MICROCHEMICAL JOURNAL
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2025
·
IF 5.1
Haohao Chen,Min Yuan,Fengqin Yin,Hui Cao,Xiuxiu Wu,Liling Hao,Weiyan Shi,Tai Ye,Fei Xu
The traditional nucleic acid-modified electrode in room-temperature manner suffers from the drawback of time-consuming and uneven distribution. In this work, we adopted the freeze-thawing method to construct a nicking enzyme-powered DNA walking machine on the gold electrode. In the absence of kanamycin, the intact substrate strand can trigger the self-assembly and form G4 nanowires on the electrode surface. After adding hemin, a significant catalytic current of the TMB oxidization can be observed. By contrast, once the specific binding between aptamer and kanamycin occurs, the activated walking strand processes a consecutive binding-cleavage cycle with the substrate strand on the electrode surface. The residue substrate fragment is unable to trigger the subsequent G-quadruplex assembly, resulting in a decrease in catalytic current. Under optimal experimental conditions, a linear relationship between the kanamycin concentration and current decrease was obtained in the range from 5 to 100 pM, and the limit of detection was 1.44 pM. This method has also demonstrated practical performance in the spiked milk and honey with satisfactory recoveries of 107.1 % to 114.3 % and 94.3 % to 101.5 %, respectively.
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高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Xinlu,Gong Luyao,Wang Yuanyuan,Ye Chen,Guo Huanhuan,Gao Shen,Chen Jiyuan,Wang Zhuo,Gao Yuan
Introduction: Metastatic castration-resistant prostate cancer (mCRPC) patients face challenges due to limited treatment options. About 50% of patients with mCRPC have a functional loss of phosphatase and tensin homology deleted on chromosome 10 (PTEN), leading to tumor progression, metastasis, and immune suppression. Moreover, elevated IL-23 produced by myeloid-derived suppressor cells (MDSCs) is found in CRPC patients, driving tumor progression. Therefore, a combination strategy based on PTEN restoration and IL-23 inhibition may block CRPC progression and metastasis.Methods: The antitumor effect of restoring PTEN expression combined with the IL-23 inhibitor Apilimod was studied in a mouse model of bone metastasis CRPC and mouse prostate cancer RM-1 cells. To verify the targeting ability of PTEN DNA coated with lipid nanoparticles (LNP@PTEN) in vitro and in vivo. In addition, RT-qPCR and flow cytometry were used to investigate the related mechanisms of the antitumor effect of LNP@PTEN combined with Apilimod.Results: LNPs exhibited significant tumor-targeting and tumor accumulation capabilities both in vitro and in vivo, enhancing PTEN expression and therapeutic efficacy. Additionally, the combination of LNP@PTEN with the IL-23 inhibitor Apilimod demonstrated enhanced inhibition of tumor growth, invasion, and metastasis (particularly secondary organ metastasis) compared to other groups, and extended the survival of mice to 41 days, providing a degree of bone protection. These effects may be attributed to the PTEN function restoration combined with IL-23 inhibition, which help reverse immune suppression in the tumor microenvironment by reducing MDSCs recruitment and increasing the CD8+/CD4+ T cell ratio.Discussion: In summary, these findings highlight the potential of LNPs for delivering gene therapeutic agents. And the combination of LNP@PTEN with Apilimod could achieve anti-tumor effects and improve tumor microenvironment. This combinational strategy opens new avenues for the treatment of mCRPC.
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高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
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2025
·
IF 4.3
Fan Yanan,An Caizhelin,Wang Zhihui,Luo Jia,Wang Wenbin,Luo Qing,Song Guanbin
Hepatocytes are the primary functional cells in the liver, and the malignant transformation of hepatocytes significantly contributes to hepatocellular carcinoma (HCC) progression. Liver fibrosis and cirrhosis caused by extracellular matrix (ECM) remodeling during liver lesions is a pivotal driver of HCC. However, the impact of matrix stiffness on hepatocytes and the underlying molecular mechanisms are not fully understood. Herein, using gelatin/sodium alginate hydrogels with different stiffnesses to simulate the change of matrix stiffness during liver lesions, we found that matrix stiffening leads to a notable decrease in the expression of hepatocyte nuclear factor 4α (HNF4α) and functional hepatocyte genes and a significant increase in the expression of interleukin 6 (IL‒6) in human hepatocyte line L‒02 cells, indicating obvious damage of hepatocyte function. In addition, matrix stiffening causes extensive DNA damage to L‒02 cells. Mechanistically, matrix stiffening upregulates piezo‒type mechanosensitive ion channel component 1 (Piezo1) expression and activates extracellular signal‒regulated kinase 1/2 (ERK1/2) signaling. Piezo1 knockdown suppresses matrix stiffening‒induced functional impairment and DNA damage in L‒02 cells. Moreover, Piezo1 knockdown blocks matrix stiffening‒activated ERK1/2 signaling in L‒02 cells. U0126 (a selective inhibitor of ERK1/2 activation) treatment could rescue matrix stiffening‒induced functional impairment and DNA damage. Taken together, these findings demonstrate that matrix stiffening induces functional impairment and DNA damage in L‒02 cells via the Piezo1‒ERK1/2 signaling pathway, which provides evidence for a better understanding of the hepatocyte function damage caused by tissue mechanical microenvironment change in liver diseases and the mechanotransduction in this process. Graphical abstract An increase in matrix stiffness inhibits HNF4α expression and promotes IL‒6 expression in L‒02 cells. Meanwhile, matrix stiffening induces L‒02 cell DNA damage and upregulates the expression of γ‒H2AX and 53BP1. These findings prove that matrix stiffness is a crucial mechanical regulator of cellular functional impairment and DNA damage and plays an important role in liver disease.
