Novel screening test for celiac disease using peptide functionalised gold nanoparticles

AIM To develop a screening test for celiac disease based on the coating of gold nanoparticles with a peptide sequence derived from gliadin, the protein that triggers celiac disease.METHODS20 nm gold nanoparticles were first coated with NeutrAvidin. A long chain Polyethylene glycol(PEG) linker containing Maleimide at the Ω-end and Biotin group at the α-end was used to ensure peptide coating to the gold nanoparticles. The maleimide group with the thiol(-SH) side chain reacted with the cysteine amino acid in the peptide sequence and the biotinylated and PEGylated peptide was added to the NeutrAvidin coated gold nanoparticles. The peptide coated gold nanoparticles were then converted into a serological assay. We used the peptide functionalised gold nanoparticle-based assay on thirty patient serum samples in a blinded assessment and compared our results with the previously run serologicaland pathological tests on these patients.RESULTS A stable colloidal suspension of peptide coated gold nanoparticles was obtained without any aggregation. An absorbance peak shift as well as color change was caused by the aggregation of gold nanoparticles following the addition of anti-gliadin antibody to peptide coated nanoparticles at levels associated with celiac disease. The developed assay has been shown to detect anti-gliadin antibody not only in quantitatively spiked samples but also in a small-scale study on real non-hemolytic celiac disease patient's samples.CONCLUSION The study demonstrates the potential of gold nanoparticlepeptide based approach to be adapted for developing a screening assay for celiac disease diagnosis. The assay could be a part of an exclusion based diagnostic strategy and prove particularly useful for testing high celiac disease risk populations.

Laterally swept light-sheet microscopy enhanced by pixel reassignment for photon-efficient volumetric imaging

In light-sheet fluorescence microscopy,the axial resolution and field of view are mutually constrained.Axially swept light-sheet microscopy(ASLM)can decouple the trade-off,but the confocal detection scheme using a rolling shutter also rejects fluorescence signals from the specimen in the field of interest,which sacrifices the photon efficiency.Here,we report a laterally swept light-sheet microscopy(LSLM)scheme in which the focused beam is first scanned along the axial direction and subsequently laterally swept with the rolling shutter.We show that LSLM can obtain a higher photon efficiency when similar axial resolution and field of view can be achieved.Moreover,based on the principle of image scanning microscopy,applying the pixel reassignment to the LSLM images,hereby named iLSLM,improves the optical sectioning.Both simulation and experimental results demonstrate the higher photon efficiency with similar axial resolution and optical sectioning.Our proposed scheme is suitable for volumetric imaging of specimens that are susceptible to photobleaching or phototoxicity.

Super-resolution fluorescence polarization microscopy

Fluorescence polarization is related to the dipole orientation of chromophores,making fuores-cence polarization microscopy possible to_reveal structures and functions of tagged cellularorganelles and biological macromolecules.Several recent super resolution techniques have beenapplied to fluorescence polarization microscopy,achieving dipole measurement at nanoscale.In this review,we summarize both difraction limited and super resolution fluorescence polari-zation microscopy techniques,as well as their applications in biological imaging.

Entropy-driven strand displacement reaction for ultrasensitive detection of circulating tumor DNA based on upconversion and Fe_(3)O_(4) nanocrystals

Early detection of cancer biomarkers applied in real-time disease diagnosis and therapies can increase the survival rate of patients.Circulating tumor DNA(ct DNA)as a typical cancer biomarker plays a great role in the process of tumor disease monitoring,especially in early diagnosis.Unfortunately,most ct DNA detection systems have not been widely used due to their low sensitivity,poor specificity,and high cost.Herein,we developed an alternative ct DNA detection system to present the levels of ct DNA by recording the fluorescence signals of the system containing upconversion nanoparticles(UCNPs),Fe_(3)O_(4),and entropy-driven strand displacement reaction.The method has a practical sensitivity with a wide linear range from 100 amol L^(-1)to 1 nmol L^(-1)and a low detection limit of 1.6 amol L^(-1).Furthermore,the system demonstrates a practical application in mouse blood serum samples and meets the requirements for rapid,sensitive,specific,and economical diagnosis of cancers.Thus,this ct DNA detection system may have great potential for ct DNAdetection and clinical diagnosis.

