Advanced Science
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2025
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IF 14.1
Shuai Wu,Yincheng Liu,Tianyu Zeng,Tianci Zhou,Yanting Sun,Ying Deng,Juan Zhang,Genxi Li,Yongmei Yin
Continued development of clustered regularly interspaced short palindromic repeats (CRISPR)-powered biosensing system on the electrochemical interface is vital for accurate and timely diagnosis in clinical practice. Herein, an electrochemical biosensor based on manganese metal-organic frameworks (MOFs)-enhanced CRISPR (MME-CRISPR) is proposed that enables the efficient detection of circulating tumor DNA (ctDNA). In this design, customized enzyme stimulants (Mn 2+ ) are co-assembled with Cas12a/crRNA to form enzyme-MOF composites, which can be released quickly under mild conditions. The MOFs-induced proximity effect can continuously provide adequate Mn 2+ to sufficiently interact with Cas12a/crRNA during the release process, enhancing the trans-cleavage activity of complex available for biosensor construction. The MOFs-based enzyme biocomposites also afford efficient protection against various external stimulus. It is demonstrated that the developed biosensor can achieve ultrasensitive detection of epidermal growth factor receptor L858R mutation in ctDNA with a low detection limit of 0.28 f m without pre-amplification. Furthermore, the engineered mismatch crRNA enables the biosensor based on MME-CRISPR to detect single nucleotide variant with a high signal-to-noise ratio. More importantly, it has been successfully used to detect the targets in clinical practice, requiring low-dose samples and a short time. This strategy is believed to shed new light on the applications of cancer diagnosis, treatment, and surveillance.
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高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Jing Peng,Simin Liu,Ziyue Qiu,Luyin Zhang,Ziyan Dong,Qianying Zhou,Ting Huang,Yanfei Zhang,Jingyu Shi,Jin-Xiang Chen,Zong Dai,Jun Chen
miRNA is an effective disease diagnostic biomarker. Developing efficient miRNA in living cells analysis methods, holds significant importance for disease diagnosis and understanding disease progression. Strategies combining DNA nanostructures and enzyme-free amplification have been developed for highly sensitive and rapid imaging of miRNA. However, due to nonspecific amplification of enzyme-free amplification inherent in the probe assembly process and during transfection, these strategies suffer from significant background signals and reduced sensitivity, limiting their further application. To overcome these limitations, we have developed a DNA tetrahedral-based and photocontrolled intramolecular CHA strategy (TCHA-P) to achieve spatiotemporal, highly sensitive, and accurate imaging of miRNA in living cells. In this strategy, the DNA tetrahedron not only serves as a transfection vector but also enhances the local concentration of reactant probes, boosting the reaction kinetics and sensitivity of CHA. Additionally, the light-controlled group (PC-linker) can trigger CHA at selected times and locations, enhancing the spatiotemporal precision of miRNA imaging and ensuring high sensitivity and accuracy by eliminating nonspecific amplification during the assembly and transfection processes. Using miR-10b as a proof-of-concept model, the proposed strategy demonstrated higher signal-to-noise ratio compared to traditional CHA, with a detection limit of 28 pM. Living cell imaging experiments showed that the strategy could effectively differentiate the expression of miR-10b between normal breast cells and breast cancer cells, providing high imaging contrast. The strategy holds promise for broadening the path of nucleic acid amplification-based imaging and is expected to become an effective tool in nucleic acid-based disease diagnosis, treatment, and drug development.
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BIOSENSORS & BIOELECTRONICS
·
2022
·
IF 12.545
Jialin Zhang,Yaqi Fan,Jinhui Li,Bin Huang,Herui Wen,Jiali Ren
The key factor to control the incidence rate of diseases caused by bacteria is rapid detection and early diagnosis. Herein, we proposed a new electrochemical bacterial sensor by coupling DNA walking and rolling circle amplification (RCA) reaction-assisted “silver-link” crossing electrode. Staphylococcus aureus ( S. aureus ) was detected using this proof-of concept strategy. Aptamer/DNA walker and auxiliary sequence (AS)/RCA reaction probe (RP) duplexes were modified on the electrode surface . The binding of S. aureus with its aptamer caused the disintegration of aptamer/DNA walker and released DNA walker. With the help of Exo III, DNA walker moved along the electrode surface and AS in AS/RP duplex was continuously digested to release RP. By introducing phi29 DNA polymerase, RCA reaction was performed using RP as the reaction primer to form long single-strand RCA extension products between the electrodes. The “silver-link” crossing electrode was formed by metallization of “gene-link”, significant conductivity was thus acquired for bacteria detection . The limit of detection (LOD) was 10 CFU/mL and detection time was 2 h. The proposed sensor has high efficiency, good stability and low background signal, human serum and milk samples were successfully detected, which emerged a promising potential in the food monitoring and clinical diagnosis.