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高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jilong Wang,Chenghu Wu,Yiran Wang,Yecheng Shen,Kerui Wu,Yikai Shi,Tianshou Cao,Shanshan Yuan,Yuting Zhu,Yongheng Bai,Jinhai Huang,Yan Zhang,Junjie Deng
Low-expression antigens, especially neoantigens, pose a significant challenge in immunotherapy for low immunogenicity pancreatic cancer. Increasing the tumor mutation burden is crucial to enhance the expression of tumor antigens and improve tumor immunogenicity. However, the incomplete intervention in DNA stability hampers effective elevation of the tumor mutation burden, thus reducing the probability of neoantigen. To address this issue, we have developed a novel nano-regulator that intervenes in the DNA stability of tumor cells, thereby enhancing tumor mutations. This nano-regulator comprises metal-organic frameworks (MOFs) encapsulating DNA damage agent doxorubicin and DNA damage repair inhibitor siRNA-ATR, enabling simultaneous induction of DNA mutations and inhibition of their repair. Importantly, this regulator, named as MOF DOX&siATR , can modulate the tumor gene expression profile, induce the production of neoantigens of Atp8b1, and enhance the immunogenicity of pancreatic cancer. The characteristics of DNA stability intervention by MOF DOX&siATR hold promise for augmenting the immune response in low immunogenic tumors, making it a potential nanomedicine for the treatment of pancreatic cancer.
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高影响因子
FEBS Journal
·
2024
·
IF 5.5
Wanyi Chen,Binbin Chen,Xinjia Li,Gang Xu,Lirong Yang,Jianping Wu,Haoran Yu
Responsible for synthesizing the complementary strand of the DNA template, DNA polymerase is a crucial enzyme in DNA replication, recombination and repair. A highly conserved tyrosine (Tyr), located at the C-terminus of the O-helix in family A DNA polymerases, plays a critical role in enzyme activity and fidelity. Here, we combined the technology of genetic code extension to incorporate non-canonical amino acids and molecular dynamics (MD) simulations to uncover the mechanisms by which Tyr671 impacts substrate binding and conformation transitions in a DNA polymerase from Thermus aquaticus . Five non-canonical amino acids, namely l -3,4-dihydroxyphenylalanine ( l -DOPA), p -aminophenylalanine ( p AF), p -acetylphenylalanine ( p AcF), p -cyanophenylalanine ( p CNF) and p -nitrophenylalanine ( p NTF), were individually incorporated at position 671. Strikingly, Y671 p AF and Y671DOPA were active, but with lower activity compared to Y671F and wild-type. Y671 p AF showed a higher fidelity than the Y671F, despite both possessing lower fidelity than the wild-type. Metadynamics and long-timescale MD simulations were carried out to probe the role of mutations in affecting protein structure, including open conformation, open-to-closed conformation transition, closed conformation, and closed-to-open conformation transition. The MD simulations clearly revealed that the size of the 671 amino acid residue and interactions with substrate or nearby residues were critical for Tyr671 to determine enzyme activity and fidelity.