Defect and interface control on graphitic carbon nitrides/upconversion nanocrystals for enhanced solar hydrogen production

The effective utilization of solar energy for hydrogen production requires an abundant supply of thermodynamically active photo-electrons;however,the photocatalysts are generally impeded by insufficient light absorption and fast photocarrier recombination.Here,we report a multiple-regulated strategy to capture photons and boost photocarrier dynamics by devel-oping a broadband photocatalyst composed of defect engineered g-C_(3)N_(4)(DCN)and upconversion NaYF4:Yb^(3+),Tm^(3+)(NYF)nanocrystals.Through a precise defect engineering,the S dopants and C vacancies jointly render DCN with defect states to effectively extend the visible light absorption to 590 nm and boost photocarrier separation via a moderate electron-trapping ability,thus facilitating the subsequent re-absorption and utilization of upconverted photons/electrons.Importantly,we found a promoted interfacial charge polarization between DCN and NYF has also been achieved mainly due to Y-N interaction,which further favors the upconverted excited energy transfer from NYF onto DCN as verified both theoretically and experimentally.With a 3D architecture,the NYF@DCN catalyst exhibits a superior solar H2 evolution rate among the reported upconversion-based system,which is 19.3 and 1.5 fold higher than bulk material and DCN,respectively.This work provides an innovative strategy to boost solar utilization by using defect engineering and building up interaction between hetero-materials.

Er_(2)TiO_(5)@Ag nanocomposites:Enhanced photocatalysis and bacteria inactivation,and cytotoxicity

In this study,we successfully synthesized Er_(2)TiO_(5)@Ag nanocomposites(NCPs) using the ultrasonicmediated sol-gel technique to create a multifunctional material with enhanced photocatalytic and antibacterial properties.The visible light photocatalytic activities of Er_(2)TiO_(5) nanoparticles(NPs) and Er_(2)TiO_(5)@Ag NCPs were systematically evaluated under various conditions,including different concentrations of Basic Blue 41(BB 41) dye and photocatalyst.The results reveal a remarkable improvement in the photocatalytic degradation efficiency of Er_(2)TiO_(5)@Ag NCPs(95%) compared to Er_(2)TiO_(5) NPs(80%).Furthermore,the antibacterial efficacy of Er_(2)TiO_(5) NPs and Er2TiO_5@Ag NCPs were extensively examined against Gram-positive and Gram-negative bacteria.Notably,Er_(2)TiO_(5)@Ag NCPs exhibit significantly higher minimum bactericidal concentration(MBC) values compared to Er_(2)TiO_(5) NPs.The antibacterial effect of Er_(2)TiO_(5)@Ag NCPs is particularly pronounced against S.aureus and Pseudomonas aeruginosa,while demonstrating moderate effects on Escherichia coli and Enterococcus faecalis.To assess the biocompatibility of the synthesized materials,we investigated their internalization by MCF-7 cells.Encouragingly,both Er_(2)TiO_(5) NPs and Er_(2)TiO_(5)@Ag NCPs are found to be effectively internalized by the cells,suggesting their potential application in biomedical fields.Intriguingly,our study unveils the exceptional potential of Er_(2)TiO_(5)@Ag NCPs as a dual-action solution,simultaneously possessing enhanced photocatalytic efficiency and potent antibacterial properties.This multifunctional nanocomposite not only outperforms Er_(2)TiO_(5) and Ag but also paves the way for innovative applications in sustainable environmental remediation and advanced biomedical technologies,promising a brighter and cleaner future.

