Research
·
2026
·
IF 12.9
Ting Xu,Xiaoting Yan,Tingting Wang,Liping Cui,Shangshang Qin,Ruige Yang,Hong Yao,Yong Guo
The rise of multidrug-resistant bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), poses a serious threat to human health, necessitating an urgent need to develop innovative antibacterials with multifunctions for this. Here, focusing on integrating multi-antimicrobial mechanisms with visual monitoring, we report a novel phenanthro[9,10-d]imidazole fluorogen 9b, outstanding for its antibacterial effects against S. aureus and various clinical MRSA isolates (minimum inhibitory concentration = 0.5 to 1 μg/ml) with rapid bactericidal activity, high membrane selectivity, and low susceptibility to drug resistance. Further investigation revealed its dual antimicrobial mechanisms of action by concurrently disrupting bacterial cell membranes and inducing bacterial DNA degradation to accelerate bacterial death. Ultraviolet–visible and fluorescence spectroscopy studies showed that the fluorescence intensity of 9b was dramatically enhanced when it interacted with S. aureus. Notably, in vivo studies demonstrated that 9b effectively treated both skin and thigh MRSA infections, showing a favorable safety profile and superior efficacy compared to the first-line antibiotic vancomycin. The “dual-mechanism” fluorescent phenanthro[9,10-d]imidazole fluorogen 9b holds promise as a candidate for developing innovative antibacterial agents that enable simultaneous real-time diagnosis and treatment.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
·
2026
·Vol. 62
·期 7
·153
·
IF 0.8
Gao En,Zhang Wanli,Zhang Haoying,Guo Yajie,Ma Jinting,Wang Zixin,Shi Ningning,Shangguan Lida,Li Shouhu
In the search for novel anticancer agents, a series of triazole–urea hybrids were designed and synthesized. Among them, compound 5a exhibited potent and selective cytotoxicity against hepatocellular carcinoma (HCC) cells, displaying an IC 50 value of 8.32 ± 1.26 μM against the Huh-7 cell line, while exerting minimal effects on other cancer cell lines and normal hepatocytes (LO2). Mechanistic investigations revealed that 5a triggers DNA damage and activates autophagy, which collectively contribute to the suppression of cell proliferation and the induction of dose-dependent apoptosis. Taken together, 5a represents a promising lead compound for the development of novel anti-HCC therapeutics, warranting further in-depth evaluation.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2026
·
IF 8.3
Junhua Chen,Zihao Zhang,Chengshuai Liu
Visual and on-site monitoring of aflatoxin B1 (AFB1) with high sensitivity and selectivity is essential for ensuring food safety. We herein developed a colorimetric biosensor for AFB1 monitoring based on target-mediated DNA self-replicating circuits. The aptamer-AFB1 recognition liberated the trigger DNA (T), which initiates DNA assemblies involving hairpin probes H1, H2 and H3. Through a series of DNA toehold hybridizations and strand displacements, a ternary hybrid H1-H2-H3 will be produced. At one arm of the H1-H2-H3 hybrid is a newly regenerated T and at other two arms are the Mg 2 + -DNAzymes. The Mg 2+ -DNAzyme can cleave the substrate chain to liberate another blocked T sequence and a G-quadruplex sequence. All three types of T probes can be recycled to form the DNA self-replicating circuits than can continuously generate H1-H2-H3 products. The G-quadruplex DNAzyme catalyzes the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to produce a colorimetric signal that is observable directly by the naked eye. This enzyme-free DNA circuit-based biosensor exhibits high sensitivity, with a visual detection limit reaching 0.1 pM. This biosensor is robust and can be employed to detect AFB1 in corn, peanut, and rice samples with good reliability. Using AFB1, deoxynivalenol (DON), and fumonisin B1 (FB1) as three logic inputs, we further built cascaded INHIBIT-AND and AND-OR logic gates, which possess great potential for intelligent sensing of various mycotoxins.
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ELECTROCHIMICA ACTA
·
2011
·
IF 3.65
Qingxiang Wang,Feng Gao,Xuan Zhang,Bin Zhang,Shunxing Li,Zhengshui Hu,Fei Gao
A composite film that contained CeO 2 –ZrO 2 hollow nanospheres and chitosan was deposited on a gold electrode using a one-step electrodeposition based on the pH-dependent solubility of chitosan. Electrochemical characterization experiments showed that the electroactive surface of the modified electrode was significantly enhanced by the introduction of the CeO 2 –ZrO 2 nanospheres into the chitosan gel during electrodeposition . Furthermore, an electrochemical DNA biosensor was fabricated based on the synergistic affinity of CeO 2 –ZrO 2 and chitosan in the nanocomposite film to probe DNA . DNA hybridization assays suggested that the target DNA could be quantified over a wide dynamic range of 1.63 × 10 −13 M–1.63 × 10 −8 M with a detection limit of 1.0 × 10 −13 M using methylene blue as an electrochemical indicator. This work describes a simple strategy for the preparation of a stable and conductive interface for electrochemical detection of DNA hybridization and opens a path for the application of CeO 2 –ZrO 2 nanospheres and chitosan in DNA electrochemical biosensing analysis.
