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1.
Adv Mater ; : e1906580, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32250001

RESUMO

In this study, a Cux OS@ZIF-8 nanostructure is fabricated to quantify the levels of hydrogen sulfide (H2 S) in living cells and in vivo. Zeolitic lmidazolate framework-8 (ZIF-8) is chosen as an encapsulation shell to improve the selectivity of this probe. Using this unique nanostructure, ultrasensitive quantification and bioimaging of H2 S in living cells are successfully achieved. The lower limit of detection is 0.8 and 5.3 nmol per 106 cells for circular dichroism and fluorescence modes, respectively. It is found that the chiral Cux OS NPs transformed into achiral Cux S NPs contribute to the ultrasensitive detection. Notably, this probe can also be carried out to detect and track H2 S levels in tumor-bearing animals. The discoveries put forward for the creation of a detection platform for quantitative tracking and analysis in clinic.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32119165

RESUMO

Cellular senescence is stress-induced, irreversible growth arrest, and is thought to impair tissue function. The clearance of senescent cells can delay the features of senescence. Herein, we report the development of plasmonic core-shell spiky nanorods (CSNRs) surface-modified with an anti-beta-2-microglobulin (aB2MG) antibody and triphenylphosphonium (TPP), to target the mitochondria in senescent cells. aB2MG-TPP@CSNRs irradiated with near-infrared (NIR) light selectively caused mitochondrial damage and apoptosis of senescent cells with relatively low NIR light power, and the ability of CSNRs to activate and amplify the immune response in vitro and in vivo was discovered. The photo-induced generation of reactive oxygen species (ROS) resulted in senescent-cell apoptosis and immune adjuvant effect by CSNRs accelerated the clearance of senescent cells in mice. This study opens the way for the use of precisely regulated plasmonic nanostructures for immune adjuvant and photo-induced apoptosis for age-related senescence.

3.
Analyst ; 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32222742

RESUMO

In this study, a gold immunochromatographic assay (GICA) based on a penicillin receptor protein (PBP) is proposed to simultaneously detect penicillin, cephalosporin, and carbapenem antibiotics in milk and chicken. A mutant PBP, carboxy-terminal of the ß-lactam sensor-transducer protein (BlaR-CTD, I188KS19CG24C) from Bacillus licheniformis ATCC14580 was expressed in E. coli as a soluble His-tag fusion protein. The purified BlaR-CTD mutant was labeled with colloidal gold (CG-BlaR-CTD-M) and applied to develop GICA. The GICA method was performed based on a competitive form, where the binding of the ampicillin-bovine serum albumin conjugate (Amp-BSA) to CG-BlaR-CTD-M was inhibited by free ß-lactams in samples. The performance of the assay was confirmed by analysis of milk and chicken samples. The limits of detection of 21 ß-lactam antibiotics met the maximum residue limits set by the European Union and China. The GICA gave results within 10 min, thus providing a rapid and reliable method for the on-site detection of multiple ß-lactams in milk and chicken samples.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32191832

RESUMO

In situ quantification and imaging of low-level intracellular microRNAs (miRs) are important areas in biosensor research. Herein, DNA-driven FexCuySe@upconversion nanoparticle (UCNP) core@satellite nanostructures were developed to probe microRNA-21 (miR-21). FexCuySe@UCNP probes displayed dual signals: upconversion luminescence (UCL) and magnetic resonance imaging (MRI). In the presence of miR-21, the luminescence signal was restored and the T2 value was significantly increased because of dissociation of UCNPs from the assemblies. There was a good linear relationship between the dual signals and the expression levels of miR-21 in the range of 0.035-31.824 amol/ngRNA. The limit of detection (LOD) was 0.0058 amol/ngRNA for the luminescence intensity and 0.0182 amol/ngRNA for the MRI signal. This method opens a new avenue for intracellular miR-21 detection with high sensitivity and specificity.

5.
Analyst ; 145(6): 2143-2151, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32129380

RESUMO

Tetrodotoxin (TTX) is a potent marine neurotoxin. Its frequent detection and widespread distribution pose a substantial health risk to consumers. The work presented herein describes the development of a lateral flow immunosensor based on a gold nanoparticle-labeled monoclonal antibody probe, which allows the affinity reaction of antigen-antibody and amplifies the reaction signal. The immunosensor assay was found to provide a visible limit of detection (vLOD) of 10 µg kg-1 in crucian and clam matrices without time-consuming pretreatment. Spiked samples were analyzed using the immunosensor and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The immunosensor gave average intra-assay recoveries of 84.0-103.9%, inter-assay recoveries of 76.1-105% for the crucian matrix and intra-assay recoveries of 78.5-93.0%, inter-assay recoveries of 74.8-85.7% for the clam matrix. The results obtained using the immunosensor and LC-MS/MS were in good agreement. The immunosensor test could be completed within 10 min, offering a convenient option or complementarity to the traditional methods of TTX detection.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32067302

