The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.

The initiation of cell division integrates a large number of intra- and extracellular inputs. D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication1. Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. Accordingly, increased levels and activity of cyclin D-CDK4/6 complexes are strongly linked to unchecked cell proliferation and cancer2,3. However, the mechanisms that regulate levels of cyclin D are incompletely understood4,5. Here we show that autophagy and beclin 1 regulator 1 (AMBRA1) is the main regulator of the degradation of cyclin D. We identified AMBRA1 in a genome-wide screen to investigate the genetic basis of  the response to CDK4/6 inhibition. Loss of AMBRA1 results in high levels of cyclin D in cells and in mice, which promotes proliferation and decreases sensitivity to CDK4/6 inhibition. Mechanistically, AMBRA1 mediates ubiquitylation and proteasomal degradation of cyclin D as a substrate receptor for the cullin 4 E3 ligase complex. Loss of AMBRA1 enhances the growth of lung adenocarcinoma in a mouse model, and low levels of AMBRA1 correlate with worse survival in patients with lung adenocarcinoma. Thus, AMBRA1 regulates cellular levels of cyclin D, and contributes to cancer development and the response of cancer cells to CDK4/6 inhibitors.

A spatiotemporal barrier formed by Follistatin is required for left-right patterning.

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Superb Microvascular Imaging for the Differentiation of Benign and Malignant Breast Lesions: A System Review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic performance of SMI in the diagnosis of benign and malignant breast lesions. METHODS: A systematic search of PubMed, EMBASE, Cochrane, OVID, SCI, and SCOPUS was performed to find relevant studies which applied SMI to differentiate benign and malignant breast lesions. All the studies were published before October 10, 2022. Only studies published in English were collected. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to assess the quality of the included studies. Summary receiver operating characteristic (SROC) modeling was also performed to the diagnostic performance of SMI in the diagnosis of benign and malignant breast lesions. Subgroup analyses and meta-regression were performed to find out the heterogeneity. RESULTS: Twenty studies which include a total of 2873 lesions (1748 benign and 1125 malignant) in 2740 patients were evaluated in this meta-analysis. The summary sensitivity and specificity were 0.82 (95% confidence interval [CI]: 0.76-0.86), 0.70 (95% CI: 0.64-0.76) for SMI vascular degree, 0.77 (95% CI: 0.67-0.84), 0.79 (95% CI: 0.75-0.83) for SMI vascular distribution, 0.78 (95% CI: 0.70-0.84), 0.75 (95% CI: 0.69-0.80) for SMI vascular morphology, 0.81 (95% CI: 0.72-0.87), 0.80 (95% CI: 0.75-0.85) SMI penetration vessel. For SMI overall vascular features, the summary sensitivity and summary specificity were 0.74 (95% CI: 0.61-0.84) and 0.80 (95% CI: 0.76-0.84). The result of subgroup analysis and meta-analysis showed malignant rate and country might be the cause of heterogeneity of diagnostic accuracy of vascular grade and morphology. CONCLUSION: SMI vascular features have high sensitivity and specificity in the differentiation of benign and malignant lesions. Future international multicenter studies in various regions with large sample size are required to confirm these findings.

CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.

Multi-subunit cullin-RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4AMBRA1 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4AMBRA1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5SOCS3 and HIV-1 CRL5VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4AMBRA1 modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5SOCS3 and CRL5VIF, respectively. Thus, by discovering a substrate of CRL4AMBRA1, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Binding Kinetics Toolkit for Analyzing Transient Molecular Conformations and Computing Free Energy Landscapes.

Understanding ligand binding kinetics and thermodynamics, which involves investigating the free, transient, and final complex conformations, is important in fundamental studies and applications for chemical and biomedical systems. Examining the important but transient ligand-protein-bound conformations, in addition to experimentally determined structures, also provides a more accurate estimation for drug efficacy and selectivity. Moreover, obtaining the entire picture of the free energy landscape during ligand binding/unbinding processes is critical in understanding binding mechanisms. Here, we present a Binding Kinetics Toolkit (BKiT) that includes several utilities to analyze trajectories and compute a free energy and kinetics profile. BKiT uses principal component space to generate approximated unbinding or conformational transition coordinates for accurately describing and easily visualizing the molecular motions. We implemented a new partitioning approach to assign indexes along the approximated coordinates that can be used as milestones or microstates. The program can generate input files to run many short classical molecular dynamics simulations and uses milestoning theory to construct the free energy profile and estimate binding residence time. We first validated the method with a host-guest system, aspirin unbinding from ß-cyclodextrin, and then applied the protocol to pyrazolourea compounds and cyclin-dependent kinase 8 and cyclin C complexes, a kinase system of pharmacological interest. Overall, our approaches yielded good agreement with published results and suggest ligand design strategies. The computed unbinding free energy landscape also provides a more complete picture of ligand-receptor binding barriers and stable local minima for deepening our understanding of molecular recognition. BKiT is easy to use and has extensible features for future expansion of utilities for postanalysis and calculations.