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高影响因子
Chemosensors
·
2025
·Vol. 13
·期 2
·32
·
IF 3.7
Yang Dai,Xiuran Mao,Maimaiti A. Abulaiti,Qianyu Wang,Zhihao Bai,Yifeng Ding,Shuangcan Zhai,Yang Pan,Yue Zhang
Monitoring of immune factors, including interferon-gamma (IFN-γ), holds great importance for understanding immune responses and disease diagnosis. Wearable sensors enable continuous and non-invasive detection of immune markers in sweat, drawing significant attention to their potential in real-time health monitoring and personalized medicine. Among these, electrochemical sensors are particularly advantageous, due to their excellent signal responsiveness, cost-effectiveness, miniaturization, and broad applicability, making them ideal for constructing wearable sweat sensors. In this study, we present a flexible and sensitive wearable platform for the detection of IFN-γ, utilizing a DNA hydrogel with favorable loading performance and sample collection capability, and the application of mobile software achieves immediate data analysis and processing. This platform integrates three-dimensional DNA hydrogel functionalized with IFN-γ-specific aptamers for precise target recognition and efficient sweat collection. Signal amplification is achieved through target-triggered catalytic hairpin assembly (CHA), with DNA hairpins remarkably enhancing sensitivity. Ferrocene-labeled reporting strands immobilized on a screen-printed carbon electrode are displayed via CHA-mediated strand displacement, leading to a measurable reduction in electrical signals. These changes are transmitted to a custom-developed mobile application via a portable electrochemical workstation for real-time data analysis and recording. This wearable sensor platform combines the specificity of DNA aptamers, advanced signal amplification, and the convenience of mobile data processing. It offers a high-sensitivity approach to detecting low-abundance targets in sweat, paving the way for new applications in point-of-care diagnostics and wearable health monitoring.
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高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Hongjian Liao,Yuchao Cao,Can Hu,Shangfeng Shen,Zhifei Zhang,Dairong Li,Yonghong Du
Lung cancer is the deadliest kind of cancer in the world, and the hypoxic tumor microenvironment can significantly lower the sensitivity of chemotherapeutic drugs and limit the efficacy of different therapeutic approaches. In order to overcome these problems, we have designed a drug-loaded targeted DNA nanoflowers encoding AS1411 aptamer and encapsulating chemotherapeutic drug doxorubicin and oxygen-producing drug horseradish peroxidase (DOX/HRP-DFs). These nanoflowers can release drugs in response to acidic tumor microenvironment and alleviate tumor tissue hypoxia, enhancing the therapeutic effects of chemotherapy synergistic with sonodynamic therapy. Owing to the encoded drug-loading sequence, the doxorubicin loading rate of DNA nanoflowers reached 73.24 ± 3.45%, and the drug could be released quickly by disintegrating in an acidic environment. Furthermore, the AS1411 aptamer endowed DNA nanoflowers with exceptional tumor targeting properties, which increased the concentration of chemotherapeutic drug doxorubicin in tumor cells. It is noteworthy that both in vitro and in vivo experiments demonstrated DNA nanoflowers could considerably improve the hypoxia of tumor cells, which enabled the generation of sufficient reactive oxygen species in combination with ultrasound, significantly enhancing the therapeutic effect of sonodynamic therapy and evidently inhibiting tumor growth and metastasis. Overall, this DNA nanoflowers delivery system offers a promising approach for treating lung cancer.
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高影响因子
TRANSITION METAL CHEMISTRY
·
2018
·Vol. 43
·期 3
·259-271
·
IF 1.261
Liu Ya-Xian,Mo Hui-Wen,Lv Zhen-Yu,Shen Fang,Zhang Chun-Lian,Qi Yong-Yu,Mao Zong-Wan,Le Xue-Yi
A copper complex [Cu(HPBM)( l -Phe)(H 2 O)]·ClO 4 (1) (HPBM = 5-methyl-2-(2′-pyridyl)benzimidazole, l -Phe = l -phenylalanine anion) was synthesized and characterized by elemental analysis, IR, ESI–MS, HR–ESI–MS, ESR spectroscopy, and by X-ray single-crystal analysis. The binding constant of the complex with calf thymus DNA (CT-DNA) was determined as 7.38 (± 0.57) × 10 4 M −1 . Further studies indicated that the complex interacts with CT-DNA through minor groove binding. The in vitro cytotoxic activities of both the free proligand and the complex against Eca-109, HeLa and A549 cancer cells and normal LO2 cells were evaluated by the MTT method. The IC 50 values range from 5.7 ± 0.1 to 8.3 ± 0.6 µM. Free HPBM displays no cytotoxic activity against the selected cancer cells, with IC 50 values more than 100 µM. Double staining analysis showed that the complex can induce apoptosis in Eca-109 cells. Comet assays demonstrated that the complex can damage DNA and cause apoptosis. The complex also induces an increase in intracellular reactive oxygen species and a reduction in mitochondrial membrane potential. The complex can also increase the intracellular Ca 2+ level and induce release of cytochrome c . The cell cycle arrest was investigated by flow cytometry. The results demonstrate that the complex induces apoptosis in Eca-109 cells through DNA-binding and ROS-mediated mitochondrial dysfunctional pathways.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2018
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IF 2.829
Boyi Niu,Yixian Zhou,Ting Wen,Guilan Quan,Vikramjeet Singh,Xin Pan,Chuanbin Wu
Packaging enough genetic materials is necessary for gene delivery, but functional modification of the carriers may affect their gene loading capacity. In this study, RGD peptide-modified mesoporous silica nanoparticles were synthesized to investigate the influences of functionalization on their DNA adsorption and desorption behaviors. Effects of the functionalization degree of the nanocarriers and the adsorption conditions including DNA concentration, pH, ionic strength and temperature were studied. The DNA adsorption of the nanocarriers were enhanced by reducing pH or adding moderate amounts of ionic salt. Compared with nonfunctional nanoparticles, nanoparticles with low degree of functionalization possessed decreased DNA adsorption capacity but increased adsorption stability. High degree of functionalization resulted in both poor adsorption capacity and stability. Systematic studies showed that the adsorption processes were spontaneous and endothermic, and could be well described by pseudo-second-order kinetic model , Langmuir and Freundlich models. In summary, the DNA loading capacity of mesoporous silica nanoparticles can be improved by proper functionalization and optimized adsorption conditions.
