SENSORS AND ACTUATORS B-CHEMICAL
·
2026
·
IF 8.3
Xuemei Hu,Siying Che,Haiyan Fu,Yuanbin She
Colorimetric detection of trace Hg 2+ relies primarily on enzymes -catalyzed 3,3’,5,5’-tetramethylbenzidine (TMB) reactions, with two inherent drawbacks: substrate solubilization dependence on organic solvents and enzymes-associated limitations. By virtue of unique structural tunability and ionic properties, ionic liquids (ILs) dual-substitute enzymes and organic solvents, breaking through traditional bottlenecks via electrostatic assistance. Specifically, ILs enhance TMB water solubility efficiently through π-π interaction/charge-assisted hydrogen bond (CAHB) synergy, thus obviating organic solvents; meanwhile, CAHB and electrostatic interactions accelerate TMB-Hg 2+ redox reactions, eliminating exogenous H 2 O 2 and enzymes s and cutting response equilibrium time by ~35 min. Experiments confirmed that vs. CAHB-free blank systems shows a 2.2-fold increase in absorbance. Moreover, the system exhibits robust anti-interference, maintaining high sensitivity and stability across the pH range of 4.0–6.0. The paper-based ILs sensor allows naked-eye, on-site detection of trace Hg 2+ efficiently.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Yuting Sun,Hui Yang,Jiaqi Yuan,Limin Wang,Shanshan Song,Rongrong Chen,Xubin Bao,Li Jia,Tiantian Yang,Xiaofei Zhang,Qian He,Yong Gan,Zehong Miao,Jinxue He,Chunhao Yang
Poly(ADP-ribose) polymerase inhibitors (PARPi) have significant efficacy in treating BRCA-deficient cancers, although resistance development remains an unsolved challenge. Herein, a series of phthalazin-1(2H)-one derivatives with excellent enzymatic inhibitory activity were designed and synthesized, and the structure–activity relationship was explored. Compared with olaparib and talazoparib, compound YCH1899 exhibited distinct antiproliferation activity against olaparib- and talazoparib-resistant cells, with IC50 values of 0.89 and 1.13 nM, respectively. Studies of the cellular mechanism revealed that YCH1899 retained sensitivity in drug-resistant cells with BRCA1/2 restoration or 53BP1 loss. Furthermore, YCH1899 had acceptable pharmacokinetic properties in rats and showed prominent dose-dependent antitumor activity in olaparib- and talazoparib-resistant cell-derived xenograft models. Overall, this study suggests that YCH1899 is a new-generation antiresistant PARPi that could provide a valuable direction for addressing drug resistance to existing PARPi drugs.
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Journal of Proteomics
·
2023
·
IF 3.3
Bianxia Li,Zhuocheng Jin,Fan Yang,Huanan Li,Jiashu Liu,Zhengbing Jiang
The wide distribution of laccases in nature makes them involved in different biological processes . However, little information is known about how laccase participates in the defense machinery of bacteria against oxidative stress . The present study aimed to elucidate the oxidative stress response mechanism of Bacillus pumilus ZB1 and the functional role of bacterial laccase in stress defense. The oxidative stress caused by methyl methanesulfonate (MMS) significantly induced laccase activity and its transcript level. The morphological analysis revealed that the defense of B. pumilus ZB1 against oxidative stress was activated. Based on the proteomic study, 114 differentially expressed proteins (DEPs) were up-regulated and 79 DEPs were down-regulated. In COG analysis , 66.40% DEPs were classified into the category “Metabolism”. We confirmed that laccase was up-regulated in response to MMS stress and its functional annotation was related to “Secondary metabolites biosynthesis , transport and catabolism”. Based on protein-protein interaction prediction, two up-regulated DEPs (YcnJ and GabP) showed interaction with laccase and contributed to the formation of laccase stability and adaptability. The overexpressed laccase might improve the antioxidative property of B. pumilus ZB1. These findings provide an insight and the guidelines for better exploitation of bioremediation using bacterial laccase. Significance Bacillus pumilus is a gram-positive bacterium that has the potential for many applications, such as bioremediation. The expression of bacterial laccase is significantly influenced by oxidative stress, while the underlying mechanism of laccase overexpression in bacteria has not been fully studied. Elucidation of the biological process may benefit the bioremediation using bacteria in the future. In this study, the differentially expressed proteins were analyzed using a TMT-labeling proteomic approach when B. pumilus was treated with methyl methanesulfonate (MMS). Reactive oxygen species induced by MMS activated the secondary metabolites biosynthesis, transport, and catabolism in B. pumilus , including laccase overexpression. Moreover, the simultaneously up-regulated YcnJ and GabP may benefit the synthesis and the stability of laccase, then improve the antioxidative property of B. pumilus against environmental stress. Our findings advance the understanding of the adaptive mechanism of B. pumilus to environmental conditions.