Harnessing Shape Complementarity for Upgraded Cyclohexane Purification through Adaptive Bottlenecked Pores in an Imidazole-Containing MOF.

Shape complementarity is a biological craft for precisely binding substrates at protein-protein interfaces. An analogy to such a function can be drawn conceptually for crystalline porous solids; yet the manifested entities are rare in reticular chemistry. The bottleneck-shaped pores carved out of a metal-organic framework, Zn(MIBA)2 (aka. MAF-stu-13), can perfectly accommodate benzene molecules. Remarkably, its framework adapts to the optimal guest binding-the enhanced host-guest interactions in the neck in turn minimize the guest-guest repulsion in the pore to the extent it turns into attraction-as demonstrated by the combined X-ray structural and DFT computational studies. This adaptive material can be used for liquid-phase production of ultrahigh-purity (≥99 %) cyclohexane, achieving a balance between uptake capacity and separation selectivity and surpassing the performances of other porous and nonporous crystals reported recently (e.g. product purity 99.4 % vs. 97.5 % to date).

Genetic interaction mapping in mammalian cells using CRISPR interference.

We describe a combinatorial CRISPR interference (CRISPRi) screening platform for mapping genetic interactions in mammalian cells. We targeted 107 chromatin-regulation factors in human cells with pools of either single or double single guide RNAs (sgRNAs) to downregulate individual genes or gene pairs, respectively. Relative enrichment analysis of individual sgRNAs or sgRNA pairs allowed for quantitative characterization of genetic interactions, and comparison with protein-protein-interaction data revealed a functional map of chromatin regulation.

Smad3-mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial-mesenchymal transition.

During epithelial-mesenchymal transition (EMT), reprogramming of gene expression is accompanied by histone modifications. Whether EMT-promoting signaling directs functional changes in histone methylation has not been established. We show here that the histone lysine methyltransferase SETDB1 represses EMT and that, during TGF-ß-induced EMT, cells attenuate SETDB1 expression to relieve this inhibition. SETDB1 also controls stem cell generation, cancer cell motility, invasion, metastatic dissemination, as well as sensitivity to certain cancer drugs. These functions may explain the correlation of breast cancer patient survival with SETDB1 expression. At the molecular level, TGF-ß induces SETDB1 recruitment by Smad3, to repress Smad3/4-activated transcription of SNAI1, encoding the EMT "master" transcription factor SNAIL1. Suppression of SNAIL1-mediated gene reprogramming by SETDB1 occurs through H3K9 methylation at the SNAI1 gene that represses its H3K9 acetylation imposed by activated Smad3/4 complexes. SETDB1 therefore defines a TGF-ß-regulated balance between histone methylation and acetylation that controls EMT.

Antioxidant and Compositional HPLC Analysis of Three Common Bamboo Leaves.

Bamboo leaves of Phyllostachys nigra (PN), Lophatherum gracile (LG), and Pleioblastus amarus (PA) are three common herbs in China. In this work, a new high performance liquid chromatography (HPLC) method for the simultaneous determination of seven compounds in bamboo leaves has been developed; and PN, LG, and PA leaves were analyzed. PN showed four times as much chlorogenic acid (CA) than the other two, and contained the most isoorientin (iso-ORI) and isovitexin (iso-VIT) as well. The PA presented the most orientin (ORI) and LG covered a majority of cynaroside (CYN). We measured the antioxidant activity by scavenging the stable 2,2-diphenyl-1-pyridinohydrazinyl (DPPH) free radicals, and found that Luteolin (inhibitory concentration (IC)50 = 0.42 µM, LUT) and CYN (IC50 = 0.43 µM) showed 2-3 times higher antioxidant activity than iso-ORI (IC50 = 0.81 µM), ORI (IC50 = 0.84 µM), and other related antioxidant standards such as trolox (IC50 = 0.97 µM) and ascorbic acid (IC50 = 0.93 µM, VC). Among extracts, PN and PA showed considerable antioxidant activity, which was related well with the contents of CA, iso-ORI, and iso-VIT (p < 0.05). This study firstly provides evidence for functional antioxidant compounds of bamboo leaves based on statistical analysis of the HPLC analysis and DPPH assay, and it lays a foundation for its further development or utilization.

[Research progress of liver injury induced by Polygoni Mulitiflori Radix].