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MEDICINAL CHEMISTRY RESEARCH
·
2023
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IF 2.6
Long Xing,Yang Peilin,Chen Lin,Zhong Wen,Chen Shaofeng,Li Yanping,Lin Shijie,Tian Wei
Oral cancer severely affects the quality of life of patients, and the primary treatment is surgery, due to a lack of specific drugs. Aloe emodin, a natural product of anthraquinone, is considered a potential antitumor drug. However, it has poor water solubility and low biological activity. In this study, we designed and synthesized a novel aloe emodin–hydroxyethyl piperazine hybrid dihydrochloride ( AE-NPC ), which improved the water solubility and antitumor activity of aloe emodin in vitro. According to the results, the IC 50 value of AE-NPC on CAL-27 cancer cells was 14.4 ± 2.9 μM. The flow cytometry results showed that AE-NPC induced the production of reactive oxygen species (ROS) and apoptosis in CAL-27 cells. The spectroscopy and molecular docking results showed that AE-NPC can be well intercalated into DNA grooves. Further molecular mechanism studies revealed that AE-NPC not only regulates the expression levels of key proteins (Bax/Bcl-2, cytochrome C, cleaved caspase-9 and cleaved caspase-3) of the mitochondrial apoptotic pathway but also activates the expression levels of a key protein ( γ -H 2 AX) of the DNA damage pathway. Therefore, AE-NPC induces CAL-27 cell apoptosis via DNA damage and mitochondrial pathways. This study provides new insights into the further development of anthraquinone compounds as potential chemotherapeutic agents for oral cancer treatment.
The novel aloe emodin derivative AE-NPC induces oral cancer CAL-27 cells apoptosis through ROS production, DNA damage and mitochondrial pathways. The anthraquinone compound AE-NPC may be a potential agent for the treatment of oral cancer.
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PHYTOMEDICINE
·
2021
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IF 5.34
Lei Yu,Shuang Han,Lang Lang,Hui Song,CaiYun Zhang,Lin Dong,ShaoHua Jia,Ying Zhang,Di Xiao,Jun Liu,Ying Xu,XiaoPo Zhang
Background DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong ( S. hainanensis ), a Li nationality plant that has abundant aporphine alkaloids , can inhibit Topo. Purpose To identify a dual Topo inhibitor , a deep and systematic study of active aporphine alkaloids in S. hainanensis and their mechanisms of inhibiting breast cancer proliferation and Topo activity are essential. Study design This study aimed to assess the anti-breast cancer and Topo inhibitory activities of oxocrebanine and explore the underlying mechanisms. Methods The growth inhibitory activities of 12 compounds in S. hainanensis were screened by MTT assay in MCF-7, SGC-7901, HepG-2 cells, and compared with the effects on human normal mammary epithelial MCF-10A cells as non cancer control cells. The Topo inhibitory activity was assessed by DNA relaxation and unwinding assays, kDNA decatenation assay and western blot . Cell cycle and autophagy analyses were carried out with flow cytometry and staining. Acridine orange staining and α-tubulin morphology were observed by fluorescence microscopy . Western blot was used to examine microtubule assembly dynamics and the expression levels of key proteins associated with DNA damage, autophagy and mitotic arrest . Results Oxocrebanine was the anti-breast cancer active alkaloid in S. hainanensis . It exhibited the best inhibitory effect on MCF-7 cells with an IC 50 of 16.66 μmol/l, and had only weak effect on the proliferation of MCF-10A cells. Oxocrebanine inhibited Topo I and II α in a cell-free system and in MCF-7 cells. The DNA unwinding assay suggested that oxocrebanine intercalated with DNA as a catalytic inhibitor. Oxocrebanine regulated the levels of Topo I and IIα and DNA damage-related proteins. Oxocrebanine led to the mitotic arrest, and these effects occurred through both p53-dependent and p53-independent pathways. Oxocrebanine induced autophagy, abnormal α-tubulin morphology and stimulated enhanced microtubule dynamics. Conclusion Oxocrebanine was the anti-breast cancer active aporphine alkaloid in S. hainanensis . Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator . Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.