RESUMO

The accumulation and deposition of ß-amyloid (Aß) plaques in the brain is considered a potential pathogenic mechanism underlying Alzheimer's disease (AD). Chiral l/d-Fex Cuy Se nanoparticles (NPs) were fabricated that interfer with the self-assembly of Aß42 monomers and trigger the Aß42 fibrils in dense structures to become looser monomers under 808 nm near-infrared (NIR) illumination. d-Fex Cuy Se NPs have a much higher affinity for Aß42 fibrils than l-Fex Cuy Se NPs and chiral Cu2-x Se NPs. The chiral Fex Cuy Se NPs also generate more reactive oxygen species (ROS) than chiral Cu2-x Se NPs under NIR-light irradiation. In living MN9D cells, d-NPs attenuate the adhesion of Aß42 to membranes and neuron loss after NIR treatment within 10 min without the photothermal effect. In-vivo experiments showed that d-Fex Cuy Se NPs provide an efficient protection against neuronal damage induced by the deposition of Aß42 and alleviate symptoms in a mouse model of AD, leading to the recovery of cognitive competence.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32109745

RESUMO

In this study, haptens were designed to produce highly sensitive and specific monoclonal antibodies (mAb) against carbamazepine (CBZ) and its metabolite carbamazepine-10, 11-epoxide (CBZ-EP). According to the results of our competitive enzyme-linked immunosorbent assay (ic-ELISA), the half-maximum inhibitory concentration values for anti-CBZ and anti-CBZ-EP mAb were 0.18 and 0.59 ng/mL, respectively. An immunochromatographic assay (ICA) was developed for the determination of CBZ and CBZ-EP concentrations. This method can provide visible limits of detection ranging from 0.25 to 1 ng/mL, and cut-off limits ranging from 5 to 10 ng/mL, and takes 10 min to evaluate with the naked eye. Importantly, these observations were consistent with those obtained by ic-ELISA and liquid chromatography-mass spectrometry. The ICA assay represented a reliable, fast, and high-throughput method for the determination of CBZ and CBZ-EP in serum samples.


Assuntos
Anticorpos Monoclonais/química , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Imunoensaio/métodos , Anticorpos Imobilizados/química , Anticorpos Imobilizados/metabolismo , Anticorpos Monoclonais/metabolismo , Carbamazepina/isolamento & purificação , Carbamazepina/metabolismo , Cromatografia Líquida , Humanos , Limite de Detecção , Modelos Lineares
8.
Top Curr Chem (Cham) ; 378(1): 18, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009187

RESUMO

DNA molecules with superior flexibility, affinity and programmability have garnered considerable attention for the controllable assembly of nanoparticles (NPs). By controlling the density, length and sequences of DNA on NPs, the configuration of NP assemblies can be rationally designed. The specific recognition of DNA enables changes to be made to the spatial structures of NP assemblies, resulting in differences in tailorable optical signals. Comprehensive information on the fabrication of DNA-driven NP assemblies would be beneficial for their application in biosensing and bioimaging. This review analyzes the progress of DNA-driven NP assemblies, and discusses the tunable configurations determined by the structural parameters of DNA skeletons. The collective optical properties, such as chirality, fluorescence and surface enhanced Raman resonance (SERS), etc., of DNA-driven NP assemblies are explored, and engineered tailorable optical properties of these spatial structures are achieved. We discuss the development of DNA-directed NP assemblies for the quantification of DNA, toxins, and heavy metal ions, and demonstrate their potential application in the biosensing and bioimaging of tumor markers, RNA, living metal ions and phototherapeutics. We hihghlight possible challenges in the development of DNA-driven NP assemblies, and further direct potential prospects in the practical applications of macroscopical materials and photonic devices.


Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Nanopartículas/química , Imagem Óptica/métodos , Biomarcadores Tumorais/análise , Grafite/química , Humanos , Metais/química , Análise Espectral Raman
9.
Adv Mater ; : e2000184, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100405

RESUMO

Senescence is a state of stable cell cycle arrest that can escape apoptosis and lead to aging and numerous age-related diseases. In this study, an upconversion-nanoparticle (UCNP)-centered Au20 -Au30 nanoparticles tetrahedron (UAuTe) is prepared by DNA hybridization, which can selectively accelerate the clearance of senescent cells. When the beta-2-microglobulin antibody (anti-B2MG) on the Au NPs recognizes senescent cells, the application of near-infrared (NIR) light induces the disassembly of the UAuTe by breaking the boronic ester linkage. Subsequently, the Granzyme B exposed on the UCNPs induces apoptosis in senescent cells, which can then be tracked by changes in fluorescence. It is found that, as compared to single Granzyme B, the UAuTe can not only control the Granzyme B delivery by NIR-responsivity, but also synergistically target and activate the Granzyme B in the senescent cell without the need of perforin. Moreover, this tool is applied successfully in vivo; the results demonstrate that the NIR-responsive tetrahedron can restore renal function, tissue homeostasis, fur density, and athletic ability in a mouse model of senescence after 30 d of treatment. The NIR-induced tetrahedron provides a practical strategy for clinical diagnosis and therapy, particularly for aging and age-related diseases.

10.
J Mater Chem B ; 8(9): 1935-1943, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32065194

RESUMO

A monoclonal antibody (mAb) against vitamin B1 was prepared and based on this, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold-based immunochromatographic test (ICT) strip were developed. The 50% inhibition concentration (IC50) and the limit of detection (LOD) for the developed ic-ELISA were estimated to be 20.71 ng mL-1 and 4.51 ng mL-1 in the assay buffer. Vitamin B1 in energy drinks, vitamin tablets, and infant milk powder samples was detected by the developed ic-ELISA and the average recoveries ranged from 80.63% to 103.05%. The vitamin B1 content in energy drinks, vitamin tablets, and infant milk powder samples were confirmed by using liquid chromatography tandem mass spectrometry (LC-MS/MS). Moreover, the cut-off value of the developed ICT strip assay was 250 ng mL-1, with a LOD value of 5.33 ng mL-1. Real samples were used to validate the reliability of the developed ICT strip. All results demonstrated that our developed methods are suitable for the detection of vitamin B1 in food and pharmaceutical products.

11.
J Neurosci ; 40(14): 2849-2858, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32075900

RESUMO

Cortical projections to the thalamus arise from corticothalamic (CT) neurons in layer 6 and pyramidal tract-type (PT) neurons in layer 5B. We dissected the excitatory synaptic connections in the somatosensory thalamus formed by CT and PT neurons of the primary somatosensory (S1) cortex, focusing on mouse forelimb S1. Mice of both sexes were studied. The CT neurons in S1 synaptically excited S1-projecting thalamocortical (TC) neurons in subregions of both the ventral posterior lateral and posterior (PO) nuclei, forming a pair of recurrent cortico-thalamo-cortical (C-T-C) loops. The PT neurons in S1 also formed a recurrent loop with S1-projecting TC neurons in the same subregion of the PO. The PT neurons in the adjacent primary motor (M1) cortex formed a separate recurrent loop with M1-projecting TC neurons in a nearby subregion of the PO. Collectively, our results reveal that C-T-C circuits of mouse forelimb S1 are primarily organized as multiple cortical cell-type-specific and thalamic subnucleus-specific recurrent loops, with both CT and PT neurons providing the strongest excitatory input to TC neurons that project back to S1. The findings, together with those of related studies of C-T-C circuits, thus suggest that recurrently projecting thalamocortical neurons are the principal targets of cortical excitatory input to the mouse somatosensory and motor thalamus.SIGNIFICANCE STATEMENT Bidirectional cortical communication with the thalamus is considered an important aspect of sensorimotor integration for active touch in the somatosensory system, but the cellular organization of the circuits mediating this process is not well understood. We used an approach combining cell-type-specific anterograde optogenetic excitation with single-cell recordings targeted to retrogradely labeled thalamocortical neurons to dissect these circuits. The findings reveal a consistent pattern: cortical projections to the somatosensory thalamus target thalamocortical neurons that project back to the same cortical area. Commonalities of these findings to previous descriptions of related circuits in other areas suggest that cortico-thalamo-cortical circuits may generally be organized primarily as recurrent loops.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31968579

RESUMO

We aimed to assess the risk of oral cancer incidence in a high-risk population, establish a predictive model for oral cancer among these high-risk individuals, and assess the predictive ability of the constructed model. Individuals aged ≥30 years who had a habit of smoking or betel nut chewing and had undergone oral cancer screening in 2010 or 2011 were selected as study subjects. The incidence of oral cancer among the subjects at the end of 2014 was determined. The annual oral cancer incidence among individuals with a positive screening result was 624 per 100,000 persons, which was 6.5 times that of the annual oral cancer incidence among all individuals screened. Male sex, aged 45-64 years, divorce, low educational level, presence of diabetes, presence of other cancers, high comorbidity severity, a habit of smoking or betel nut chewing, and low monthly salary were high-risk factors for oral cancer incidence (p < 0.05). The area under the curve of the predictive model for oral cancer incidence was 0.73, which indicated a good predictive ability. Therefore, the oral cancer screening policy for the high-risk population with a habit of smoking and/or betel nut chewing is beneficial for the early diagnosis of oral cancer.