NIR regeneration and visible luminescence modification in photochromic glass:A novel encryption and 3D optical storage medium

Photochromic glass shows great promise for 3D optical information encryption and storage applications.The formation of Ag nanoclusters by light irradiation has been a significant development in the field of photochromic glass research.However,extending this approach to other metal nanoclusters remains a challenge.In this study,we present a pioneering method for crafting photochromic glass with reliably adjustable dual-mode luminescence in both the NIR and visible spectra.This was achieved by leveraging bimetallic clusters of bismuth,resulting in a distinct and novel photochromic glass.When rare-earth-doped,bismuth-based glass is irradiated with a 473 nm laser,and it undergoes a color transformation from yellow to red,accompanied by visible and broad NIR luminescence.This phenomenon is attributed to the formation of laserinduced(Bi^(+),Bi^(0))nanoclusters.We achieved reversible manipulation of the NIR luminescence of these nanoclusters and visible rare-earth luminescence by alternating exposure to a 473 nm laser and thermal stimulation.Information patterns can be inscribed and erased on a glass surface or in 3D space,and the readout is enabled by modulating visible and NIR luminescence.This study introduces a pioneering strategy for designing photochromic glasses with extensive NIR luminescence and significant potential for applications in highcapacity information encryption,optical data storage,optical communication,and NIR imaging.The exploration of bimetallic cluster formation in Bi represents a vital contribution to the advancement of multifunctional glass systems with augmented optical functionalities and versatile applications.

Bacterial nanotechnology as a paradigm in targeted cancer therapeutic delivery and immunotherapy

Cancer,a multifaceted and diverse ailment,presents formidable obstacles to traditional treatment modalities.Nanotechnology presents novel prospects for surmounting these challenges through its capacity to facilitate meticulous and regulated administration of therapeutic agents to malignant cells while concurrently modulating the immune system to combat neoplasms.Bacteria and their derivatives have emerged as highly versatile and multifunctional platforms for cancer nanotherapy within the realm of nanomaterials.This comprehensive review delves into the multifaceted and groundbreaking implementations of bacterial nanotechnology within cancer therapy.This review encompasses four primary facets:the utilization of bacteria as living conveyors of medicinal substances,the employment of bacterial components as agents that stimulate the immune system,the deployment of bacterial vectors as tools for delivering genetic material,and the development of bacteria-derived nano-drugs as intelligent nano-medications.Furthermore,we elucidate the merits and modalities of operation pertaining to these bacterial nano-systems,along with their capacity to synergize with other cutting-edge nanotechnologies,such as CRISPR-Cas systems.Additionally,we offer insightful viewpoints regarding the forthcoming trajectories and prospects within this expanding domain.It is our deduction that bacterial nanotechnology embodies a propitious and innovative paradigm in the realm of cancer therapy,which has the potential to provide numerous advantages and synergistic effects in enhancing the outcomes and quality of life for individuals afflicted with cancer.

Microscopic inspection and tracking of single upconversion nanoparticles in living cells

Nanoparticles have become new tools for cell biology imaging1,sub-cellular sensing2,super-resolution imaging3,4 and drug delivery5.Long-term 3D tracking of nanoparticles and their intracellular motions have advanced the understanding of endocytosis and exocytosis as well as of active transport processes6–8.The sophisticated operation of correlative optical-electron microscopy9,10 and scientific-grade cameras is often used to study intercellular processes.Nonetheless,most of these studies are still limited by the insufficient sensitivity for separating a single nanoparticle from a cluster of nanoparticles or their aggregates8,11,12.Here we report that our eyes can track a single fluorescent nanoparticle that emits over 4000 photons per 100 milliseconds under a simple microscope setup.By tracking a single nanoparticle with high temporal,spectral and spatial resolution,we show the measurement of the local viscosity of the intracellular environment.Moreover,beyond the colour domain and 3D position,we introduce excitation power density as the fifth dimension for our eyes to simultaneously discriminate multiple sets of single nanoparticles.

