Evaluating the hypolipidemic effect of garlic essential oil encapsulated in a novel double-layer delivery system.

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and ß-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO ß-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2023 ASH annual meeting.

Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based therapies specifically tailored for those with R/R AML remains scarce. Here, we provide a comprehensive overview of the latest data presented at the 65th American Society of Hematology Annual Meeting, shedding light on the progress and efficacy of VEN-based therapies for R/R AML.

Rational Design of Guanidinium-Based Bio-MCOF as a Multifunctional Nanocatalyst in Tumor Cells for Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) has emerged as a promising approach to cancer treatment, which can break the intracellular redox state balance and result in severe oxidative damage to biomolecules and organelles with the advantages of being less dependent on external stimulation, having deep tissue-healing abilities, and being resistant to drug resistance. There is considerable interest in developing CDT drugs with high efficiency and low toxicity. In this study, a new guanidinium-based biological metal covalent organic framework (Bio-MCOF), GZHMU-1@Mo, is rationally designed and synthesized as a multifunctional nanocatalyst in tumor cells for enhanced CDT. The DFT calculation and experimental results showed that due to the ability of MoO42- ion to promote electron transfer and increase the redox active site, Cu3 clusters and MoO42- ions in GZHMU-1@Mo can synergistically catalyze the production of reactive oxygen species (ROS) from oxygen and H2O2 in tumor cells, as well as degrade intracellular reducing substances, GSH and NADH, so as to disrupt the redox balance in tumor cells. Moreover, GZHMU-1@Mo exhibits a potent killing effect on tumor cells under both normal oxygen and anaerobic conditions. Further in vitro and in vivo antiproliferation studies revealed that the GZHMU-1@Mo nanoagent displays a remarkable antiproliferation effect and effectively inhibits tumor growth. Taken together, our study provides an insightful reference benchmark for the rational design of Bio-MCOF-based nanoagents with efficient CDT.

Dual-Recognition Triggered Proximity Ligation Combined with a Rolling Circle Amplification Strategy for Analysis of Exosomal Protein-Specific Glycosylation.

Exosomal surface glycan reveals the biological function and molecular information on the protein, especially in indicating the pathogenesis of certain diseases through monitoring of specific protein glycosylation accurately. However, in situ and nondestructive measurement techniques for certain Exosomal glycoproteins are still lacking. In this work, combined with on-chip purification, we designed a proximity ligation assay-induced rolling circle amplification (RCA) strategy for highly sensitive identification of Exosomal protein-specific glycosylation based on a couple of proximity probes to target Exosomal protein and the protein-specific glycosylation site. Benefiting from efficient separation, scalable dual-recognition, and proximity-triggered RCA amplification, the proposed strategy could convert different protein-specific glycan levels to prominent changes in absorbance signals, resulting in accurate quantification of specific glycosylated Exosomal protein. When detecting the glycosylated PD-L1 on MDA-MB-231 exosomes and glycosylated PTK7 on HepG2 exosomes, the detection limits were calculated to be as low as 1.04 × 104 and 2.759 × 103 particles/mL, respectively. In addition, we further expand the dual-recognition site to investigate the potential correlation of Exosomal glycosylation with polarization of THP-1 cells toward the tumor-suppressive M1 phenotype. Overall, this strategy provides a universal tool for multiple analyses of diverse protein-specific glycosylated exosomes, exhibiting enormous potential to explore exosome function and search for new early diagnosis markers.

Recent progress in quantitative technologies for the analysis of cancer-related exosome proteins.

Exosomes are a kind of extracellular vesicles, which play a significant role in intercellular communication and molecular exchange. Cancer-derived exosomes are potential and ideal biomarkers for the early diagnosis and treatment monitoring of cancers because of their abundant biological information and contribution to the interaction between cancer cells and the tumor microenvironment. However, there are a number of drawbacks, such as low sensitivity and tedious steps, in conventional detection techniques. Furthermore, exosome quantification is not enough to accurately distinguish cancer patients from healthy individuals. Therefore, developing efficient, accurate, and inexpensive exosome surface protein analysis techniques is necessary and critical. In recent years, a considerable number of researchers have presented novel detection strategies in this field. This review summarizes the recent progress in quantitative technologies for the analysis of cancer-related exosome proteins, mainly including the detection methods based on aptamers, nanomaterials, and antibodies, discusses a roadmap for future developments, and aims to offer an innovative perspective of exosome research.

