MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 10
·1-10
·
IF 5.833
Zheng Delun,Chen Min,Peng Jingjun,Chen Jiayang,Chen Tufeng,Chen Yaowen,Huang Linjia,Gao Wenhua
HKUST-1 MOFs and its derivative HKUST-CuO were coupled with TiO 2 nanoparticles to form the heterogeneous composites of HKUST-1/TiO 2 and HKUST-CuO/TiO 2 based on their well-suitable bandgap energies (Eg). Compared with mono-component HKUST-1 or HKUST-CuO, the prepared composites displayed photoelectrochemical (PEC) response due to the synergistic effect from their heterogeneous structure. Higher photocurrent response was obtained on HKUST-CuO/TiO 2 -modified ITO electrode (HKUST-CuO/TiO 2 /ITO), which could be attributed to the hollow structure with a thin shell of HKUST-CuO greatly enhancing visible spectra harvesting. The CuO component in HKUST-CuO not only could accelerate electron transfer on the heterojunction interface but also effectively separate the photo-generated charge carriers (e −1 /h + ). Based on the excellent PEC performance of prepared photoactive composite material, under visible-light excitation ( λ ≥ 420 nm) and with a working potential of 0 V (vs. Ag/AgCl), the S1 (probe DNA)/HKUST-CuO/TiO 2 /ITO PEC platform was successfully fabricated for colitoxin DNA detection without using ascorbic acid (AA) as an electron donor. Compared with the analysis results on S1/HKUST-1/TiO 2 /ITO electrode, S1/HKUST-CuO/TiO 2 /ITO displayed a wider linear response range from 1.0 × 10 −6 to 4.0 × 10 −1 nM with a lower detection limit of 3.73 × 10 −7 nM (S/ N = 3), the linear regression equation was Δ I (10 −6 A) =0.5549–0.1858 log ( C S2 /M), which confirmed the HKUST-CuO could improve sensitivity because of its prominent PEC property. The relative standard deviation (RSD) of the PEC sensor for target DNA detection of 2.0 × 10 −4 nM was 7.4%. The proposed DNA biosensor also possessed good specificity and stability. Hence, this reported work was a promising strategy for molecular diagnosis in the bio-analysis field. Graphical abstract
(A) Schematic illustration of the preparation process of the proposed PEC biosensors for colitoxin DNA detection. (B) The preparation process of HKUST-1 and HKUST-CuO.
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Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-16
·
IF 6.1
Xiong Yi,Chen Jiawen,Liang Wei,Li Kun,Huang Yingqi,Song Jingwen,Zhang Baoyu,Qiu Xiusheng,Qiu Dongbo,Zhang Qi,Qin Yunfei
Background Liver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated. Methods Mouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models. Results Our research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization. Conclusions The results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury.
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COPD-Journal of Chronic Obstructive Pulmonary Disease
·
2023
·
IF 2.2
Chuanxin Yang,Libing Deng,Fang Bao,Hui Jiang,Long Zhang
Chronic obstructive pulmonary disease (COPD) is a difficult-to-cure disease that mainly affects the respiratory system. Inhaled anesthetic drug such as sevoflurane plays a controversial role in COPD by different concentration, but the underlying epigenetic mechanism remains unclear. Here, we prepared lipopolysaccharide (LPS)-induced COPD rat model, and isolated Alveolar type II (ATII) cells. We mainly focused DNA methylation on the promoter of COPD-related genes including Sftpa1, Napsa, Ca2, Sfta2, Lamp3, Wif1, Pgc, and Etv5. We observed COPD rat treated by sevoflurane with low (0.5%) and high (2%) concentrations displayed an opposite DNA methylation pattern. These six genes' promoter were all hypomethylated by 0.5% sevoflurane whereas hypermethylated by 2% sevoflurane, accompanied with the opposite transcriptional activity. We further verified that the DNMT1 binding ability contributed to DNA methylation these six genes' promoter. Moreover, we also captured DNMT1 and identified REC8 meiotic recombination protein (REC8) as the specific binding protein only existed in ATII cells treated with 0.5% sevoflurane rather than 2% and control. The binding ability of REC8 on these target genes' promoter showed highly positive correlation with DNMT1. In summary, we uncovered a potential epigenetic role of sevoflurane with low concentration in ATII cells of COPD that may help us deeply understand the pathogenesis and treatment mechanism of inhaled anesthesia drugs in COPD via a dose-dependent manner.
