseases, overcoming drug development challenges, and achieving precise diagnosis and treatment of CNS disorders. This review systematically summarizes the latest advances in the assessment of BBB permeability. Regarding in vitro models, platforms have evolved from the traditional transwell system to microfluidic chips incorporating fluid shear forces and subsequently to highly biomimetic brain organoids, with continuous improvements in the ability to simulate the neurovascular unit (NVU) microenvironment. For in vivo assessment, we detail the principles and applications of imaging techniques, including dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), positron emission tomography (PET), near-infrared II (NIR-II) fluorescence imaging (FI), and two-photon microscopy (TPM), highlighting their complementary strengths in macroscopic quantification, molecular targeting, and microscopic dynamic observation. The integration of multi-modal technologies and precise quantitative assessment is a prominent trend. Future investigations will focus on artificial intelligence (AI)-driven personalized permeability assessment, the development of novel intelligent probes, and the dynamic real-time monitoring of the BBB, thereby providing powerful methodological support for neurological disease research.  

    Miaomiao WANG, Lu GAN, Yiru FAN, Chenxi DUAN, Ying ZHU, Shihua LUO, Yanhong SUN

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  • Review

    Abstract：Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and continues to present significant challenges in early diagnosis, precise subtyping, and prognosis assessment. In recent years, the field of biomarker research has undergone a profound paradigm shift from static concentration measurements to functional activity detection. The most revolutionary breakthrough is the α-synuclein seed amplification assay (α-Syn-SAA), which enables ultrasensitive and specific detection of pathological α-Syn in both clinical and prodromal stages, thus providing an unprecedented window for early intervention. Substantial progress has also been made in the development of biomarkers such as neurofilament light chain (NfL), Alzheimer’s disease-related biomarkers, and genetic biomarkers, as well as in detection technologies based on peripheral samples. The integrated application of cutting-edge technologies, such as real-time quaking-induced conversion (RT-QuIC), high-resolution mass spectrometry, and high-field magnetic resonance imaging (MRI), is advancing the field into a new stage characterized by a focus on pathological activity, multi-omics integration, and non- or minimally invasive approaches. In this review, we explore recent advances in PD biomarkers, focusing on core pathophysiological markers. We examine the potential of multi-omics and artificial intelligence (AI) to enhance diagnostic, subtyping, and prognostic accuracy, while also outlining the pivotal role and future directions of biomarkers in advancing precision medicine for PD.  

    Xiang LI, Honglin CHEN, Xu WANG, Yuhe HU, Zhaofei YANG, Min WEI

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  • Research Article

    Abstract：Circular RNAs (circRNAs) are key post-transcriptional regulators with critical roles in pathogenesis, yet existing tools for their precise manipulation and functional analysis in living cells remain to be developed. A compelling therapeutic target in this field is the circRNA cerebellar degeneration-related protein 1 antisense (CDR1as), functioning as an oncogenic sponge for microRNA-7 (miR-7). Herein, we report a novel multifunctional zeolitic imidazolate framework-8 (ZIF-8)-based nanoplatform for the simultaneous disruption and real-time monitoring of the CDR1as/miR-7 regulatory axis. This system, named DZ/MB@ZIF-8, co-encapsulates a designed set of DNAzymes (DZs) for the catalytic cleavage of CDR1as as well as a molecular beacon (MB) for reporting on miR-7 activity. Following cellular uptake and lysosomal trafficking, the acidic microenvironment triggers nanoplatform disassembly, concurrently releasing the therapeutic and sensing components along with essential Zn2+ cofactors for DZ activation. This system demonstrates efficient CDR1as degradation, which liberates miR-7 and inhibits the expression of its downstream oncogenic targets. Crucially, this therapeutic effect is directly correlated with a turn-on fluorescent signal from the MB, enabling the real-time, live-cell readout of circRNA regulation. This work establishes a versatile theranostic strategy that merges targeted gene regulation with intrinsic biosensing, offering a powerful platform for probing circRNA function and advancing RNA-based therapeutics.  

    Yan HUANG, Jialin YE, Lan XU, Xingjie HU, Nan CHEN

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  • Research Article

    Abstract：Meat adulteration is a significant global food safety challenge, creating a pressing need for rapid and on-site detection technologies. Herein, we present an intelligent one-pot biosensing platform termed one-pot TLAMP-PfAgo assay (OTPA) that integrates the rapid amplification of turn-back loop primer-accelerated loop-mediated isothermal amplification (LAMP) (TLAMP) with the sequence-specific detection of Pyrococcus furiosus Argonaute (PfAgo). This system features a clever heat-activatable design using microcrystalline wax to spatially separate reactions within a single tube, enabling contamination-free and streamlined operation. The OTPA assay achieves sensitive and specific detection, with limits of detection as low as 3×10-4 ng/μL for pork DNA and 2×10-4 ng/μL for beef DNA within 30 min. It successfully enables duplex target identification and has been validated with commercial meat products, showing perfect concordance with standard polymerase chain reaction (PCR)-based qualitative detection. Notably, the result can be directly visualized under blue light, underscoring the substantial potential of this cost-effective and simple platform for point-of-care testing (POCT) and intelligent biosensing in food safety surveillance.  

    Sheng DING, Jing LI, Minglong YANG, Yujia SONG, Xiangke NIU, Mei LI, Yao LUO

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  • Research Article

    Abstract：To elucidate the diagnostic value and clinical relevance of protein kinase D3 (PRKD3) in hepatocellular carcinoma (HCC), we analyzed data retrieved from The Cancer Genome Atlas (TCGA) database, which revealed high expression of PRKD3 in HCC tissues. Subsequently, we collected a total of 392 clinical plasma samples from healthy individuals, patients with cirrhosis or decompensated cirrhosis, and patients with HCC. Plasma PRKD3 levels were then determined across HCC patients and individuals at high risk of developing the disease. The results revealed significantly elevated PRKD3 concentrations in patients with cirrhosis, decompensated cirrhosis, and HCC compared to healthy controls (P<0.01). The areas under the receiver operating characteristic (ROC) curve for these three groups were 0.8107, 0.7899, and 0.7177, respectively. To further evaluate the efficacy of PRKD3 as an adjunctive diagnostic biomarker for HCC, we employed a panel of machine learning algorithms as primary classifiers, including extra trees (ET), gradient boosting (GB), random forest (RF), and support vector machine (SVM). A multi-parameter joint diagnostic model was constructed by combining PRKD3 expression data with a set of clinical parameters, including gender, age, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence-II (PIVKA-II). This integrated approach exhibited substantially improved diagnostic performance, achieving an accuracy of 0.861, sensitivity of 0.863, specificity of 0.925, and precision of 0.862. Collectively, these findings highlight the potential of PRKD3 as an integral component of a comprehensive diagnostic tool for the early identification of HCC.  

    Jing LI, Yifan ZHAO, Yicheng MA, Bei XIE, Li HUANG, Haitang YANG, Xingyuan MA, Haohua DENG, Shuaiyang WANG, Chanjuan SUN, Pengfei CAO, Linjing LI

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