Multihierarchical Regulation To Achieve Quantum Dot Nanospheres with a Photoluminescence Quantum Yield Close to 100.

Quantum dots (QDs) exhibit superior brightness and photochemical stability, making them the preferred option for highly sensitive single-molecule detection compared with fluorescent dyes or proteins. Nevertheless, their high surface energy leads to nonspecific adsorption and poor colloidal stability. In the past decades, we have found that QD-based fluorescent nanoparticles (FNs) can not only address these limitations but also enhance detection sensitivity. However, the photoluminescence quantum yield (PLQY) of FNs is significantly lower compared with that of original QDs. It is urgent to develop a strategy to solve the issue, aiming to further enhance detection sensitivity. In this study, we found that the decrease of PLQY of FNs prepared by free radical polymerization was attributed to two factors: (1) generation of defects that can cause nonradiative transitions resulting from QD-ligands desorption and QD-shell oxidation induced by free radicals; (2) self-absorption resulting from aggregation caused by incompatibility of QDs with polymers. Based on these, we proposed a multihierarchical regulation strategy that includes: (1) regulating QD-ligands; (2) precisely controlling free radical concentration; and (3) constructing cross-linked structures of polymer to improve compatibility and to reduce the formation of surface defects. It is crucial to emphasize that the simultaneous coordination of multiple factors is essential. Consequently, a world-record PLQY of 97.6% for FNs was achieved, breaking through the current bottleneck at 65%. The flexible application of this regulatory concept paves the way for the large-scale production of high-brightness QD-polymer complexes, enhancing their potential applications in sensitive biomedical detection.

Characterization of sciatic nerve myelin sheath during development in C57BL/6 mice.

Myelin sheath plays important roles in information conduction and nerve injury repair in the peripheral nerve system (PNS). Enhancing comprehension of the structure and components of the myelin sheath in the PNS during development would contribute to a more comprehensive understanding of the developmental and regenerative processes. In this research, the structure of sciatic nerve myelin sheath in C57BL/6 mice from embryonic day 14 (E14) to postnatal 12 months (12M) was observed with transmission electron microscopy. Myelin structure appeared in the sciatic nerve as early as E14, and the number and thickness of myelin lamellar gradually increased with the development until 12M. Transcriptome analysis was performed to show the expressions of myelin-associated genes and transcriptional factors involved in myelin formation. The genes encoding myelin proteins (Mag, Pmp22, Mpz, Mbp, Cnp and Prx) showed the same expression pattern, peaking at postnatal day 7 (P7) and P28 after birth, whereas the negative regulators of myelination (c-Jun, Tgfb1, Tnc, Cyr61, Ngf, Egr1, Hgf and Bcl11a) showed an opposite expression pattern. In addition, the expression of myelin-associated proteins and transcriptional factors was measured by Western blot and immunofluorescence staining. The protein expressions of MAG, PMP22, MPZ, CNPase and PRX increased from E20 to P14. The key transcriptional factor c-Jun co-localized with the Schwann cells Marker S100ß and decreased after birth, whereas Krox20/Egr2 increased during development. Our data characterized the structure and components of myelin sheath during the early developmental stages, providing insights for further understanding of PNS development.

Stability Strategies and Applications of Iodide Perovskites.

Iodide perovskites have demonstrated their unprecedented high efficiency and commercialization potential, and their superior optoelectronic properties, such as high absorption coefficient, high carrier mobility, and narrow direct bandgap, have attracted much attention, especially in solar cells, photodetectors, and light-emitting diodes (LEDs). However, whether it is organic iodide perovskite, organic-inorganic hybrid iodide perovskite or all-inorganic iodide perovskite the stability of these iodide perovskites is still poor and the contamination is high. In recent years, scholars have studied more iodide perovskites to improve their stability as well as optoelectronic properties from various angles. This paper systematically reviews the strategies (component engineering, additive engineering, dimensionality reduction engineering, and phase mixing engineering) used to improve the stability of iodide perovskites and their applications in recent years.

Circular photonic crystal grating design for charge-tunable quantum light sources in the telecom C-band.

