CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Yuqing Zhu,Xiaohe Zheng,Rui Zhu,Hongrui Zhao,Hongli Zhai,Feiyang Qian,Tenghua Zhang,Zihui Xie,Silan Liu,Bowen Jiang,Yan Sheng,Jiaming Hu
Detection of multiple biomarkers for accurate diagnosis of disease is highly desirable but remains challenging. Here, we developed a versatile diagnostic biosensor (SMARTLOCK) through the unique combination of DNA tetrahedron, nonlinear HCR and CRISPR-Cas12a system for simultaneous detection of multiple nucleic acids, small molecules, proteins and different types of combinations. Two DNA tetrahedrons are assembled into a functional dumbbell lock, which was unlocked by the target molecules, thereby triggering a two-stage signal amplification of nonlinear HCR and CRISPR-Cas12a to generate powerful fluorescence signals. The capability of multi-target simultaneous detection of SMARTLOCK is demonstrated in the detection of miR-141, miR-375, miR-21, ATP, cortisol, insulin and their combinations. SMARTLOCK could selectively (specificity = 93.3%) and sensitively (sensitivity = 90%) distinguish early-stage prostate cancer (PCa) patients (n = 10) from healthy donors (n = 30). Measurement of two PCa-related RNAs (miR-141 and miR-375) shows the potential of SMARTLOCK to be a highly accurate and low-cost tool for the screening, diagnosis and prognosis of various diseases.
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Journal of Materials Chemistry A
·
2023
·Vol. 11
·期 43
·23376-23386
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IF 11.9
Xiaohui Niu,Rui Zhao,Yongqi Liu,Mei Yuan,Hongfang Zhao,Hongxia Li,Xing Yang,Hui Xu,Kunjie Wang
Biomimetic chiral metal organic frameworks (BioMOFs) act as chiral selectors to recognize and sense chiral molecules mimicking biological functional systems, providing a novel perspective for chiral recognition in natural processes. Here, a biological chiral metal–organic framework has been successfully prepared, namely ZnBTCHx (BTC = 1,3,5-benzenetricarboxylic acid, Hx = hypoxanthine), which has periodic large and small grooves similar to the double helix structure of DNA. The adaptability of the local shape of ZnBTCHx can facilitate specific recognition of the chiral guest. The tryptophan (Trp) enantiomer enters the main groove of ZnBTCHx as a guest, and the ZnBTCHx groove selectively recognizes L- and D-Trp because the size and shape of the Trp enantiomer match the groove of ZnBTCHx and it fits snugly into the primary groove. The way in which L-/D-Trp binds to ZnBTCHx reveals key molecular interactions that confer host–guest binding specificity, including π–π interactions as well as hydrogen bonding between chiral host and guest molecules, and spatial adaptation.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
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IF 9.8
Hongmei Zou,Mingxuan Zhang,Jin Chen,Stanley Aniagu,Yan Jiang,Tao Chen
Benzo[ a ]pyrene (BaP) is a representative polycyclic aromatic hydrocarbon widely present in the environment. We previously reported that the aryl hydrocarbon receptor (AHR) mediates BaP-induced apoptosis and cardiac malformations in zebrafish embryos, but the underlying molecular mechanisms were unclear. Since BaP is a mutagenetic compound, we hypothesize that BaP induces apoptosis and heart defects via AHR-mediated DNA damage. In this study, zebrafish embryos were exposed to BaP at a concentration of 0.1 μM from 2 to 72 h post fertilization, either with or without inhibitors/agonists. AHR activity and levels of reactive oxygen species (ROS) were examined under a fluorescence microscope. mRNA expression levels were quantified by qPCR. DNA damage and apoptosis were detected by immunofluorescence. Our findings revealed that BaP exposure significantly increased BPDE-DNA adducts, mitochondrial damage, apoptosis and heart defects in zebrafish embryos. These effects were counteracted by inhibiting AHR/cyp1a1 using pharmaceutical inhibitors or genetic knockdown. Furthermore, we observed that spironolactone, an antagonist of nucleotide excision repair (NER), significantly enhanced BaP-induced BPDE-DNA adducts, mitochondrial damage, apoptosis and heart malformation rates. Conversely, SRT1720, a SIRT1 agonist, reduced the adverse effects of BaP. Supplementation with spironolactone also enhanced γ-H2AX signals in the heart of zebrafish embryos exposed to BaP. Additional experiments demonstrated that BaP suppressed the expression of SIRT1. We further established that AHR, when activated by BaP, directly inhibited SIRT1 transcription, leading to downregulation of XPC and XPA, which are essential NER genes involved in the recognition and verification steps of the NER process. Taken together, our results indicate that AHR mediates BaP-induced DNA damage in the heart of zebrafish embryos by inducing BPDE-DNA adduct formation via the AHR/Cyp1a1 signalling pathway, as well as suppressing NER via AHR-mediated inhibition of SIRT1.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2021