Polygoni Mulitiflori Radix, or dried root tuber of Polygonum multiflorum(PM), is a traditional Chinese tonic medicine, with the effect in nourishing liver and kidney, and benefiting blood essence and hair. It is widely used in clinical and healthcare products. In recent years, more and more reports about adverse reactions of root tuber of P.multiflorum and its preparations have been reported. Fortunately, there is also substantial progress in the experimental study on liver injury induced by PM. According to the literature review, the possible causes of liver injury were found to be the mixture of raw and processed PM and long-term high-dose administration. In addition, the liver injury induced by PM is idiosyncratic liver injury, and individual factors are also the important cause. At the same time, according to the literature reports, the effects of chemical components in different pathological animal models were summarized, finding that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside was the main component for liver injury; based on the clinical manifestations of liver injury induced by PM, the effects of some chemical components on bilirubin and bile acid metabolism were analyzed. This paper reviews the study progress of liver injury induced by PM.

Protamine-gold nanoclusters as peroxidase mimics and the selective enhancement of their activity by mercury ions for highly sensitive colorimetric assay of Hg(II).

We certify that protamine-gold nanoclusters (PRT-AuNCs) synthesized by one-pot method exhibit peroxidase-like activity. The catalytic activity of PRT-AuNCs followed typical Michaelis-Menten kinetics and exhibited higher affinity to 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate compared to that of natural horseradish peroxidase. Meanwhile, we found that Hg(II) could dramatically and selectively enhance the peroxidase-like activity of PRT-AuNCs, and the enhanced mechanism by Hg(II) was demonstrated to be generation of the cationic Au species and the partly oxidized Au species (Auδ+) by Hg2+-Au0/Au+ interaction. Based on this finding, quantitative determinations of Hg(II) via visual observation and absorption spectra were achieved. The proposed strategy displays high selectivity that arises from the strong aurophilic interaction of mercury towards gold. Moreover, the developed method is highly sensitive with a wide linear range and low detection limit of 1.16 nM. This strategy is not only helpful to develop effective nanomaterials-based artificial enzyme mimics but also irradiative to discover new applications of artificial mimic enzymes in bio-detection, medical diagnostics, and biotechnology. Graphical abstract Protamine-gold nanoclusters (PRT-AuNCs) synthesized by one-pot method exhibit peroxidase-like activity. Hg(II) can stimulate the peroxidase-like activity of PRT-AuNCs selectively, enhancing their ability to catalyze the chromogenic reaction of TMB by H2O2.

Protamine-stabilized gold nanoclusters as a fluorescent nanoprobe for lead(II) via Pb(II)-Au(I) interaction.

The authors report on a one-pot approach for synthesizing highly fluorescent protamine-stabilized gold nanoclusters. These are shown to be a viable nanoprobe for selective and sensitive fluorometric determination of lead(II) via quenching of fluorescence via Pb(II)-Au(I) interaction. Under optimized conditions, fluorescence measured at excitation/emission peaks of 300/599 nm drops in the 80 nM-15 µM lead(II) concentration range. The detection limit is 24 nM, and relative standard deviations (for n = 11) at concentrations of 0.10, 4.0 and 15 µM are 1.6, 2.5 and 1.9%, respectively. The relative recoveries of added lead(II) in the water samples ranged from 97.9 ± 2.29% to 101.2 ± 1.83%. Graphical abstract Lead(II) ions are found to be able to selectively and sensitively quench the fluorescence of the protamine-gold nanoclusters (PRT-AuNCs). Thereby, an inexpensive, selective and sensitive lead(II) assay was established.

Peritoneal dialysis reduces amyloid-beta plasma levels in humans and attenuates Alzheimer-associated phenotypes in an APP/PS1 mouse model.

Clearance of amyloid-beta (Aß) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aß clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aß, suggesting that the peripheral approach of removing Aß from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aß burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aß concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from 6 months of age (prevention study) or 9 months of age (treatment study). The Aß in the interstitial fluid (ISF) was collected using microdialysis. Behavioural performance, long-term potentiation (LTP), Aß burden and other AD-type pathologies were measured after 1 month of peritoneal dialysis. Peritoneal dialysis significantly reduced plasma Aß levels in both CKD patients and APP/PS1 mice. Aß levels in the brain ISF of APP/PS1 mice immediately decreased after reduction of Aß in the blood during peritoneal dialysis. In both prevention and treatment studies, peritoneal dialysis substantially reduced Aß deposition, attenuated other AD-type pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, and synaptic dysfunction, and rescued the behavioural deficits of APPswe/PS1 mice. Importantly, the Aß phagocytosis function of microglia was enhanced in APP/PS1 mice after peritoneal dialysis. Our study suggests that peritoneal dialysis is a promising therapeutic method for AD, and Aß clearance using a peripheral approach could be a desirable therapeutic strategy for AD.