Efficient generation of entangled photon pairs at telecom wavelengths is a key ingredient for long-range quantum networks. While embedding semiconductor quantum dots into hybrid circular Bragg gratings has proven effective, it conflicts with p-i-n diode heterostructures which offer superior coherence. We propose and analyze hybrid circular photonic crystal gratings, incorporating air holes to facilitate charge carrier transport without compromising optical properties. Through numerical simulations, a broad cavity mode with a Purcell factor of 23 enhancing both exciton and biexciton transitions, and exceptional collection efficiency of 92.4% into an objective with numerical aperture of 0.7 are achieved. Furthermore, our design demonstrates direct coupling efficiency over 90.5% into a single-mode fiber over the entire telecom C-band. The hybrid circular photonic crystal grating thereby emerges as a promising solution for the efficient generation of highly coherent, polarization-entangled photon pairs.

Intracavity spatially modulated metasurfaces for a wavelength-tunable figure-9 vortex fiber laser.

Intracavity optical metasurfaces with compact and flexible light manipulation capabilities, effectively enrich the implementation of miniaturized and user-friendly orbital angular momentum (OAM) laser sources. Here we demonstrate a wavelength-tunable figure-9 Yb-doped vortex fiber laser solely with standard non-polarization-maintaining single-mode fibers, which utilizes a gap-surface plasmon (GSP) metasurface as the intracavity mode regulation component to generate OAM beams, extending the avenues and related applications for cost-effective OAM laser sources. Gained by the broadband operation range of the metasurface, the figure-9 fiber laser could emit OAM light with center wavelength tunable from 1020 nm to 1060 nm and of high mode purity (about 90%). OAM beams with different topological charges such as l = ±1 have been obtained by changing the metasurface design. The proposed fiber laser with the intracavity GSP metasurface provides a reliable and customized output of OAM beams at the laser source, holding great promise for a wide range of applications in optical communications, sensing, and super-resolution imaging.

Single cell analysis reveals the roles and regulatory mechanisms of type-I interferons in Parkinson's disease.

The pathogenesis of Parkinson's disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-ß levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Effects of Semaphorin3A on the growth of sensory and motor neurons.

After peripheral nerve injury, motor and sensory axons can regenerate, but the inaccurate reinnervation of the target leads to poor functional recovery. Schwann cells (SCs) express sensory and motor phenotypes associated with selective regeneration. Semaphorin 3A (Sema3A) is an axonal chemorepellent that plays an essential role in axon growth. SCs can secret Sema3A, and Sema3A presents a different expression pattern at the proximal and distal ends of injured sensory and motor nerves. Hence, in our study, the protein expression and secretion of Sema3A in sensory and motor SCs and the expression of its receptor Neuropilin-1 (Nrp1) in dorsal root ganglia (DRG) sensory neurons (SNs) and spinal cord motor neurons (MNs) were detected by Western blot and ELISA. The effect of Sema3A at different concentrations on neurite growth of sensory and motor neurons was observed by immunostaining. Also, by blocking the Nrp1 receptor on neurons, the effect of Sema3A on neurite growth was observed. Finally, we observed the neurite growth of sensory and motor neurons cocultured with Sema3A siRNA transfected SCs by immunostaining. The results suggested that the expression and secretion of Sema3A in sensory SCs are more significant than that in motor SCs, and the expression of its receptor Nrp1 in SNs is higher than in MNs. Sema3A could inhibit the neurite growth of sensory and motor neurons via Nrp1, and Sema3A has a more substantial effect on the neurite growth of SNs. These data provide evidence that SC-secreted Sema3A might play a role in selective regeneration by a preferential effect on SNs.

Single-Stranded RNA Origami-Based Epigenetic Immunomodulation.