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高影响因子
Foods
·
2026
·Vol. 15
·期 20
·3718
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IF 6
Yimiao Xia,Mengru Guo,Shengwen Cui,Boye Liu,Yu Chen,Fusheng Chen
Soybean is the most widely cultivated genetically modified (GM) crop worldwide, making the detection of GM soybean oil a critical issue for food safety and trade compliance. Such detection depends on whether DNA survives oil processing, yet how processing affects DNA in refined oil has remained unclear. Here, we tracked DNA mass and gene integrity along a complete industrial soybean oil processing chain, from seed to deodorized oil, and compared three degumming methods at laboratory scale. DNA mass dropped sharply during crude oil extraction and degumming, the larger part of the loss occurring between the meal and the crude oil, leaving refined oils with extremely low levels (2.60 × 10−2to 7.43 × 10−1ng/g). During degumming, most DNA moved from crude oil into the oil sediment, with removal efficiency decreasing in the order enzymatic > acid > hydration degumming, in line with phospholipid removal. Thelectinandcp4 epspsgenes degraded mainly during solvent extraction and deodorization. These findings reveal where GM DNA is lost or destroyed along the chain, show that fragments below 200 bp survive to fully refined oil, and identify enzymatic degumming as the most effective treatment for removing DNA (at the lab scale). Testing of refined soybean oil therefore requires short amplicons, and a negative result obtained with longer targets does not demonstrate the absence of GM material.
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JOURNAL OF FLUORESCENCE
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2026
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IF 3.4
Liang Tianmi,Liu Shijian,Ma Wenjin,Tao Xiaoqi
Colla Corii Asini ( CCA ), a traditional food-medicine product, is vulnerable to food safety and market integrity due to frequent adulteration. This study developed a lateral flow assay based on polyethylenimine-functionalized europium metal-organic frameworks (PEI-Eu-MOFs-LFA) for quantitatively detecting donkey DNA to assess the authenticity of CCA , without the need for knowing the types of adulterants. The protonated amino groups on the PEI‑Eu-MOFs surface formed stable complexes with negatively charged single‑stranded DNA (ssDNA) probes. Electrostatic attraction and hydrogen bonding facilitated conjugate formation, leading to fluorescence quenching of the PEI-Eu-MOFs via the inner-filter effect (IFE). This method enables direct analysis after DNA extraction, eliminating the need for additional nucleic acid amplification steps, and completes the entire process in just 60 min. Furthermore, a calibration curve was established between the T/C ratio and the logarithmic value of donkey hide content (2% to 100%). The PEI-Eu-MOFs-LFA exhibited excellent sensitivity and accuracy, with a detection limit of 1.86%, recoveries ranging from 85.70% to 114.63%, and relative standard deviations from 2.48% to 12.59%. Consequently, PEI-Eu-MOFs-LFA demonstrates high sensitivity and accuracy, significantly improving detection efficiency and providing an innovative approach for quality control and market regulation of CCA .