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IF 4.098
Lingyuan Liu,Qianyi Zhang,Feng Li,Mei Wang,Jing Sun,Shuyun Zhu
Herein, fluorescent DNA-templated silver nanoclusters (DNA-AgNCs) with red emission were synthesized and utilized as novel probe to detect D-penicillamine (D-Pen) for the first time. D-Pen molecules contain a thiol which can combine with Ag to form a non-fluorescent ground state complex, inducing the aggregation of DNA-AgNCs followed by the fluorescence quenching. The quenching mechanism is well-studied and found to be a static quenching process. This method can detect D-Pen in the range of 0.025–0.7 μM with the detection limit as low as 8 nM, which is 1–3 orders of magnitude more sensitive than those based on other fluorescent nanoprobes. More importantly, the preparation procedure for DNA-AgNCs is fast and without the requirement of heavy metal ions. Thus, this detection strategy is time-saving and eco-friendly. Satisfactory recoveries have been acquired for monitoring D-Pen in human serum samples and pharmaceutical samples owing to the high sensitivity.
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2021
·Vol. 28
·期 23
·30101-30110
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IF 4.223
Bian Xiaoxue,Gao Yongfei
An unexplored attributing molecular mechanism of Cd toxicity is interference with the epigenetic machinery, such as DNA methylation, processes that are crucial for early fetal development. In order to investigate the effects of Cd on the expression of metallothionein (MT) and Dnmts transcripts, markers of DNA methylation, and signaling pathway gene expression, zebrafish embryos were exposed during 24 hours post-fertilization (starting at maximum 8-cell stage) to 0.0089, 0.089, and 0.89 μM Cd. The results showed that the Cd accumulation in zebrafish embryo reached a stable level after 12 hpf, and the Cd accumulation at individual time points was significantly different among different concentration groups. MT mRNA fold was significantly positive with the Cd content in embryos. We observed that the expression level of DNA methyltransferase ( Dnmts ) in the 0.089 μM Cd exposure group was significantly up-regulated. Dnmt1 expression was significantly up-regulated in the 0.89 μM Cd exposure group, and Dnmt3s expression and global methylation levels were significantly down-regulated. Cd up-regulated ErbB-3 gene expression, down-regulated ErbB-4 gene expression, and neutralized ErbB-1 gene expression. Cd activated Ca 2+ , MAPK-JUK , p38 MAP kinase, PI3K-AKT , and VEGF signaling pathway genes, indicating these pathway genes related to Cd exposure level. The results are helpful to clarify the molecular mechanism of DNA methylation in zebrafish embryo under metal pressure and further interference with the epigenetic machinery.
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ACS Sensors
·
2021
·
IF 7.711
Guangyu Tao,Xiao Xu,Rong Sheng Li,Feng Liu,Na Li
Restriction endonucleases (ENases) and DNA methyltransferases (MTases) are important enzymes in biological processes, and detection of ENases/MTases activity is significant for biological and pharmaceutical studies. However, available nonamplification methods with a versatile design, desirable sensitivity, and signal production mode of unbiased quantification toward multiple nucleases are rare. By combining deliberately designed hairpin DNA probes with the colocalized particle counting technique, we present a nonamplification, separation-free method for multiplexed detection of ENases and MTases. In the presence of target ENases, the hairpin DNA is cleaved and the resulting DNA sequence forms a sandwich structure to tie two different-colored fluorescent microbeads together to generate a colocalization signal that can be easily detected using a standard fluorescence microscope. The multiplexed assay is realized via different color combinations. For the assay of methyltransferase, methylation by MTases prevents cleavage of the hairpin by the corresponding ENase, leading to decreased colocalization events. Three ENases can be simultaneously detected with high selectivity, minimal cross-talk, and detection limits of (4.1–6.4) × 10–4 U/mL, and the corresponding MTase activity can be measured without a change of the probe design. The potential for practical application is evaluated with human serum samples and different ENase and MTase inhibitors with satisfactory results. The proposed method is separation-free, unbiased toward multiple targets, and easy to implement, and the strategy has the potential to be extended to other targets.