The integration of functional modules at the molecular level into RNA nanostructures holds great potential for expanding their applications. However, the quantitative integration of nucleoside analogue molecules into RNA nanostructures and their impact on the structure and function of RNA nanostructures remain largely unexplored. Here, we report a transcription-based approach to controllably integrate multiple nucleoside analogues into a 2000 nucleotide (nt) single-stranded RNA (ssRNA) origami nanostructure. The resulting integrated ssRNA origami preserves the morphology and biostability of the original ssRNA origami. Moreover, the integration of nucleoside analogues introduced new biomedical functions to ssRNA origamis, including innate immune recognition and regulation after the precise integration of epigenetic nucleoside analogues and synergistic effects on tumor cell killing after integration of therapeutic nucleoside analogues. This study provides a promising approach for the quantitative integration of functional nucleoside analogues into RNA nanostructures at the molecular level, thereby offering valuable insights for the development of multifunctional ssRNA origamis.

A Solid-State Source of Single and Entangled Photons at Diamond SiV-Center Transitions Operating at 80K.

Large-scale quantum networks require the implementation of long-lived quantum memories as stationary nodes interacting with qubits of light. Epitaxially grown quantum dots hold great potential for the on-demand generation of single and entangled photons with high purity and indistinguishability. Coupling these emitters to memories with long coherence times enables the development of hybrid nanophotonic devices that incorporate the advantages of both systems. Here we report the first GaAs/AlGaAs quantum dots grown by the droplet etching and nanohole infilling method, emitting single photons with a narrow wavelength distribution (736.2 ± 1.7 nm) close to the zero-phonon line of silicon-vacancy centers. Polarization entangled photons are generated via the biexciton-exciton cascade with a fidelity of (0.73 ± 0.09). High single photon purity is maintained from 4 K (g(2)(0) = 0.07 ± 0.02) up to 80 K (g(2)(0) = 0.11 ± 0.01), therefore making this hybrid system technologically attractive for real-world quantum photonic applications.

A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620).

BACKGROUND: Veliparib is a poly-ADP-ribose polymerase (PARP) inhibitor, and it has clinical activity with every 3 weeks carboplatin and paclitaxel. In breast cancer, weekly paclitaxel is associated with improved overall survival. We aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib with weekly carboplatin and paclitaxel as well as safety, pharmacokinetics, and preliminary clinical activity in triple negative breast cancer (TNBC). METHODS: Patients with locally advanced/metastatic solid tumors and adequate organ function were eligible. A standard 3 + 3 dose-escalation design was followed by a TNBC expansion cohort. Veliparib doses ranging from 50 to 200 mg orally bid were tested with carboplatin (AUC 2) and paclitaxel (80 mg/m2) given weekly in a 21-day cycle. Adverse events (AE) were evaluated by CTCAE v4.0, and objective response rate (ORR) was determined by RECIST 1.1. RESULTS: Thirty patients were enrolled, of whom 22 had TNBC. Two dose-limiting toxicities were observed. The RP2D was determined to be 150 mg PO bid veliparib with weekly carboplatin and paclitaxel 2 weeks on, 1 week off, based on hematologic toxicity requiring dose reduction in the first 5 cycles of treatment. The most common grade 3/4 AEs included neutropenia, anemia, and thrombocytopenia. PK parameters of veliparib were comparable to single-agent veliparib. In 23 patients with evaluable disease, the ORR was 65%. In 19 patients with TNBC with evaluable disease, the ORR was 63%. CONCLUSION: Veliparib can be safely combined with weekly paclitaxel and carboplatin, and this triplet combination has promising clinical activity.

Immunomodulation with Nucleic Acid Nanodevices.

The precise regulation of interactions of specific immunological components is crucial for controllable immunomodulation, yet it remains a great challenge. With the assistance of advanced computer design, programmable nucleic acid nanotechnology enables the customization of synthetic nucleic acid nanodevices with unprecedented geometrical and functional precision, which have shown promising potential for precise immunoengineering. Notably, the inherently immunologic functions of nucleic acids endow these nucleic acid-based assemblies with innate advantages in immunomodulatory engagement. In this review, the roles of nucleic acids in innate immunity are discussed, focusing on the definition, immunologic modularity, and enhanced bioavailability of structural nucleic acid nanodevices. In light of this, molecular programming and precise organization of functional modules with nucleic acid nanodevices for immunomodulation are emphatically reviewed. At last, the present challenges and future perspectives of nucleic acid nanodevices for immunomodulation are discussed.