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JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2023
·Vol. 170
·期 11
·117513
·
IF 3.9
Qing-Zheng Zhang,Chun-Bo Su,San-Jun Shi,Yue Gao,Rong-Fu Huang
Because the cytotoxic DNA methylated bases are chemically inert and small in size, limited biosensing strategies especially with high sensitivity were established to detect DNA methylation damage. In this work, a label-free electrochemical assay was proposed for the sensitive detection of DNA methylation damage in dsDNA film on indium tin oxide electrode. The human alkyladenine DNA glycosylase was employed to recognize and selectively remove DNA methylated bases, generating apurinic site. Subsequently, exonuclease III not only further converted the methylation sites into strand breaks, but also progressively removed nucleotides from the 3' to 5' end starting from the apurinic sites. These processes could maximum amplify DNA methylation damage, also confirmed by gel electrophoresis and fluorescence measurements. The damaged DNA film bound much less electrochemical indicator, Ru(bpy)2(dppz)2+, and accompanied by an anodic current drop. As a result, DNA methylation damage produced with as low as 10 μM of methyl methanesulfonate can be detected, which was 100-fold lower than the previously reported photoelectrochemical sensing strategy. Other DNA base modification products showed much less decrease of oxidation current, demonstrating its good selectivity. This strategy can be utilized to sensitively and rapidly assess the genotoxicity of environmental pollutants.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
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IF 6.291
Jiashu Liu,Jianhui Chen,Kangjia Zuo,Huanan Li,Fang Peng,Qiuping Ran,Rui Wang,Zhengbing Jiang,Huiting Song
To alleviate the risk of textile effluent, the development of highly effective bioremediation strategies for synthetic dye removal is needed. Herein, we aimed to assess whether intensified bioactivity of Bacillus pumilus ZB1 by oxidative stress could improve the removal of textile dyes. Methyl methanesulfonate (MMS) induced oxidative stress significantly promoted laccase expression of B. pumilus ZB1. Both the level of hydrogen dioxide and superoxide anion showed a significant positive correlation with laccase activity (RSQ = 0.963 and 0.916, respectively) along with the change of MMS concentration. The regulation of laccase expression was closely related to oxidative stress. The overexpressed laccase in the supernatant improved the decolorization of synthetic dyes (16.43% for Congo Red, 54.05% for Crystal Violet, and 41.61% for Reactive Blue 4). Laccase was subsequently expressed in E. coli . Investigation of the potential of bacterial laccase in dye remediation using Congo Red showed that an effective degradation of azo dye could be achieved with laccase treatment. Laccase remediation alleviated the cytotoxicity of Congo Red to human hepatocytes. In silico study identified eight amino acid residues of laccase involved in binding with Congo Red. Overall, regulation of oxidative stress towards bacterium can be used as a promising approach for the improvement of bacterial bioactivity in synthetic dye remediation.
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Environmental Science-Nano
·
2021
·Vol. 8
·期 9
·2660-2675
·
IF 8.131
Qingying Shi,Jingchun Tang,Xiaomei Liu,Rutao Liu
The widespread presence of nanoplastics (NPs), with small particle sizes and high specific surface area, leads to the exposure and potential health risk for humans. The plastic particles widely detected in the indoor and outdoor air imply potential threats to the human respiratory system. However, the impact of aging NPs on their toxicity has been poorly considered, although it is an inevitable process suffered by them once they enter the environment. In this study, the aging of polystyrene (PS) NPs by photodegradation under ultraviolet irradiation for 2 months was investigated, and the toxicities of pristine and aged NPs to human lung epithelial A549 cells were compared. The results revealed alterations in the physicochemical properties with the size of NPs reduced and the abundant oxygen-containing groups formed on the surface. The toxic effects of the pristine and aged NPs at the cellular level on the cell viability, oxidative stress, membrane damage and mitochondrial dysfunction were illustrated in A549 cells, indicating that the aged NPs exhibited greater cytotoxicity than pristine NPs and this toxicity was in a positively aging time-related manner. Transcriptome analysis further revealed the impacts of aged NPs on A549 cells at the molecular level, wherein the aged NPs presented aggravated interference in gene expression, reconfirming the elevated toxicity of NPs after ultraviolet-induced photodegradation. This study highlights the importance of photodegradation on the toxicity of NPs in human health, which is of great significance for the risk assessment of NPs.