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CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Yu Chen,Shujing Wang,Xiran Zhou,Yu Cheng,Jiahao Liang,Shengjun Cheng,Dongmei Tong,Hongyu Xiang,Xianda Liu,Tinghang Yang,Yupei Li,Weifeng Zhao,Changsheng Zhao
Circulating histones are critical inflammatory mediators that drive hyperinflammation and organ failure in critical illnesses such as sepsis, acute kidney injury, and acute respiratory distress syndrome. Their plasma levels are significantly correlated with disease severity and mortality in such patients. Although both DNA and sulfonic acid-containing macromolecules bind histones via electrostatic interactions, the primary challenge in integrating these antagonists into a unified anti-histone system lies in their mutual water solubility and similar negative charges. Herein, we fabricate novel chitosan/DNA-poly(sodium-4-styrenesulfonate) porous microspheres (C3D1-PSS) by employing a stepwise strategy involving phase inversion and subsequent in situ crosslinking polymerization. With a high-density, negatively charged histone capture network, the C3D1-PSS microspheres exhibit excellent hemocompatibility and achieve a notable histone adsorption ratio of 86.47% within 2 h and 95.52% within 4 h through synergistic electrostatic interactions mediated by phosphate and sulfonate groups in vitro. Furthermore, the C3D1-PSS microspheres significantly mitigate histone-induced thrombocytopenia, platelet activation, hemolysis, cytokine release, and endothelial cell death. In a histone-induced rabbit sepsis model, the C3D1-PSS microspheres efficiently alleviate histone-induced thrombocytopenia, tissue damage, hyperinflammation, and cell apoptosis. Collectively, this work presents a promising adsorbent for extracorporeal removal of histones and holds potential for managing histone-associated critical illnesses.
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ARCHIVES OF TOXICOLOGY
·
2026
·
IF 10.9
Sun Haiting,Chen Manxin,Zhu Shunda,Xu Ke,Wang Yujian,Liu Yungang
Carbamazepine is a commonly applied anti-neurosis drug, which meanwhile severely pollutes the global environment. It induced DNA/chromosome damage and gene mutations in vitro following metabolic activation, however, evidence for its genotoxicity in intact mammalians remains absent. In this study, 6-week old male C57BL/6J mice were exposed to carbamazepine by gastric gavage at doses of 8, 20, and 50 mg/kg/d for 7 consecutive days, followed by a micronucleus test in bone marrow polychromatic erythrocytes, a comet assay in hepatocytes, and Western blot assay of hepatic proteins, including a phosphorylated histone 2AX (γ-H2AX, indicator of double-strand DNA breaks), aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), and several Cyp enzymes. In some experiments, ticlopidine (4 mg/kg/d, specific inhibitor of Cyp2b) was used as a modulator. The results demonstrated no obvious toxicity of carbamazepine to the liver or bone marrow, while it induced micronucleus formation in the bone marrow and hepatic DNA damage (indicated by positive comet assay results and elevated γ-H2AX protein) at 20 and/or 50 mg/kg/d doses, all of which were nevertheless abolished or alleviated by ticlopidine. Meanwhile, carbamazepine induced hepatic AhR and CAR at 50 mg/kg/d, and PXR, Cyp2b10 and Cyp3a11 at doses ≥ 20 mg/kg/d, with no effect on Cyp1a2; furthermore, coexposure of ticlopidine blocked the induction of PXR, Cyp3a11 and Cyp2b10 by carbamazepine, while enhanced that of AhR. This study provides evidence for the genotoxicity of carbamazepine in mammalians in vivo, its dependence on Cyp2b activity, and the activation of relevant nuclear receptor/Cyp-regulating pathway.
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MICROCHEMICAL JOURNAL
·
2026
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IF 5.2
Shunbi Xie,Can Huang,Yue Fu,Dicai Chen,Wantong Si,Linlei Liu
Aptamer combined with DNA walker and ALP enables sensitive indirect detection of BPA. • Brilliant green binds molybdophosphoric acid to generate yellow-green color shifts. • Three modes (UV–Vis, RGB, swab sensor) satisfy lab, field and house testing demands. Bisphenol A (BPA) is a ubiquitous contaminant prevalent in food and environmental matrices. Herein, a smartphone-assisted multichannel colorimetric biosensor for BPA detection is constructed by integrating BPA aptamer-activated DNA walker, alkaline phosphatase (ALP)-catalyzed hydrolysis, and the molybdophosphoric acid assay. The DNA walker is immobilized on magnetic beads through biotin-streptavidin interaction, which enables target-triggered DNAzyme release and cyclic cleavage reactions. This autonomous cyclic amplification process efficiently releases substantial ALP into the supernatant. The liberated ALP further catalyzes the hydrolysis of 4-nitrophenyl