Simulation and an experimental study on the optical performance of a Wolter-I focusing mirror based on a 3D ray tracing algorithm.

The nested Wolter-I type focusing mirror is widely used in the field of X-ray astronomy. The thin-shell mirrors produced by the electroforming replication method will introduce various shape errors during the fabricating and assembling process. This study introduces a non-analytical 3D geometrical ray tracing algorithm capable of predicting optical performance for large mirror deformations. The algorithm's implementation involves error reconstruction, light source and ray simulation, and optical performance calculation. Experimental and simulation validation underscores the algorithm's precision and effectiveness. The results also indicate that edge deformation can seriously affect imaging contrast which is generally considered to be determined only by surface scattering. Applying the 3D ray tracing algorithm, a range of low-frequency fabrication and assembly errors are simulated, such as absolute radius, taper, roundness, edge effects, mirror posture, and hoisting deformation errors, and their effects on imaging quality are analyzed and discussed.

Dynamic dual-functional optical wave plate based on phase-change meta-molecules.

Optical metasurfaces have shown great potential for revolutionizing wave plates by enabling compact footprints and diversified functionalities. However, most metasurface wave plates (meta-WPs) are typically passive, featuring defined responses after fabrication, whereas dynamic meta-WPs have so far often been limited to ON and OFF states. Here, we design a dynamic dual-functional meta-WP based on judiciously designed low-loss Sb2Se3 meta-molecules at the telecom wavelength of 1.55 µm which enables reconfigurable linear-to-circular and linear-to-linear polarization conversion for orthogonal linear polarizations when Sb2Se3 transits between amorphous and crystalline states. In addition, a comprehensive electro-thermal simulation is carried out to verify the phase change process for realistic implementation. The designed dynamic dual-functional wave plate may open new avenues for developing integrated adaptive photonics with dynamic and multiplexed functionalities.

Silver nanoparticle-induced enhancement of light extraction in two-dimensional light-emitting diodes.

Monolayer transition metal dichalcogenides (TMDCs) with direct bandgaps are considered promising candidates for building light-emitting diodes (LEDs). One crucial indicator of their performance is the brightness of electroluminescence (EL). In this study, we fabricate WS2-based LEDs that make full use of the assistance of effective transient-mode charge injection. By introducing self-assembled silver nanoparticles (NPs) on top of the LED, the extraction efficiency is significantly improved, with a 2.9-fold EL enhancement observed in the experiment. Full-wave simulations further confirm that the improvement comes from the scattering capability of silver NPs, with results qualitatively fitting the experiment. This approach, with its compatibility with van der Waals heterostructures, can be further promoted to enhance the brightness of 2D monolayer TMDC-based LEDs.

Dissecting the Enantioselective Neurotoxicity of Isocarbophos: Chiral Insight from Cellular, Molecular, and Computational Investigations.