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ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Ying Li,Xiwen Zhang,Yiyu Wang,Xue Mu,Yuanbo Tu,Peng Sun,Yaolong Wang,Gongjun Yang,Lifeng Kang,Chunyong Wu,Junying Zhang
The insertion of a single nanoelectrode into the cell or fluorescence detection has enabled the nondestructive tracking of intracellular biomarkers. However, the reliance on extremely expensive micromanipulators or intricate fluorescent probes has limited their widespread application. To address this challenge, we propose a novel strategy that employs modified multiwalled carbon nanotubes (MWCNTs) as artificial transmembrane electron tunnels. These MWCNTs can be spontaneously and nondestructively semiembedded within cells while exhibiting remarkable conductivity. When the photosensitive electrodes on the cell surface are illuminated, photogenerated electron–hole pairs are produced. The holes can enter the cell through the nanowires, thus promoting oxidation reactions with target molecules and generating real-time electrical signals for monitoring intracellular biomarkers. Meanwhile, the engineered recognition element on the nanowire transitions to an excited state and subsequently returns to the ground state through electrochemiluminescence (ECL), enabling in situ visualization of intracellular biomarkers. This groundbreaking approach not only eliminates the need for micromanipulators and fluorescent probes but also enables simultaneous electrical and optical monitoring of intracellular biomarker levels, significantly reducing false-positive risks. This innovation was validated to be feasible using NADH as an intracellular target molecule, marking a shift in intracellular sensing strategies.
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Journal of Genetic Engineering and Biotechnology
·
2025
·
IF 2.8
Zhongyi Cong,Jingyuan Jiang,Mengyuan Li,Chenqi Yan,Jiayin Li,Xinmin Zhang
Background Double-strand breaks (DSBs) are repaired through the coordinated action of DNA damage checkpoint pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) mechanisms. Given the complexity of DSB repair networks, the identification of novel regulatory factors remains essential for a comprehensive understanding of genomic stability maintenance. Fmp45, a membrane protein previously implicated in salt stress response but with no known role in DNA repair, was found to be upregulated in multiple DNA damage-related transcriptomic datasets (GEO: GSE83454, GSE155701, GSE74642). This observation led us to hypothesize that Fmp45 might represent a previously unrecognized component of the DSB repair machinery. In this study, we demonstrate that Fmp45 functions as a zeocin-specific modulator of the DSB response in Saccharomyces cerevisiae. Methods Growth phenotypes were analysed to investigate FMP45 deletion ( fmp 45Δ) and its genetic interactions with other genes, protein expression and Rad53 phosphorylation was assessed by Western blotting, protein localization was analysed by Laser confocal microscopy, cell cycle progression was determined by flow cytometry, and protein–protein interactions was probed yeast two-hybrid assays. Results Growth assays revealed that fmp 45Δ mutants exhibited hypersensitivity to DSBs induced by zeocin but not to other DNA lesions caused by hydroxyurea, methyl methanesulfonate, 4-nitroquinoline-1-oxide, or camptothecin. Genetic interaction analysis showed that Fmp45 cooperated with checkpoint gene Rad9 but not with HR-related genes ( Sae2 , Exo1 ) or NHEJ factor yku70 . Laser confocal microscopy confirmed that FMP45 deletion did not impair nuclear localization of Rad51, a key mediator of HR-mediated DNA strand invasion. Further analysis of Rad53 phosphorylation/dephosphorylation dynamics, growth phenotypes of fmp 45Δ with phosphatase ( ptc 2Δ, pph 3Δ) and checkpoint effector ( rad 9Δ, mrc 1Δ) mutants, cell cycle profiling, and yeast two-hybrid assays demonstrated that Fmp45 interacts with Ptc2 to promote Rad53 dephosphorylation, thereby preventing excessive cell cycle arrest. Conclusion These findings elucidate a critical checkpoint-phosphatase coordination mechanism ensuring timely DNA damage recovery and genomic stability, identifying Fmp45 as a key regulator balancing DNA repair fidelity with cell cycle resumption following DSBs.
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