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JOURNAL OF LUMINESCENCE
·
2018
·
IF 2.732
Ziyue Ni,Ting Ye,Yali Yu,Longlong Gao,Yifan Fei,Qiusha Li,Yufeng Zhou,Yong Shao,Lintao Zeng
DNA apurinic/apyrimidinic site (AP site) has received much attention due to its importance in disease evolution and development of selective genetic drugs. Fluorescence technique has been widely employed in identifying the AP sequence environment using fluorophores as the AP site-targeting probes. However, the sequence effect on the AP site binding of a ligand should be fully understood for illustrating the binding behavior. Triplex-forming oligonucleotide (TFO) can bind with its partner ds-DNA via specific hydrogen bonding interactions different from the canonical Watson-Crick pattern to form a triplex DNA structure . Due to its wide bioactivity, triplex has been recently investigated using small molecules as the structure identifiers and tuners. In this work, we spectroscopically characterized a novel fluorescent benz[ e ]indolium probe of BIFS and found that BIFS can selectively target the AP site and its fluorescence is significantly enhanced only when the TFO strand binds to the AP site-containing duplex DNA. The TFO binding restricts the non-radiative twist relaxation process of the excited state BIFS and results in the emissive BIFS. Because BIFS alone in aqueous solution is non-fluorescent, this selective lighting-up emission is advantageous for developing a practical sensor to target the triplex AP site with a weak fluorescence background. This selective recognition of the AP site by the lighting-up fluorescent probe would find wide applications including fluorescently evaluating the triplex-based small molecular binders.
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高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Nana Sun,Yuan Ding,Zhexuan Tao,Hongjie You,Xiude Hua,Minghua Wang
An upconversion fluorescence DNA probe which consists of aptamer-conjugated magnet nanoparticles (apt-MNPs) and complementary DNA-conjugated upconversion nanoparticles (cDNA-UCNPs) was developed to detect acetamiprid. Acetamiprid can specifically conjugate with the apt-MNPs to dissociate the cDNA-UCNPs from the apt-MNPs and resulted in reduced fluorescence intensity through an external magnet. The change of fluorescence intensity (△I) is positively related to the concentration of acetamiprid, which can be applied for the quantification of acetamiprid. Under optimal conditions, a linear detection range and detection limit are 0.89–114.18 μg/L and 0.65 μg/L, respectively. The probe was successfully used to detect acetamiprid in spiked paddy water, soil, pear, apple, wheat and cucumber. Average recoveries are 78.2%–103.5% with intra-day relative standard deviations (RSDs) of 2.6%–10.9% and inter-day RSDs of 4.3%–10.2%. The amounts of acetamiprid in the authentic paddy water and pear samples detected by the DNA probe are significantly correlated with that detected by high-performance liquid chromatography (HPLC).
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2018
·Vol. 28
·期 14
·1707152
·
IF 13.325
Zhi Li,Ganglin Wang,Yi Shen,Nannan Guo,Nan Ma
Circulating tumor cell (CTC) enumeration and analysis has emerged as an important platform for cancer diagnosis and prognosis. A great challenge, however, is to efficiently capture low abundant CTCs with high purity from blood samples in a rapid and high-throughput manner for accurate and sensitive CTC detection. Herein, a new class of DNA-templated magnetic nanoparticle-quantum dot (QD)-aptamer copolymers (MQAPs) is developed for rapid magnetic isolation of CTCs from human blood with high capture efficiency and purity approaching 80%. The phenotype of CTCs is simultaneously profiled with QD photoluminescence (PL) at single cell level. These MQAPs are constructed through hybridization chain reaction to achieve amplified magnetic response, extraordinary binding selectivity for target cells over background cells, and ultra bright ensemble QD PL for single cell detection. MQAPs are free from nonspecific binding that would otherwise compromise the capture purity of target cells. As a result, facile isolation and enumeration of rare CTCs in blood samples could be achieved in 20 min with high sensitivity and accuracy.
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高影响因子
危险品化学品经营许可证（带存储）