Chiral organophosphorus pollutants are found abundantly in the environment, but the neurotoxicity risks of these asymmetric chemicals to human health have not been fully assessed. Using cellular, molecular, and computational toxicology methods, this story is to explore the static and dynamic toxic actions and its stereoselective differences of chiral isocarbophos toward SH-SY5Y nerve cells mediated by acetylcholinesterase (AChE) and further dissect the microscopic basis of enantioselective neurotoxicity. Cell-based assays indicate that chiral isocarbophos exhibits strong enantioselectivity in the inhibition of the survival rates of SH-SY5Y cells and the intracellular AChE activity, and the cytotoxicity of (S)-isocarbophos is significantly greater than that of (R)-isocarbophos. The inhibitory effects of isocarbophos enantiomers on the intracellular AChE activity are dose-dependent, and the half-maximal inhibitory concentrations (IC50) of (R)-/(S)-isocarbophos are 6.179/1.753 µM, respectively. Molecular experiments explain the results of cellular assays, namely, the stereoselective toxic actions of isocarbophos enantiomers on SH-SY5Y cells are stemmed from the differences in bioaffinities between isocarbophos enantiomers and neuronal AChE. In the meantime, the modes of neurotoxic actions display that the key amino acid residues formed strong noncovalent interactions are obviously different, which are related closely to the molecular structural rigidity of chiral isocarbophos and the conformational dynamics and flexibility of the substrate binding domain in neuronal AChE. Still, we observed that the stable "sandwich-type π-π stacking" fashioned between isocarbophos enantiomers and aromatic Trp-86 and Tyr-337 residues is crucial, which notably reduces the van der Waals' contribution (ΔGvdW) in the AChE-(S)-isocarbophos complexes and induces the disparities in free energies during the enantioselective neurotoxic conjugations and thus elucidating that (S)-isocarbophos mediated by synaptic AChE has a strong toxic effect on SH-SY5Y neuronal cells. Clearly, this effort can provide experimental insights for evaluating the neurotoxicity risks of human exposure to chiral organophosphates from macroscopic to microscopic levels.

The plasma levels of Dickkopf-1 elevated in patients with Juvenile Idiopathic Arthritis.

BACKGROUND: To explore the role of two major inhibitors of Wnt signal pathway, Dickkopf-1(DKK-1) and Sclerostin (SOST), in the pathogenesis of juvenile idiopathic arthritis (JIA). METHODS: 88 patients with JIA, which including 49 patients with enthesitis-related arthritis (ERA), 21 oligoarthritis (oJIA) and 18 polyarthritis (pJIA), and 36 age-and sex-matched children as healthy controls (HC) were enrolled in this study. The plasma levels of DKK-1 and SOST, measured using commercially available ELISA kits, were analyzed the correlation between the levels of DKK-1/SOST and JIA, and were analyzed in 14 patients with JIA during before and after treatment. RESULTS: Plasma levels of DKK-1 were significantly higher in the patients with JIA than that in HC, the elevation of DKK-1 level was positively correlated with HLA-B27 positive JIA. DKK-1 levels dropped significantly in patient with JIA after treatment (P < 0.05). There was no significant change in SOST levels among different subtypes of JIA, patients with JIA during before and after treatment, and HC. CONCLUSION: It was suggested that the DKK-1 may have a certain correlation with the pathogenesis of JIA, and DKK-1 levels are more closely related to the HLA-B27 positive-ERA. IMPACT: The abnormally elevated levels of Dickkopf-1 (DKK-1) may be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). DKK-1 levels were more closely related to the HLA-B27 positive-enthesitis-related arthritis (ERA). DKK-1 is an inhibitor of Wnt signaling pathway that promotes osteoblastic new bone formation; it is very rare for pediatric patients with HLA-B27 positive-ERA to manifest typical spondylitis, while sacroiliac arthritis is relatively common, which may be related to the high levels of DKK-1, which is consistent with the early stage of ankylosing spondylitis (AS).

Semaphorin 3E promote Schwann cell proliferation and migration.

Schwann cells (SCs) play a critical role in peripheral nerve (PN) regeneration because of their ability to proliferate, migrate, and provide trophic support for axon regeneration after PN injury. However, the underlying mechanism is still partially understood. Semaphorin3E (Sema3E), a member of the Sema3s family, is a secreted molecular known as a repelling cue in axon guidance and inhibitor of developmental and postischemic angiogenesis. In this study, we examined the expression of Sema3E in sciatic nerves and SCs and explored the effects of Sema3E on SCs proliferation and migration. Immunofluorescence and ELISA analyses illustrated the expression of Sema3E in SCs of Sciatic nerves and the secretion of Sema3E by cultured SCs, respectively. Exogenous Sema3E promoted SC proliferation and migration while knockdown of the endogenous Sema3E by siRNA transfection attenuated proliferation and migration of SCs. Furthermore, blocking the receptor Neuropilin 1 (Nrp1), PlexinD1 and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) by neutralizing antibody or inhibitor suppressed the promoting effects of Sema3E on SCs. This study indicated that Sema3E promoted SC proliferation and migration and the involvement of receptor PlexinD1, Nrp1, and VEGFR2 in these processes. This study extended our understanding of the mechanism that modulated SC phenotype during nerve injury and provided a potential target for promoting PN regeneration.