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ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Jinai Chen,Yujiao Wei,Liming Wang,Leyi Chen,Shengnan He,Honglin Liu
We present a digital surface-enhanced Raman spectroscopy (SERS) platform enabling enzyme- and amplification-free single-molecule DNA detection through Poisson distribution-driven quantification and geometrically optimized plasmonic nanostructures. Utilizing high-throughput UV lithography, we fabricated large-area nanopillar arrays (1.5 × 1.5 cm) with tunable heights (500–1300 nm) and periodicities (4–10 μm), addressing key limitations in conventional SERS methods via three innovations: (1) dynamic hotspot generation: Target DNA induces plasmonic dimerization between functionalized gold nanoprobes and Au-capped nanopillars, creating spatially resolved SERS enhancement (1326 cm–1 DTNB signal), (2) digital counting algorithms: Compensate Raman intensity variations by quantifying activated pillars as discrete molecular events, and (3) geometric confinement: Spatial confinement effects enabling statistically robust single-molecule occupancy. This platform achieved 10 fM sensitivity for Diaporthe spp. DNA detection, outperforming PCR-electrophoresis (1 pM) by 2 orders of magnitude. Applied to presymptomatic kiwifruit diagnosis, the system identified pathogen DNA in asymptomatic samples prior to visual symptom development, validated by characteristic DTNB peaks (1326 cm–1) absent in negative controls. The modular design permits multiplexed detection through probe diversification, while the absence of enzymatic steps enables field-deployable operation. By integrating single-molecule statistics with plasmonic signal amplification, this work establishes a robust framework for precision molecular diagnostics, demonstrating transformative potential for agricultural pathogen surveillance and low-abundance biomarker analysis. The technology’s batch-producible nanopillar architecture and digital quantification strategy overcome longstanding reproducibility challenges in SERS-based detection, positioning it as a versatile tool for next-generation biosensing applications.
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WATER RESEARCH
·
2025
·
IF 12.4
Shuangshuang Cheng,Rui Cui,Yuehong Sun,Yuxin Li,Yangjian Zhou,Zilong Song,Xin Yang
The degradation kinetics and mechanism of four free bases were comparatively investigated during UV/H 2 O 2 and UV/PDS water treatment processes. The UV/PDS system demonstrated superior removal efficiency for all four bases compared to the UV/H 2 O 2 process. Pyrimidine bases (cytosine and thymine) exhibited notably faster degradation rates than purine bases (adenine and guanine) in both advanced oxidation systems. Guanine (G) was then selected as a representative free base to investigate the internal and external reverse-reduction process. The time-resolved transient spectra shows that key intermediate product G(-H) • was formed in both processes, where this radical play critical role in initiating reverse-reduction process. During UV/H 2 O 2 process, the G’s antioxidant intermediates (e.g. 8-oxoG) trigger an internal reverse-reduction process, which can reduce G(-H) • back to their parent compounds. The second-order rate constant for the reaction between of G(-H) • and 8-oxoG was quantitatively determined to be (2.60 ± 0.12) × 10 8 M −1 s −1 . Conversely, during the UV/PDS process, the reverse-reduction process of G(-H) • is predominantly governed by external inhibition mediated by dissolved organic matter (DOM), with no competing internal pathway observed. Specifically, intrinsic intermediate products generated during UV/H 2 O 2 treatment initiate an internal reverse-reduction process, effectively suppressing DOM-driven external reduction. This may also explain why the degradation rates of free bases were lower in the UV/H₂O₂ system than in the UV/PDS system, and why DOM exhibited a stronger inhibitory effect on their degradation in the UV/PDS process compared to UV/H₂O₂. DFT calculations were conducted to verify the proposed mechanisms, which were applicable to the four studied bases. Studying both internal and external reverse-reduction processes can significantly enhance the understanding of compounds transformation pathways and enhance the accuracy of predicting degradation rates in real-world aqueous systems.