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JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2026
·Vol. 40
·期 1
·e70672
·
IF 2.8
Junqi Xiao,Yang Xie,Leiying Zhang,Rong Ye,Xiangtai Zeng
Atherosclerosis (AS), driven by endothelial dysfunction, is exacerbated by environmental cadmium (Cd 2+ ). This study elucidates the molecular mechanism by which Cd 2+ promotes AS, focusing on the role of growth arrest and DNA damage-inducible 45 gamma (GADD45G). Clinical correlation between plaque Cd 2+ levels and plaque burden was assessed in human samples. In vivo studies utilized apolipoprotein E-deficient (ApoE −⁄− ) mice fed a high-fat diet (HFD) with varying cadmium chloride (CdCl 2 ) doses. In vitro analyses employed human umbilical vein endothelial cells (HUVECs) treated with CdCl 2 , combined with siRNA knockdown, MEKK4 overexpression plasmids, and pharmacological agonists. GADD45G −/− zebrafish were generated and exposed to HFD and CdCl 2 . Functional assays included cell viability, apoptosis, migration, tube formation, inflammation, lipid deposition (Oil Red O), and molecular analyses. Cd 2+ concentration positively correlated with plaque area in humans and dose-dependently increased plaque burden in ApoE −⁄− mice. CdCl 2 upregulated GADD45G expression and activated the MEKK4–p38MAPK pathway in HUVECs. GADD45G knockdown attenuated CdCl 2 -induced endothelial apoptosis, impaired migration and angiogenesis, and reduced inflammation and MAPK pathway activation. These protective effects were reversed by the p38MAPK agonist anisomycin or by MEKK4 overexpression. In zebrafish, CdCl 2 exacerbated HFD-induced vascular lipid deposition and inflammatory gene expression. GADD45G knockout mitigated these effects induced by HFD, which were reversed by CdCl 2 co-exposure. Cd 2+ exacerbates AS by inducing endothelial dysfunction via GADD45G-mediated activation of the MEKK4–p38MAPK signaling axis. Thus, the GADD45G–MEKK4–p38MAPK axis represents a novel therapeutic target for mitigating Cd 2+ -associated cardiovascular risk.
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Shilan Fu,Ying Peng,Yuting Yang,Ruyi Xu,FengFu Fu,Weijuan Yang
An improved multi-target SELEX yielded an aptamer with binding affinity for 5 NNIs. • Joint characterization clarified enthalpy-driven induced-fit recognition mechanism. • Unlabeled colorimetric sensor realized single/total fast screening of 5 NNIs in food. Neonicotinoid insecticides (NNIs) are a class of fourth-generation insecticides widely used in agriculture. It is crucial to discover bioreceptors with specific binding affinity toward multiple or even all commonly-used NNI compounds, and further develop high-throughput methods for rapid screening/determination of multiple or even all commonly-used NNI compounds in foods. Herein, an improved combined SELEX strategy integrating gradient multi-target parallel selection and serial counter-selection was developed for screening cross-reactive aptamers toward NNIs. One of the obtained cross-reactive aptamers, NNI-03, can recognize five commonly-used NNI compounds, including imidacloprid (IMI), thiacloprid (TCP), imidaclothiz (IMZ), thiamethoxam (TMX) and acetamiprid (ACE), with excellent specificity and binding affinities ( K d values) within comparable orders of magnitude (low-micromolar range). The practicality and reliability of NNI-03 were validated by developing a label-free colorimetric aptasensor for rapid screening/determination of above five NNI compounds, either individually or collectively, with a limit of detection (LOD) of 0.05–0.10 μM, a limit of quantitation (LOQ) of 0.25–0.50 μM and no interference from non‑neonicotinoid pesticides. The LOD and LOQ are all lower than the maximum residue limits (MRL) of these five NNIs in most foods as specified by Chinese national standards (GB-2763-2026). The aptasensor was successfully applied to detect these five NNI compounds, either individually or collectively, in tomato and fresh milk samples. This work not only offers a promising bioreceptor for the construction of diverse high-throughput methods but also directly provides a simple and cost-effective analytical approach, enabling rapid screening/monitoring of individual or co-existing residues of above five NNI compounds in foods. Download: Download high-res image (172KB) Download: Download full-size image
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JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Xiao-Meng Liu,Zhe Li,Xin-Ru Xie,Jia-Qian Wang,Xin Qiao,Xin Qiao,Cheng-Zhi Xie,Jing-Yuan Xu
Exploring multi-targeting chemotherapeutants with advantages over single-targeting agents and drug combinations is of great significance in drug discovery. Herein, we employed phytogenic evodiamine (EVO) and conventional Pt(II) drugs to design and synthesize multi-target EVO–Pt(IV) anticancer prodrugs (4–14). Among them, compound 10 exhibited a 118-fold enhancement in the IC50 value compared to cisplatin and low toxicity to normal cells. Further studies proved that 10 significantly enhanced intracellular Pt accumulation and DNA damage, perturbed mitochondrial membrane potential, inhibited cell migration and invasion, upregulated reactive oxygen species levels, and induced apoptosis and autophagic cell death. Molecular docking assay revealed that 10 fits perfectly into the extracellular signal-regulated protein kinase (ERK)-1 pocket, which was verified to produce profound ERK suppression. Most strikingly, compound 10 exhibited superior in vivo antitumor efficiency and effectively attenuated systemic toxicity. Our results emphasize that functionalizing platinum drugs with the multi-target EVO could generate synergistically excellent anticancer activity with low toxicity and decreased resistance, which may represent a brand-new cancer therapy modality.