New strategy for designing orangish-redemitting phosphor via oxygen-vacancyinduced electronic localization

Phosphor-converted white-light-emitting diodes(pc-WLED)have been extensively employed as solid-state lighting sources,which have a very important role in people’s daily lives.However,due to the scarcity of the red component,it is difficult to realize warm white light efficiently.Hence,red-emitting phosphors are urgently required for improving the illumination quality.In this work,we develop a novel orangish-red La_(4)GeO_(8):Bi^(3+) phosphor,the emission peak of which is located at 600 nm under near-ultraviolet(n-UV)light excitation.The full width at half maximum(fwhm)is 103 nm,the internal quantum efficiency(IQE)exceeds 88%,and the external quantum efficiency(EQE)is 69%.According to Rietveld refinement analysis and density functional theory(DFT)calculations,Bi^(3+) ions randomly occupy all La sites in orthorhombic La_(4)GeO_(8).Importantly,the oxygen-vacancy-induced electronic localization around the Bi3+ions is the main reason for the highly efficient orangish-red luminescence.These results provide a new perspective and insight from the local electron structure for designing inorganic phosphor materials that realize the unique luminescence performance of Bi^(3+) ions.

Exploring the potential and safety of quantum dots in allergy diagnostics

Biomedical investigations in nanotherapeutics and nanomedicine have recently intensified in pursuit of new therapies with improved efficacy.Quantum dots(QDs)are promising nanomaterials that possess a wide array of advantageous properties,including electronic properties,optical properties,and engineered biocompatibility under physiological conditions.Due to these characteristics,QDs are mainly used for biomedical labeling and theranostic(therapeutic-diagnostic)agents.QDs can be functionalized with ligands to facilitate their interaction with the immune system,specific IgE,and effector cell receptors.However,undesirable side effects such as hypersensitivity and toxicity may occur,requiring further assessment.This review systematically summarizes the potential uses of QDs in the allergy field.An overview of the definition and development of QDs is provided,along with the applications of QDs in allergy studies,including the detection of allergen-specific IgE(sIgE),food allergens,and sIgE in cellular tests.The potential treatment of allergies with QDs is also described,highlighting the toxicity and biocompatibility of these nanodevices.Finally,we discuss the current findings on the immunotoxicity of QDs.Several favorable points regarding the use of QDs for allergy diagnosis and treatment are noted.

Upconversion nanoparticles for super-resolution quantification of single small extracellular vesicles

Although small EVs(sEVs)have been used widely as biomarkers in disease diagnosis,their heterogeneity at single EV level has rarely been revealed.This is because high-resolution characterization of sEV presents a major challenge,as their sizes are below the optical diffraction limit.Here,we report that upconversion nanoparticles(UCNPs)can be used for super-resolution profiling the molecular heterogeneity of sEVs.We show that Er3+-doped UCNPs has better brightness and Tm3+-doped UCNPs resulting in better resolution beyond diffraction limit.Through an orthogonal experimental design,the specific targeting of UCNPs to the tumour epitope on single EV has been cross validated,resulting in the Pearson’s R-value of 0.83 for large EVs and~65%co-localization double-positive spots for sEVs.Furthermore,super-resolution nanoscopy can distinguish adjacent UCNPs on single sEV with a resolution of as high as 41.9 nm.When decreasing the size of UCNPs from 40 to 27 nm and 18 nm,we observed that the maximum UCNPs number on single sEV increased from 3 to 9 and 21,respectively.This work suggests the great potentials of UCNPs approach“digitally”quantify the surface antigens on single EVs,therefore providing a solution to monitor the EV heterogeneity changes along with the tumour progression progress.

Ultra-high spatio-temporal resolution imaging with parallel acquisition-readout structured illumination microscopy(PAR-SIM)

Structured illumination microscopy(SIM)has emerged as a promising super-resolution fluorescence imaging technique,offering diverse configurations and computational strategies to mitigate phototoxicity during real-time imaging of biological specimens.Traditional efforts to enhance system frame rates have concentrated on processing algorithms,like rolling reconstruction or reduced frame reconstruction,or on investments in costly sCMOS cameras with accelerated row readout rates.In this article,we introduce an approach to elevate SIM frame rates and region of interest(ROI)coverage at the hardware level,without necessitating an upsurge in camera expenses or intricate algorithms.Here,parallel acquisition-readout SIM(PAR-SIM)achieves the highest imaging speed for fluorescence imaging at currently available detector sensitivity.By using the full frame-width of the detector through synchronizing the pattern generation and image exposure-readout process,we have achieved a fundamentally stupendous information spatial-temporal flux of 132.9 MPixels·s^(−1),9.6-fold that of the latest techniques,with the lowest SNR of−2.11 dB and 100 nm resolution.PAR-SIM demonstrates its proficiency in successfully reconstructing diverse cellular organelles in dual excitations,even under conditions of low signal due to ultra-short exposure times.Notably,mitochondrial dynamic tubulation and ongoing membrane fusion processes have been captured in live COS-7 cell,recorded with PAR-SIM at an impressive 408 Hz.We posit that this novel parallel exposure-readout mode not only augments SIM pattern modulation for superior frame rates but also holds the potential to benefit other complex imaging systems with a strategic controlling approach.