A multifunctional fluorescent aptamer probe for highly sensitive and selective detection of cadmium(II).

We report a highly sensitive and selective strategy for Cd(II) assay using a singly labeled multifunctional probe consisting of a Cd(II)-specific aptamer (CAP), which acted as a recognition element for Cd(II) and a signal reporter. The presence of Cd(II) can induce the conformational switching of the CAP, accompanied by a change in fluorescence intensity. Thereby, a fluorescence strategy for Cd(II) assay was established. The proposed method has a detection limit of 2.15 nM, which is much lower than the detection limits reported in related literature. This strategy involves only an aptamer probe, and the use of such a G4-based quencher avoids the dual labeling of the CAP with fluorophore/quencher units. It is obviously more convenient and economical than the other aptamer-based biosensors for Cd(II) detection. The mechanism by which Cd(II) induces the CAP to change from a random coil sequence to a stem-loop structure was studied in a series of control experiments. This strategy would be helpful in the design of a sensitive analytical platform for various target assays in environmental and biomedical fields. Graphical Abstract The presence of Cd2+ leads to the conformational change of CAP from a random coil sequence to a stem-loop structure, resulting in a quenching in the fluorescence.

Polarization charge: Theory and applications to aqueous interfaces.

When an electric field is applied across an interface, a dielectric will acquire a polarization charge layer, assumed infinitely thin in the theory of macroscopic dielectrics and also in most treatments of electrokinetic phenomena in nanoscale structures. In this work we explore the polarization charge layer in molecular detail. Various formal relations and a linear response theory for the polarization charge are presented. Properties of the polarization charge layer are studied for three aqueous interfaces: air-water, a crystalline silica surface with water, and an amorphous silica surface with water. The polarization charge is calculated from equilibrium simulations via linear response theory and from non-equilibrium simulations, and the results are within statistical error. The polarization charge is found to be distributed within a region whose width is on the order of a nanometer.

Downregulation of selenium-binding protein 1 is associated with poor prognosis in lung squamous cell carcinoma.

BACKGROUND: We found that selenium-binding protein 1 (SBP1) was progressively decreased in the human bronchial epithelial carcinogenic processes. Knockdown of SBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. However, the relationship between SBP1 expression and clinicopathological factors of patients has not been defined completely. The specific role of SBP1 in prognosis of lung squamous cell carcinoma (LSCC) is still unknown. METHODS: Tissue samples from 82 patients treated by pulmonary lobectomy for LSCC were used. Immunohistochemistry and western blotting were used to detect the expressions of SBP1 protein. The relationships between the expression level of SBP1 and the clinicopathological features of patients were analyzed. Cox proportional hazard regression analysis and Kaplan-Meier method were used to perform survival analysis. RESULTS: Expressions of SBP1 proteins were significantly lower in LSCC tissues than that in the corresponding normal bronchial epithelium (NBE) tissues (P = 0.000). In LSCC, The expression levels of SBP1 had not correlated with patients' age, gender, smoking state, primary tumor stages (T), TNM clinical stages, and distant metastasis (M) (P > 0.05). However, downregulation of SBP1 was significantly associated with higher lymph node metastasis and lower overall survival rate (P < 0.05). Cox regression analysis indicated low expressions of SBP1 can be an independent prognostic factor for poor overall survival in LSCC patients (P = 0.002). CONCLUSIONS: Downregulation of SBP1 may play a key role in the tumorigenic process of LSCC. SBP1 may be a novel potential prognostic factor of LSCC.

A colorimetric aptasensor for the highly sensitive detection of 8-hydroxy-2'-deoxyguanosine based on G-quadruplex-hemin DNAzyme.

A highly sensitive, low-cost colorimetric aptasensor was developed for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urine. The method is based on a conformational switching of the 8-OHdG aptamer to form a G-quadruplex structure in the presence of 8-OHdG. The resulting G-quadruplex assembles into a peroxidase-like DNAzyme with hemin, which effectively catalyzes the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(2-)) by H2O2 to ABTS(+), resulting in an increase in the absorption signal at 416nm along with a color change of the solution. The response signals linearly correlated with the concentration of 8-OHdG, ranging from 466pM to 247nM with a detection limit of 141pM. The relative standard deviation and the recovery were 1.97-3.47% (n=11) and 98.8-100.2%, respectively. The proposed method avoids the label and derivatization steps in common methods and allows direct analysis of the samples by the naked eye without costly instruments, which is reliable, inexpensive, and sensitive.