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BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Linlin Han,Hongyan Tan,Jungjoon Lee,Peng Wang,Yuqing Zhao
Based on the significant biological activities and the remarkable physical and chemical properties of 1 H -1,2,3-triazole pharmacophore, we herein adopted the strategy of click chemistry to combine the triazole fragment and the unique scaffold of 25-OCH 3 -PPD ( AD-1 ) to design a series of potent compounds inducing apoptosis and DNA damage. The anti-proliferative effect was verified by MTT assay and colony formation assay. DNA double-stand breaks (DSBs) were obtained by observing the nuclear focus formation and the protein expression of γ-H2AX. Cell cycle arrest was evaluated by the cycle-related proteins such as CDK2, CDK4, CDK6, Cyclin D1 and P 21. Apoptosis was assessed by flow cytometry, mitochondrial membrane potential (MMP) detection and the expression of apoptosis-related proteins. Reactive oxygen species (ROS) generation was measured with 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) staining. According to SAR analysis, the most potent compound 6a exhibited great inhibitory effect against A549 cells, which IC 50 value of 2.84 ± 0.68 μM. Furthermore, 6a remarkably induced DNA damage, cell cycle arrest and apoptosis in A549 cells. 6a treatment increased the levels of ROS. Network pharmacology and molecular docking predicted the potential signaling pathways and ligand-receptor interactions, and the results of western blotting showed that 6a inhibited the PI3K/Akt/Bcl-2 signaling pathway by decreasing PI3K and Bcl-2 and total level of Akt expression, while Bax and Cyt c were increasing in 6a -treated A549 cells. As mentioned above, 6a has a potent inhibitory effect in A549 cells through induction of DNA damage, apoptosis via ROS generation and modulation of PI3K/Akt/Bcl-2 signaling pathway.
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AQUATIC TOXICOLOGY
·
2025
·
IF 4.3
Yun-xia Hou,Xiang-sheng Hong,Shi-yin Tang,Wang Liu,Zhi-tong Li,Juan Wang,Sai-hong Yan,Jian-hui Qin,Jin-miao Zha
The accumulation of ibuprofen (IBU) in freshwater sediments poses significant risks to benthic bivalves, yet its chronic ecological impacts remain insufficiently studied. Here, Asian clams ( Corbicula fluminea ) were exposed to 20, 200, and 2000 µg/L IBU for 28 days. The viscera were identified as the primary target organ for IBU toxicity, with bioconcentration factors (BCFs) ranging from 3.03–6.05 across treatments and a 1.3- to 3.3-fold increase in in digestive gland vacuolation damage. Chronic IBU exposure also induced neurotoxicity, evidenced by acetylcholinesterase inhibition, and potentially associated behavioral disturbances. Filtration and burrowing rates decreased significantly at 200 and 2000 µg/L, while escape rates increased, reflecting a trade-off between avoidance and burrowing under stress. At 20 µg/L, escape fluctuations were most pronounced, suggesting sub-threshold behavioral modulation. The trade-off between escape and burrowing highlights the adaptive yet costly responses of bivalves to pharmaceutical stress. Transcriptomic profiling demonstrated marked enrichment of apoptotic and pro-inflammatory pathways. Notably, while antioxidant defenses remained unaltered in clams, IBU exposure consistently upregulated COX-2 activity, with concomitant induction of genotoxic effects evidenced by DNA strand breakage and activation of caspase-9 mediated intrinsic apoptotic pathways. This work provides critical insights for managing pharmaceutical contamination in freshwater ecosystems and protecting benthic biodiversity and ecosystem functions.
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ANALYTICAL SCIENCES
·
2021
·Vol. 37
·期 11
·1525-1531
·
IF 2.081
Zhifang DING,Yue LI,Ying BAO,Kexin HAN,Iparguli TUREPU,Guixin LI
A signal-on supersandwich type of electrochemiluminescence (ECL) DNA biosensor was developed based on the poly(aniline-luminol) nanowires (PALNWs) modified electrode and enhancement of ferrocene (Fc) on ECL of luminol. Aminated capture DNA was covalently linked to the PALNWs on the electrode surface by the crosslinking of glutaraldehyde. In presence of target DNA, its 3′ terminus hybridizes with the capture probe and the 5′ terminus hybridizes with ferrocene labeled DNA (Fc-DNA) to form a long DNA concatamer supersandwich structure. The ECL intensity of the prepared biosensor was clearly improved by increasing the concentration of target DNA due to the enhancement of ferrocene on luminol ECL. The difference of the ECL intensity in the absence and presence of target DNA was used to monitor the hybridization event. The difference of ECL linearly increased with the logarithm of target DNA concentration in the range from 1.0 × 10−16 – 1.0 × 10−8 mol L−1 with a detection limit of 5.8 × 10−17 mol L−1. The sensor had high sensitivity and wide linear relationship for the detection of target DNA.