13.
Food Chem ; 312: 126116, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901821

RESUMO

In this study, we produced a sensitive and specific monoclonal antibody (mAb) against diclazuril based on a new hapten. The mAb, which belongs to the IgG2 subclass, had a 50%-inhibitory concentration of 0.36 ng/mL. A cross reactivity test revealed that the mAb had good specificity for diclazuril. A gold nanoparticle-based lateral-flow strip was assembled for the rapid screening of diclazuril in raw chicken breast and thigh samples. The strip assay had a visual limit of detection (LOD) of 2 µg/kg and a cut-off value of 20 µg/kg for diclazuril in chicken samples when evaluated with the naked eye. With the aid of a strip scan reader, the proposed assay obtained a quantitative measurement for diclazuril with an LOD of 1.08 µg/kg. Therefore, this gold nanoparticle-based lateral-flow strip assay represents a potentially useful tool for on-site detection and rapid initial screening of diclazuril in chicken samples.


Assuntos
Nanopartículas Metálicas , Nitrilos/análise , Triazinas/análise , Animais , Anticorpos Monoclonais/imunologia , Galinhas , Ouro , Limite de Detecção , Fatores de Tempo
14.
Food Chem ; 311: 125897, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31771914

RESUMO

Paraquat (PQ) poisoning is a serious threat to human health that leads to pulmonary toxicity, neurotoxicity, and inflammation. Protecting humans from PQ exposure requires the development of rapid analytical methods for on-site detection. Here, two monoclonal antibodies against PQ were generated and an immunochromatographic assay (ICA) was exploited to determine PQ concentrations in water samples. The results showed that the monoclonal antibody 1D6 exhibited higher affinity and sensitivity, with an affinity constant of 5.4 × 108 mol/L and a limit of detection as low as 0.02 ng/mL. Without sample pretreatment, the developed ICA method provided visible limits of detection ranging from 0.25 to 1 ng/mL, and cut-off limits ranging from 1 to 5 ng/mL, where average recoveries were between 83.15% ± 1.9% and 94.49% ± 2.45% with a coefficient of variation ranging from 1.40% to 7.37%. Importantly, these observations were consistent with liquid chromatography tandem mass spectrometry. These data and results suggested that the ICA method was a reliable, portable, and high-throughput method for determining PQ residues in water samples.

15.
ACS Nano ; 14(1): 28-117, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31478375

RESUMO

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.

16.
Biotechnol J ; 15(1): e1900224, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31468688

RESUMO

Spiramycin (SP) residues in food do harm to human health. It is necessary to establish rapid detection method for SP. In this work, a monoclonal antibody (mAb)-based gold immunochromatography assay (GICA) is developed for the rapid detection of SP. Under optimum conditions, the half-maximal inhibitory concentration of SP-mAb is 0.43 ng mL-1 . The subtype of SP-mAb is IgG2b. This antibody has no cross-reactivity with other analogues and has high affinity (4.52 × 1010 L mol-1 ). Qualitative results can be visualized with the naked eye, with a visual detection limit of 1.0 ng mL-1 and cut-off value of 10 ng mL-1 . A hand-held strip scanner is used for the quantitative analysis, with LOD 0.43 ng mL-1 in assay buffer. The recoveries of SP ranged from 72.3% to 112% in milk and 98.5% to 115% in beef, with variable coefficient ranging from 9.4% to 11.7% in milk and 8.14% to 15.4% in beef. Besides, the proposed GICA method for SP is confirmed by LC-MS/MS in SP-spiked milk and beef samples. Overall, the developed GICA can be a useful tool for SP residues on-site screening in milk and beef samples.