Three-dimensional breast cancer tumor models based on natural hydrogels:a review

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹ collagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

Super-resolution dipole orientation mapping via polarization demodulation

Fluorescence polarization microscopy(FPM)aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy.Conventional FPM often suffers from the presence of a large number of molecules within the diffraction-limited volume,with averaged fluorescence polarization collected from a group of dipoles with different orientations.Here,we apply sparse deconvolution and least-squares estimation to fluorescence polarization modulation data and demonstrate a super-resolution dipole orientation mapping(SDOM)method that resolves the effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area.We further apply this method to resolve structural details in both fixed and live cells.For the first time,we show that different borders of a dendritic spine neck exhibit a heterogeneous distribution of dipole orientation.Furthermore,we illustrate that the dipole is always perpendicular to the direction of actin filaments in mammalian kidney cells and radially distributed in the hourglass structure of the septin protein under specific labelling.The accuracy of the dipole orientation can be further mapped using the orientation uniform factor,which shows the superiority of SDOM compared with its wide-field counterpart as the number of molecules is decreased within the smaller focal area.Using the inherent feature of the orientation dipole,the SDOM technique,with its fast imaging speed(at sub-second scale),can be applied to a broad range of fluorescently labeled biological systems to simultaneously resolve the valuable dipole orientation information with super-resolution imaging.

Mirror-enhanced super-resolution microscopy

Axial excitation confinement beyond the diffraction limit is crucial to the development of next-generation,super-resolution microscopy.STimulated Emission Depletion(STED)nanoscopy offers lateral super-resolution using a donut-beam depletion,but its axial resolution is still over 500 nm.Total internal reflection fluorescence microscopy is widely used for single-molecule localization,but its ability to detect molecules is limited to within the evanescent field of~100 nm from the cell attachment surface.We find here that the axial thickness of the point spread function(PSF)during confocal excitation can be easily improved to 110 nm by replacing the microscopy slide with a mirror.The interference of the local electromagnetic field confined the confocal PSF to a 110-nm spot axially,which enables axial super-resolution with all laser-scanning microscopes.Axial sectioning can be obtained with wavelength modulation or by controlling the spacer between the mirror and the specimen.With no additional complexity,the mirror-assisted excitation confinement enhanced the axial resolution six-fold and the lateral resolution two-fold for STED,which together achieved 19-nm resolution to resolve the inner rim of a nuclear pore complex and to discriminate the contents of 120 nm viral filaments.The ability to increase the lateral resolution and decrease the thickness of an axial section using mirror-enhanced STED without increasing the laser power is of great importance for imaging biological specimens,which cannot tolerate high laser power.

Emerging role of machine learning in light-matter interaction

Machine learning has provided a huge wave of innovation in multiple fields,including computer vision,medical diagnosis,life sciences,molecular design,and instrumental development.This perspective focuses on the implementation of machine learning in dealing with light-matter interaction,which governs those fields involving materials discovery,optical characterizations,and photonics technologies.We highlight the role of machine learning in accelerating technology development and boosting scientific innovation in the aforementioned aspects.We provide future directions for advanced computing techniques via multidisciplinary efforts that can help to transform optical materials into imaging probes,information carriers and photonics devices.