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TALANTA
·
2023
·
IF 6.1
Guo Ge,Tianlin Wang,Zihou Liu,Xiaomeng Liu,Tiange Li,Yuntang Chen,Jialin Fan,Erkigul Bukye,Xianqing Huang,Lianjun Song
Realizing the simultaneous speedy detection of multiple mycotoxins in contaminated food and feed is of great practical importance in the domain of food manufacturing and security. Herein, a fluorescent aptamer sensor based on self-assembled DNA double-crossover was developed and used for effective simultaneous quantitative detection of aflatoxins M 1 and B 1 by fluorescence resonance energy transfer (FRET). Fluorescent dye-modified aflatoxin M 1 and B 1 aptamers are selected as recognition elements and signal probes, and DNA double crosses are consistently locked by the aflatoxin aptamers, which results in a “turn-off” of the fluorescent signal. In the presence of AFM 1 and AFB 1 , the aptamer sequences are more inclined to form Apt-AFM 1 and Apt-AFB 1 complexes, and the fluorescent probes are released from the DNA double-crossing platform, leading to an enhanced fluorescent signal (Cy3: 568 nm; Cy5: 660 nm). Under the optimal conditions, the signal response of the constructed fluorescent aptamer sensor showed good linearity with the logarithm of AFM 1 and AFB 1 concentrations, with detection limits of 6.24 pg/mL and 9.0 pg/mL, and a wide linear range of 0.01–200 ng/mL and 0.01–150 ng/mL, respectively. In addition, the effect of potential interfering substances in real samples was analyzed, and the aptasensor presented a good interference immunity. Moreover, by modifying and designing aptamer probes, the sensor can be applied to high-throughput simultaneous screening of other analytes , providing a new approach for the development of fluorescent aptamer sensors.
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BIOSENSORS & BIOELECTRONICS
·
2022
·
IF 12.545
Xiaohai Yan,Gengan Du,Hong Chen,Qiannan Zhao,Qi Guo,Jianlong Wang,Zhouli Wang,Wei Song,Qinglin Sheng,Yane Luo,Yahong Yuan,Tianli Yue
Patulin (PAT) is an unsaturated lactone mycotoxin primarily produced by Penicillium expansum and Aspergillus clavatus . Given the potential health risks and economic losses associated with PAT, the rapid detection of PAT using fluorescent aptasensors is of significant importance in evaluating food safety. However, it easily increases the cost and complexity caused by signal labeling. We combined TCPP/BDC-NH 2 mixed ligands functionalized Zr metal–organic frameworks (Zr-MOF mix ) and terminated three-stranded DNA gates (ttsDNA gates) to fabricate a label-free fluorescent aptasensor for PAT detection. The Zr-MOF mix system was synthesized via a one-pot strategy and could be used to address the problem of pore size limitation and increase the loading amounts of dyes. TtsDNA gate was integrated into the Zr-MOF mix system to control the release of dyes, exhibiting a high signal-to-background ratio. The single-stranded aptamer region in ttsDNA gate situated away from the surface of the Zr-MOF mix , resulting in a natural release of dyes in the absence of PAT. While binding to PAT resulted in target-induced conformational changes that helped form the hairpin structure of the aptamer. This structure hindered the release of dyes from the pores of Zr-MOF mix , thus reducing the fluorescence signals intensity. The stimuli-responsive DNA-gated material provides a platform for PAT analysis under conditions of a low limit of detection (0.871 pg/mL). Furthermore, the excellent specificity and anti-interference of the fluorescent aptasensor make the system suitable for the analysis of apple juice samples. This label-free strategy is cheaper and simper compared with labeled detection, especially for the development of multi-target-detection.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2022
·
IF 9.221
Li Shuofeng,Wang Fangfang,Chun Wang,Zhi Wang,Qiuhua Wu