17.
Biotechnol J ; 15(1): e1900174, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31468703

RESUMO

Lincosamides (LMs), include clindamycin (CLIN), lincomycin (LIN), and pirlimycin (PIR), that are widely used as veterinary drugs. LM residues in edible animal origin foods endanger human health and are in urgent need of establishing fast, simple, and highly sensitive detection methods. A gold immunochromatographic strip is prepared to detect CLIN, LIN, and PIR residues simultaneously with a single monoclonal antibody. This antibody is obtained with the design of a novel Hapten and can simultaneously recognize CLIN, LIN, and PIR. Under optimized conditions, the strip results can be semi-quantitatively evaluated with the naked eye within 15 min, with cut-off values in phosphate-buffered saline of 1 ng mL-1 for CLIN, 10 ng mL-1 for LIN, and 25 ng mL-1 for PIR, respectively. Besides, the strip can also be quantified using a hand-held strip scanner, and the spiked samples are used for establishing matrix curves. The limits of detection for CLIN, LIN, and PIR in spiked milk, egg, beef, and honey samples can satisfy the detection requirement. The utility of this strip is also confirmed by positive honey sample. In short, this strip should be expected to be a useful tool for the rapid on-site screening of lincosamide residues in milk, egg, beef, and honey samples.

18.
J Food Sci ; 85(1): 105-113, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31880328

RESUMO

Cyclopiazonic acid (CPA) is an indole-tetramine mycotoxin commonly produced by Penicillium and Aspergillus and is widely found in agricultural products, fermented food, and feed. Food contaminated with CPA poses a substantial health risk to consumers. Therefore, eco-friendly immunoassays, including an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and a lateral flow immunochromatographic strip (LFICS), were developed to monitor CPA in maize and rice samples. For this purpose, a monoclonal antibody (3H12) posed highly resistant to pH (5.6 to 9.6) and ethanol (≤50%) was generated by mouse immunization. Negative maize and rice samples or samples spiked with CPA were extracted with ethanol/0.01 M sodium borate buffer (4/1, v/v, pH 8.4). For ic-ELISA analysis, the limits of detection (LODs) were 0.48 and 0.28 ng/g for maize and rice samples, respectively. The recovery for spiked maize was 76.9% to 83.5% with the highest variable coefficient (CVmax ) being 9.32%. For spiked rice, the recovery was 85.3% to 105.1% with a CVmax of 8.56%. For LFICS analysis, the visible LODs were 2.5 and 1 ng/g and cutoff values were 5 and 2.5 ng/g for maize and rice samples, respectively. The LFICS method gave results within 5 to 10 min, providing an auxiliary analytical tool for the rapid, sensitive, and portable screening of the massive samples onsite.

19.
Small ; 16(3): e1905734, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31851415

RESUMO

Chiral plasmonic nanoassemblies, which exhibit outstanding chiroptical activity in the visible or near-infrared region, are popular candidates in molecular sensing, polarized nanophotonics, and biomedical applications. Their optical chirality can be modulated by manipulating chemical molecule stimuli or replacing the building blocks. However, instead of irreversible chemical or material changes, real-time control of optical activity is desired for reversible and noninvasive physical regulating methods, which is a challenging research field. Here, the directionally and reversibly switching optical chirality of magneto-plasmonic nanoassemblies is demonstrated by the application of an external magnetic field. The gold-magnetic nanoparticles core-satellite (Au@Fe3 O4 ) nanostructures exhibit chiral activity in the UV-visible range, and the circular dichroism signal is 12 times greater under the magnetic field. Significantly, the chiral signal can be reversed by regulating the direction of the applied magnetic field. The attained magnetic field-regulated chirality is attributed to the large contributions of the magnetic dipole moments to polarization rotation. This magnetic field-modulated optical activity may be pivotal for photonic devices, information communication, as well as chiral metamaterials.

20.
Anal Chem ; 92(2): 2310-2315, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31875387

RESUMO

In the present study, a tetrahedron probe with encoded internal reference nanoparticles (NPs) was self-assembled by a complementary nucleic acid aptamer for simultaneous ratiometric detection of telomerase (TE) and epithelial cell-adhesion molecule (EpCAM) in living cells. In the presence of a target, the dissociation of gold (Au) NPs, which was modified with corresponding tags, resulted in decreased surface-enhanced Raman scattering (SERS) signals. In addition, the ratios of Raman intensity at 1346 cm-1/1096 cm-1 (TE) and 1614 cm-1/1096 cm-1 (EpCAM) compared with the internal reference were demonstrated to quantify the level of TE and EpCAM, respectively, and can eliminate certain background noise. A good linear relationship was observed between them, and the linear range of TE and EpCAM in HeLa cells was 0.7 × 10-12 to 37.5 × 10-12 IU and 1.24 to 75.48 pg/mL with a limit of detection (LOD) of 7.6 × 10-16 IU and 0.53 pg/mL, respectively, which were consistent with the results of Raman confocal imaging. Meanwhile, the versatility and specificity of the developed probes were confirmed in cell lines. These results provide a reliable and ultrasensitive strategy for the in situ detection of biomarkers and a new method for SERS-based tetrahedrons in the early diagnosis of cancer.

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