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Nature Communications
·
2021
·Vol. 12
·期 1
·1-12
·
IF 14.919
Chen Feng,Bai Min,Cao Xiaowen,Xue Jing,Zhao Yue,Wu Na,Wang Lei,Zhang Dexin,Zhao Yongxi
Exploring spatial organization and relationship of diverse biomolecules within cellular nanoenvironments is important to elucidate the fundamental processes of life. However, it remains methodologically challenging. Herein, we report a molecular recognition mechanism cellular macromolecules-tethered DNA walking indexing (Cell-TALKING) to probe the nanoenvironments containing diverse chromatin modifications. As an example, we characterize the nanoenvironments of three DNA modifications around one histone posttranslational modification (PTM). These DNA modifications in fixed cells are labeled with respective DNA barcoding probes, and then the PTM site is tethered with a DNA walking probe. Cell-TALKING can continuously produce cleavage records of any barcoding probes nearby the walking probe. New 3’-OH ends are generated on the cleaved barcoding probes to induce DNA amplification for downstream detections. Combining fluorescence imaging, we identify various combinatorial chromatin modifications and investigate their dynamic changes during cell cycles. We also explore the nanoenvironments in different cancer cell lines and clinical specimens. In principle, using high-throughput sequencing instead of fluorescence imaging may allow the detection of complex cellular nanoenvironments containing tens of biomolecules such as transcription factors.
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ANALYTICA CHIMICA ACTA
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2021
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IF 6.558
Jian Chu,Chun Chen,Xijian Li,Libing Yu,Wenjing Li,Mengxi Cheng,Wei Tang,Zhonghua Xiong
It is of great significance to develop facile and economical strategies for on-site detection and treatment of toxic metal ions . Stimulus-responsive DNA hydrogel materials have been increasingly used for convenient detection of metal ions due to their advantages such as simplicity, portability, and ease of storage. However, these methods still require encapsulation of signal tags by labeling or embedding. In this paper, a one-step preparation of Pb 2+ -responsive pure DNA hydrogel material was designed to realize a new label-free strategy for Pb 2+ biosensing. The Pb 2+ -dependent DNAzyme strand and substrate strand were introduced to fabricate the DNA hydrogel. The presence of Pb 2+ in the sample activates the enzyme strand in the hydrogel skeleton and triggers the cleavage of the substrate, thereby destroy the hydrogel structure. DNA fragments released by the collapsed hydrogel were readily measured as signal output for quantifying Pb 2+ concentrations with a minimum detection limit of 7.7 nM. We successfully eliminated the need for embedding or labeling of signal molecules by using the DNA molecules that construct hydrogels as the signal output. And the newly developed method for label-free detection of Pb 2+ based on pure DNA hydrogel is simple, easy readout, and cost-effective. By adjusting the DNAzyme and substrate sequences, label-free analysis of other metal ions can also be achieved. We expect that our strategy can be applied to the field detection of toxic metal ions.
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ACS Omega
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2021
·
IF 3.512
Hangjie Wu,Lide Gu,Xiaoyi Ma,Xueqing Tian,Shihui Fan,Mingcan Qin,Jing Lu,Mingsheng Lyu,Shujun Wang
Helicobacter pylori was first isolated from gastritis patients by Barry J. Marshall and J. Robin Warren in 1982, and more than 90% of duodenal ulcers and about 80% of gastric ulcers are caused by H. pylori infection. Most detection methods require sophisticated instruments and professional operators, making detection slow and expensive. Therefore, it is critical to develop a simple, fast, highly specific, and practical strategy for the detection of H. pylori. In this study, we used H. pylori as a target to select unique aptamers that can be used for the detection of H. pylori. In our study, we used random ssDNA as an initial library to screen nucleic acid aptamers for H. pylori. We used binding rate and the fluorescence intensity to identify candidate aptamers. One DNA aptamer, named HPA-2, was discovered through six rounds of positive selection and three rounds of negative selection, and it had the highest affinity constant of all aptamers tested (Kd = 19.3 ± 3.2 nM). This aptamer could be used to detect H. pylori and showed no specificity for other bacteria. Moreover, we developed a new sensor to detect H. pylori with the naked eye for 5 min using illumination from a hand-held flashlight. Our study provides a framework for the development of other aptamer-based methods for the rapid detection of pathogenic bacteria.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Daxiu Li,Xia Li,Fang Yang,Ruo Yuan,Yun Xiang
A protein-based therapy is significantly challenged by the successful delivery of native proteins into the targeted cancer cells. We address this challenge here using an all-sealed divalent aptamer tetrahedral DNA framework (asdTDF) delivery platform, in which the protein drug is encapsulated inside the cavity of the framework stoichiometrically via a reversible chemical bond. The ligase-assisted seal of the nicks results in highly enhanced TDF stability of the against nuclease digestion to effectively protect the therapeutic protein from degradation. In addition, the divalent aptamer sequences incorporated into the framework favor it with a target-specific and efficient delivery capability. Importantly, upon being readily delivered into the targeted cancer cells, endogenous glutathione can trigger the release of the native therapeutic protein from the TDF in a traceless fashion by cleaving the reversible chemical bond, thereby leading to effective apoptosis of the specific cancer cells.