As vital biomarkers for diagnosis of diseases, the anomalously expressed microRNAs (miRNAs) are closely linked to the occurrence and development of many diseases. Quantitative analysis of miRNAs has remarkable significance to clinical diagnosis and therapy of different cancers. In this study, the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) 13a (CRISPR/Cas13a) system was first exploited to directly and specifically recognize the miRNA at the guidance of CRISPR RNA (crRNA), which can activate the nonspecific trans-ribonuclease activity of Cas13a. Then, combining the CRISPR-Cas13a system with terminal deoxynucleotidyl transferase (TdT)-triggered template-free DNA extension to form the fluorescent copper nanoparticles (CuNCs), a simple but sensitive method (named as Cas13a-TFCN) was developed for highly specific detection of miRNA. Based on the CRISPR/Cas13a system coupled with TdT-triggered simple but efficient signal amplification strategy, the developed Cas13a-TFCN method showed high sensitivity for miRNA detection with the low detection limit of 0.7 fM. Furthermore, the proposed Cas13a-TFCN approach was successfully applied for accurate quantification of miRNA in complex biological samples, indicating its practical application ability. Moreover, featuring high sensitivity and simplicity without complicated probe design and fluorophore labeling, the proposed Cas13a-TFCN has a promising applications prospect in clinical diagnosis.
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Journal of Pharmaceutical Analysis
·
2022
·
IF 14.026
Liu Liu,Juncheng Hong,Wenhai Wang,Shu Xiao,Hongzhen Xie,Qiqin Wang,Ning Gan
In this study, a fluorescent (FL) aptasensor was developed for on-site detection of live Salmonella typhimurium (S.T.) and Vibrio parahaemolyticus (V.P.). Complementary DNA (cDNA) of aptamer (Apt)-functionalized multicolor polyhedral oligomeric silsesquioxane-perovskite quantum dots (cDNA-POSS-PQDs) were used as encoded probes and combined with dual-stirring-bar-assisted signal amplification for pathogen quantification. In this system, bar 1 was labeled with the S.T. and V.P. Apts, and then bar 2 was functionalized with cDNA-POSS-PQDs. When S.T. and V.P. were introduced, pathogen-Apt complexes would form and be released into the supernatant from bar 1. Under agitation, the two complexes reached bar 2 and subsequently reacted with cDNA-POSS-PQDs, which were immobilized on MXene. Then, the encoded probes would be detached from bar 2 to generate FL signals in the supernatant. Notably, the pathogens can resume their free state and initiate next cycle. They swim between the two bars, and the FL signals can be gradually enhanced to maximum after several cycles. The FL signals from released encoded probes can be used to detect the analytes. In particular, live pathogens can be distinguished from dead ones by using an assay. The detection limits and linear range for S.T. and V.P. were 30 and 10 CFU/mL and 10 2 –10 6 CFU/mL, respectively. Therefore, this assay has broad application potential for simultaneous on-site detection of various live pathogenic bacteria in water.
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Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 32
·6107-6117
·
IF 7.571
Siying Xie,Cheng Qin,Furong Zhao,Zhaoyang Shang,Pei Wang,Muhammad Sohail,Xing Zhang,Bingzhi Li
CRISPR-driven biosensing is developing rapidly, but current studies mostly adopt dye-labeled ssDNA as the signal reporter, which is costly and unstable. Herein, we developed a label-free and low-background reporter for CRISPR/Cas12a signaling by integrating DNA-templated copper nanoclusters (DNA–CuNCs) and exonuclease I (EXO I). The template of the DNA–CuNCs was rationally designed as a ds-/ss-DNA hybrid, ensuring that after a quick and nonpersistent cut of Cas12a, a majority of the template can be digested by EXO I. Based on this novel reporter, a biosensor termed CRISPR-CNS (cost-effective, nimble, and sensitive copper nanocluster sensor integrating CRISPR) was developed. Due to the high signal-to-background ratio of our proposed reporter, CRISPR-CNS shows excellent performances for nucleic acid detection, yielding a detection limit of 20 copies for SARS-CoV-2 RNA. Considering its facile synthesis, robust fluorescence, effective cost, and good sensitivity, this combination shall serve as a highly potential output for CRISPR-based point-of-care testing.
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