Polarization modulation with optical lock-in detection reveals universal fluorescence anisotropy of subcellular structures in live cells

The orientation of fluorophores can reveal crucial information about the structure and dynamics of their associated subcellular organelles.Despite significant progress in super-resolution,fluorescence polarization microscopy remains limited to unique samples with relatively strong polarization modulation and not applicable to the weak polarization signals in samples due to the excessive background noise.Here we apply optical lock-in detection to amplify the weak polarization modulation with super-resolution.This novel technique,termed optical lock-in detection super-resolution dipole orientation mapping(OLID-SDOM),could achieve a maximum of 100 frames per second and rapid extraction of 2D orientation,and distinguish distance up to 50 nm,making it suitable for monitoring structural dynamics concerning orientation changes in vivo.OLID-SDOM was employed to explore the universal anisotropy of a large variety of GFP-tagged subcellular organelles,including mitochondria,lysosome,Golgi,endosome,etc.We found that OUF(Orientation Uniformity Factor)of OLID-SDOM can be specific for different subcellular organelles,indicating that the anisotropy was related to the function of the organelles,and OUF can potentially be an indicator to distinguish normal and abnormal cells(even cancer cells).Furthermore,dual-color super-resolution OLID-SDOM imaging of lysosomes and actins demonstrates its potential in studying dynamic molecular interactions.The subtle anisotropy changes of expanding and shrinking dendritic spines in live neurons were observed with real-time OLID-SDOM.Revealing previously unobservable fluorescence anisotropy in various samples and indicating their underlying dynamic molecular structural changes,OLID-SDOM expands the toolkit for live cell research.

A stoichiometric terbium-europium dyad molecular thermometer: energy transfer properties

The optical thermometer has shown great promise for use in the fields of aeronautical engineering,environmental monitoring and medical diagnosis.Self-referencing lanthanide thermo-probes distinguish themselves because of their accuracy,calibration,photostability,and temporal dimension of signal.However,the use of conventional lanthanidedoped materials is limited by their poor reproducibility,random distance between energy transfer pairs and interference by energy migration,thereby restricting their utility.Herein,a strategy for synthesizing hetero-dinuclear complexes that comprise chemically similar lanthanides is introduced in which a pair of thermosensitive dinuclear complexes,cycTb-phEu and cycEu-phTb,were synthesized.Their structures were geometrically optimized with an internuclear distance of approximately 10.6Å.The sensitive linear temperature-dependent luminescent intensity ratios of europium and terbium emission over a wide temperature range(50–298 K and 10–200 K,respectively)and their temporal dimension responses indicate that both dinuclear complexes can act as excellent self-referencing thermometers.The energy transfer from Tb^(3+)to Eu^(3+)is thermally activated,with the most important pathway involving the ^(7)F_(1) Eu^(3+)J-multiplet at room temperature.The energy transfer from the antenna to Eu^(3+)was simulated,and it was found that the most important ligand contributions to the rate come from transfers to the Eu^(3+)upper states rather than direct ligand–metal transfer to 5D1 or 5D0.As the first molecular-based thermometer with clear validation of the metal ratio and a fixed distance between the metal pairs,these dinuclear complexes can be used as new materials for temperature sensing and can provide a new platform for understanding the energy transfer between lanthanide ions.

A homogeneous DNA assay by recovering inhibited emission of rare earth ions-doped upconversion nanoparticles

Robust and easy-to-use kits specific for a particular DNA sequence are desirable for early detection of diseases. However, the major challenge with these tests is often the background fluorescence artifacts arising from biological species due to employing UV and visible range of light. Here, we have reported a near-infrared (NIR) fluorescence "turn-on" kit based on rare earth ions doped nanoparticles, upconversion nanoparticles (UCNPs), and gold nanoparticles (AuNPs), which forms a fluorescence-quencher pair,brought together by a hairpin structure through the formation of double-stranded DNA (dsDNA), with quenched upconversion luminescence. In the presence of analytes, the molecular beacon opens to push AuNPs away from UCNPs, with a distance longer than the efficient quenching distance, so that the inhibited upconversion emission will be restored. We demonstrated that this assay provides a homogeneous, facile, simple and highly selective HIV-1 based DNA detection system with restore efficiency up to 85%, and the detection limit of 5 nm.