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Nanoscale
·
2020
·Vol. 12
·期 35
·18249-18262
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IF 6.895
Bing Qin,Xiaoling Yuan,Mengshi Jiang,Hang Yin,Zhenyu Luo,Junlei Zhang,Chunqi Zhu,Xiang Li,Yingying Shi,Lihua Luo,Yongzhong Du,Jian You
Gene therapy mediated by non-viral carriers is gaining an increasing popularity due to its high biosafety and the convenience of production on a large scale, yet inefficient gene delivery is a limiting obstacle. Few gene vectors can avoid the endosome–lysosome route, and as a result, their DNA payloads are easily decomposed during transfection. Herein, a peptide (pardaxin, PAR)-modified cationic liposome (PAR-Lipo) targeting the endoplasmic reticulum (ER) was developed for improving the gene delivery efficiency. Interestingly, compared to non-PAR-modified cationic liposomes (Non-Lipos) and Lipofectamine 2000 (Lipo 2000, a commercial genetic vector), PAR-Lipos showed remarkably higher gene delivery efficiency in vitro and better antitumor efficacy in vivo. It was demonstrated that PAR-Lipos could be accumulated into the ER via a non-lysosome intracellular route after cellular internalization, which induced the retention of the DNA payload in the ER close to the nucleus, while Non-Lipos, like most conventional cationic carriers, mainly presented lysosomal retention after their endocytosis. The unique intracellular transport behavior of PAR-Lipos can enhance the protection of the DNA payload, prolong their residence time in the cell, and promote their entry into the nucleus relying on the intimate relationship between the ER and nuclear membrane, which is the explanation for the enhanced gene-therapy effect mediated by PAR-Lipos. Our research may provide alternative means of efficiently delivering genes in cells.
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Chemical Science
·
2020
·Vol. 11
·期 14
·3745-3751
·
IF 9.346
Wenting Zhou,Lei Wang,Can Liu,Qiuyi Teng,Zhaoyin Wang,Zhihui Dai
Quantification of circulating tumor DNA (ctDNA) is of great importance in liquid biopsy but difficult due to its low amount in bodily fluids. To meet this high demand, a novel method for ctDNA detection is established by quantifying cyclic DNA polymerization using lanthanide coordination polymers (Ln-CPs). Relying on the coordination between the pyrophosphate ion (PPi) and trivalent cerium ion (Ce3+), organic ligand-free PPi–Ce coordination polymer networks (PPi–Ce CPNs) with enhanced fluorescence are prepared for the first time. By surveying the optical properties of PPi–Ce CPNs, it is found that PPi regulates electric-dipole transition of Ce3+ to the lowest excited state, thus facilitating the emission of fluorescence. Therefore, fluorescence enhancement of PPi–Ce CPNs originates from the ligand field effect rather than the normal antenna effect. Moreover, a new strategy to quantify DNA polymerization is developed based on PPi–Ce CPNs. By introducing multifold cyclic DNA polymerization, a small amount of ctDNA triggers the exponential generation of PPi to form plenty of PPi–Ce CPNs. Accordingly, a biosensor is constructed for sensitive ctDNA detection by measuring the intense fluorescence of PPi–Ce CPNs. The biosensor is capable of sensing ctDNA at the sub-femtomolar level, which is far better than the analytical performances of commercial dyes. Besides, the analytical method is able to detect single nucleotide polymorphism and determine ctDNA in real samples. Considering that DNA polymerization is widely used in bio-recognition, bio-assembly and biomineralization, the work provides a versatile quantitative strategy of making relevant processes precise and controllable.
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