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APPLIED ORGANOMETALLIC CHEMISTRY
·
2018
·Vol. 32
·期 8
·e4423
·
IF 3.581
XueWen Liu,Jie Huang,YuXuan Tang,YouMing Shen,JiLin Lu
A new polypyridyl ligand containing a nitro group and two new ruthenium complexes of it were synthesized. The two complexes exhibited non-dppz DNA ‘light switch’ effects after interaction with calf thymus DNA. Introducing both electron-withdrawing group (─ NO 2 ) and electron-donating group (─ CH 3 ) may be the reason that the two complexes display DNA ‘light switch’ behaviors. Furthermore, one of the complexes showed higher photocleavage activity, topoisomerase I inhibition activity and DNA affinity than the other. The present work shows that the more active complex can be employed as a non-dppz DNA ‘light switch’, DNA photocleaver and topoisomerase I inhibitor. In addition, the two complexes have no or weak cytotoxic activities against Eca-109 and A549 cells.
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ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
M.S. Bacchu,M.R. Ali,S. Das,S. Akter,H. Sakamoto,S.-I. Suye,M.M. Rahman,K. Campbell,M.Z.H. Khan
An efficient platform for the detection of Salmonella enterica serovar Typhi ( S. Typhi ) is essential for early-stage diagnosis of typhoid to prevent and contain outbreaks. Here, we fabricated an electrochemical DNA biosensor for selective identification of S. Typhi in real samples. The biosensor has been fabricated by immobilizing an amine labelled S. Typhi specific single-strand capture probe on the surface of gold nanoparticles (AuNP) and poly cysteine (P-Cys) modified screen-printed electrode. Differential pulse voltammetry (DPV) of anthraquinone-2-sulfonic acid monohydrate sodium salt (AQMS) as a signal indicator was monitored to detect S. Typhi by hybridization of target DNA with the probe DNA . The fabricated biosensor shows a detection range of 1 × 10 −6 to 1 × 10 −22 molL −1 with a LOD of 6.8 × 10 −25 molL −1 in S. Typhi complementary linear target and 1.8 × 10 5 to 1.8 CFUml −1 with a LOD of 1 CFUml −1 in a real S. Typhi sample. The biosensor shows excellent discrimination ability to some bases mismatched and different bacterial cultures (same and distant genera). The most beneficial points of the proposed DNA biosensor are the lower limit of detection and the ability to reuse the biosensor more than 6 to 7 times. In addition, the practicability of the biosensor was investigated via detecting S. Typhi in blood, poultry feces, egg, and milk whereby excellent recoveries ranging from 96.54 to 103.47% were demonstrated indicating that this biosensor might be the most promising diagnostic tool for monitoring S . Typhi in clinical and food samples.
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Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Fangfang Wang,Sora Jin,Franklin Mayca Pozo,Danmei Tian,Xiyang Tang,Yi Dai,Xinsheng Yao,Jinshan Tang,Youwei Zhang
DNA damage response (DDR) is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs. Hence, small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy. Through a recent chemical library screen, we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins. Mechanistically, shikonin inhibited the activation of ataxia telangiectasia mutated (ATM), and to a lesser degree ATM and RAD3-related (ATR), two master upstream regulators of the DDR signal, through inducing degradation of ATM and ATR-interacting protein (ATRIP), an obligate associating protein of ATR, respectively. As a result of DDR inhibition, shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models. While degradation of ATRIP is proteasome dependent, that of ATM depends on caspase- and lysosome-, but not proteasome. Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs. These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin. Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.
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MEASUREMENT
·
2025
·
IF 5.6
Xu-guang Hu,Zhan-kun Li,Ju-wei Zhang,Xi-xin Wang,Xiao-ming Chen,Yong Zhao
A label-free fiber-optic optofluidic biosensor integrated into microfluidic chip based on vernier effect is proposed for the specific and high-sensitivity detection of DNA molecules, which is made up of a Michelson interferometer (MI) and a Fabry Perot interferometer (FPI) in parallel. The MI is prepared by a single-hole dual-core micro-structured fiber (MOF) with a suspended core attached to the hole serving as the sensing arm, and used as the sensing element. A micropore is etched directly above the microchannel of MI as the fluid inlet by femtosecond laser processing, and integrated into the microfluidic chip for sample replacement. The detection volume is only nanoliters and the sample can be quickly replaced within seconds. The experimental findings indicate that the proposed optofluidic sensor shows a high refractive index (RI) sensitivity of −8791 nm/RIU and has an ultra-low detection limit of 7.45 × 10 −6 RIU within the range of 1.3328–1.3370. By immobilizing probe DNA (pDNA) molecules on the suspended core through surface functionalization, the optofluidic sensor enables label-free detection of 1 μM complementary DNA (cDNA) solution and shows excellent specificity. The proposed fiber optofluidic biosensor has great development prospects in ultra-low volume and high-sensitivity detection of biomolecules.
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