MEMS Tunable Metasurfaces Based on Gap Plasmon or Fabry-Pérot Resonances.

Tunable metasurfaces promise to enable adaptive optical systems with complex functionalities. Among possible realizations, a recent platform combining microelectromechanical systems (MEMS) with gap-surface plasmon (GSP) metasurfaces offers high modulation efficiency, broadband operation, and fast response. We compare tunable metasurfaces operating in GSP and Fabry-Pérot (FP) regions by investigating polarization-independent blazed gratings both numerically and experimentally. Peak efficiency is calculated to be ∼75% in both cases (∼40% in measurements), while the operation bandwidth is found larger when operating in the GSP region. Advantages of operating in the FP region include relaxed assembly requirements and operation tolerances. Additionally, simulation and experimental results show that coupling between neighboring unit cells increases for larger air gaps, resulting in deteriorated efficiency. We believe the presented analysis provides important guidelines for designing tunable metasurfaces for diverse applications in miniaturized adaptive optical systems.

The acetylome of adult mouse sciatic nerve.

Lysine acetylation is a reversible post-translational modification (PTM) involved in multiple physiological functions. Recent studies have demonstrated the involvement of protein acetylation in modulating the biology of Schwann cells (SCs) and regeneration of the peripheral nervous system (PNS). However, the mechanisms underlying these processes remain partially understood. Here, we characterized the acetylome of the mouse sciatic nerve (SN) and investigated the cellular distribution of acetylated proteins. We identified 483 acetylated proteins containing 1442 acetylation modification sites in the SN of adult C57BL/6 mice. Bioinformatics suggested that these acetylated SN proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and cytoskeleton, and highlighted the significant differences between the mouse SN and brain acetylome. Manual annotation further indicated that most acetylated proteins (> 45%) were associated with mitochondria, energy metabolism, and cytoskeleton and cell adhesion. We verified three newly discovered acetylation-modified proteins, including neurofilament light polypeptide (NEFL), neurofilament medium/high polypeptide (NFM/H), and periaxin (PRX). Immunofluorescence illustrated that the acetylated proteins, including acetylated alpha-tubulin, were mainly co-localized with S100-positive SCs. Herein, we provided a comprehensive acetylome for the mouse SN and demonstrated that acetylated proteins in the SN were predominantly located in SCs. These results will extend our understanding and promote further study of the role and mechanism of protein acetylation in SC development and PNS regeneration.

DNA Zipper Mediated Membrane Fusion for Rapid Exosomal MiRNA Detection.

Accurate and reliable detection of exosomal miRNA can serve as a promising method for early diagnosis of disease and evaluation of therapeutic effects. However, current exosomal miRNA detection methods commonly involve exosome enrichment, containing RNA extraction, and qRT-PCR based quantification, which are expensive and time-consuming. Herein, we develop a DNA zipper-mediated membrane fusion approach for rapid exosomal miRNA detection and cancer diagnosis. First, a lipid vesicle probe containing miR21-targeting molecular beacons (MBs) is constructed and further loaded with zipper DNA constructs (ZDCs) on its surface. Meanwhile, complementary zipper DNA constructs (cZDCs) are introduced on the exosome of interest. Upon mixing them together, zipping between ZDC and cZDC induces the membrane fusion of exosomes and vesicle probes, triggering the recognition of exosomal miR21 by contained MBs and fluorescence emission that can be conveniently detected within 30 min. Importantly, with the assistance of flow cytometry, miR21-overexpressed tumor exosomes derived from either cell culture medium or clinical patient serums can be distinguished from exosomes secreted from normal cells. This approach provides a convenient way to accurately detect the exosomal miRNA, which may hold great potential in liquid biopsy for early cancer diagnosis and monitoring the therapeutic effects during the treatments.