phosphate (4-NPP) to produce phosphate ions (Pi), which react with ammonium molybdate under acidic conditions to form 12-molybdophosphoric acid (12-MPA). The introduction of brilliant green (BG) induces a distinct solution color transition from yellow to green, and the color variation exhibits a positive correlation with BPA concentration. Based on the above sensing mechanism, three versatile detection modes are established, including laboratory-grade UV–Vis spectrophotometry, smartphone-based RGB colorimetry, and a portable cotton swab sensor. The proposed biosensor displays superior selectivity against BPA structural analogs, excellent reproducibility, and satisfactory spiked recovery in real milk sample detection. Leveraging low-cost commercial commodities (cotton swabs and smartphones) and cascaded signal amplification strategy, this work provides a cost-effective, user-friendly, and multi-scenario adaptable platform for BPA detection. Download: Download high-res image (148KB) Download: Download full-size image
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ACS Sensors
·
2026
·
IF 10.9
Jingzhe Zang,Yingyu Zhang,Kangbo Liu,Yuyin Xu,Liang Zhao,Wentao Wang,Mengxin Zhang,Xueyi Qin,Qionglin Wang,Xianwei Zhang,Wancun Zhang
Our previous study demonstrated that apurinic/apyrimidinic endonuclease 1 (APE1) and miR-514a are significantly overexpressed in the cytoplasm of drug-resistant neuroblastoma (NB) cells. Furthermore, we have developed a novel strategy for monitoring drug resistance in NB by targeting cytoplasmic APE1 and miR-514a. The overexpression of key enzymes in the mitochondrial base excision repair pathway, along with dysregulated miRNAs, is closely associated with chemotherapy resistance in tumors. Therefore, this study leverages cytochrome c (cyt c), located in the inner mitochondrial membrane as a targeting agent and the mitochondria-specific expression of 16S rRNA as a response switch to develop a spatially resolved, sequential activation system for an allosteric DNA nanomachine (AP-miR-tFNA), enabling in vivo detection of APE1 and miR-514a within mitochondria and facilitating molecular imaging of NB. AP-miR-tFNA sequentially responds to cyt c, 16S rRNA, miR-514a, and APE1, thereby undergoing a conformational change that efficiently achieves progressive dissociation of the fluorophore from the quencher through a sequential mechanism, ultimately generating a detectable fluorescence signal. Experimental results demonstrate that AP-miR-tFNA enables in vivo monitoring of drug resistance in NB, providing an innovative and dependable approach for monitoring therapeutic resistance in NB. In particular, AP-miR-tFNA enables in situ detection of APE1 and miR-514a within NB plasma exosomes, thereby allowing non-invasive differentiation between high-risk and low-to-intermediate-risk NB, as well as between drug-resistant NB and non-drug-resistant NB.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2026
·
IF 8.3
Wanyi Xiong,Shunbi Xie,Youlin Tang,Runzi Zhang,Xiaoyu Yang,Yi He
Lomefloxacin (LOM) residues in food can induce bacterial resistance and pose serious health risks. Therefore, sensitive detection of trace LOM is of great significance. A recyclable and degradable surface-enhanced Raman scattering (SERS) biosensor, which is based on stimuli-responsive DNA/covalent organic frameworks (COF) and cellulose hydrogel (CA-β-CD), was developed for the ultrasensitive detection of LOM. Specifically, by utilizing the high adsorption capacity of COF, a large number of Raman-active signal molecules (methylene blue, MB) were incorporated to form a stimuli-responsive DNA/COF complex that responds to the LOM. Subsequently, a recyclable SERS substrate was fabricated through the integration of cyclodextrin-functionalized cellulose gel (CA-β-CD) with green leaf@Ag NPs. Upon exposure to the target, LOM competitively bound to the aptamer, triggering the release of MB, which was then captured through host-guest interactions by the CA-β-CD, thereby generating a strong SERS signal. The immobilized MB can be desorbed by modulating the pH, which enables the efficient regeneration and reuse of the SERS substrate. Furthermore, the cellulose gel can be degraded in the presence of cellulase, ensuring an environmentally sustainable detection approach. The proposed method achieved ultrasensitive detection of LOM over a linear range of 1.0 × 10 −11 to 1.0 × 10 −5 mol/L, with a detection limit as low as 3.56 × 10 −12 mol/L. Moreover, the biosensor demonstrated outstanding specificity and robustness in the face of potential interferents and has been successfully applied to the analysis of real-world samples. This work offers a novel and reliable strategy for the sensitive detection of antibiotics in food matrices.
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危险品化学品经营许可证（带存储）