Bilateral endobronchial metastases from hepatocellular carcinoma (HCC): A case report with literature review.

Hepatocellular carcinoma presenting with endobronchial metastases is extremely rare, with less than 15 cases reported over the last 4 decades. We describe a case of a 62-year-old male who first presented with pulmonary symptoms secondary to bilateral endobronchial metastatic disease from newly diagnosed hepatocellular carcinoma.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting.

Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

A New Predictive Nomogram for the Risk of Delayed Incision Healing After Open Posterior Lumbar Surgery: A Retrospective Study.

STUDY DESIGN: This was a primary research study. OBJECTIVE: A risk nomogram was established and externally validated by exploring the related risk factors for delayed incision healing in patients undergoing open posterior lumbar surgery. SUMMARY OF BACKGROUND DATA: The use of a nomogram model to predict prognosis in patients with delayed incision healing is an evolving field given the complex presentation of patients with this condition. PATIENTS AND METHODS: This study reviewed 954 patients with data collected from January 2017 to December 2021 who were randomized into a training set and a validation set (7:3). We built a prediction model based on a training set of 616 patients. The "least absolute shrinkage and selection operator" regression model was applied to screen out the optimal prediction features, and binary logistic regression was used to develop a prediction model. The discrimination, calibration, and clinical applicability of the prediction model were assessed by using the area under the curve, C -index, calibration curve, and decision curve analysis. RESULTS: Postoperative delayed incision healing occurred in 214 (24.4%) patients. The least absolute shrinkage and selection operator regression model showed that smoking, white blood cell count, infection, diabetes, and obesity were involved in delayed incision healing ( P ≠ 0). A binary logistic regression model confirmed that smoking [odds ratio (OR) = 3.854, 95% CI: 1.578~9.674, P = 0.003], infection (OR = 119.524, 95% CI: 59.430~263.921, P < 0.001), diabetes (OR = 3.935, 95% CI: 1.628~9.703, P = 0.003), and obesity (OR = 9.906, 95% CI: 4.435~23.266, P < 0.001) were predictors of delayed incision healing, and a nomogram model was established. The area under the curve was 0.917 (95% CI: 0.876-0.959). The calibration curve showed good consistency. Decision curve analysis showed that when the risk threshold of delayed incision healing was >5%, the use of this nomogram was more clinically valuable. CONCLUSIONS: Smoking, infection, diabetes, and obesity are risk factors for delayed incision healing. The nomogram model could be used to predict the risk of delayed incision healing and could provide a reference for early clinical intervention.

Visual Ordinal Coronary Artery Calcium Score from Non-Gated Chest CT Predicts Mortality After Severe Chronic Obstructive Pulmonary Disease Exacerbation.

Purpose: Chronic obstructive pulmonary disease (COPD) patients often undergo chest CT for various indications. Coronary artery calcium (CAC) can be quantified visually on ungated chest CT using an ordinal score that has been shown to correlate well with traditional Agatston CAC scoring. The prognostic role of CAC was studied mainly in stable COPD patients. We aim to study the association between ordinal CAC and mortality amongst patients admitted for acute exacerbation of COPD (AECOPD). Patients and Methods: Retrospective study of AECOPD cases with no previous coronary revascularization admitted between 1st January 2016 to 30th June 2017 with a chest CT performed during admission or within 365 days prior. Ordinal CAC scoring (scale of 0-12) was performed by an experienced CT cardiologist blinded to patient data and outcomes. Patient demographics and future clinical events were retrieved from electronic medical records. Results: There were 93 patients included (87.1% male, mean age 75 years) with the majority (59.1%) in GOLD Stage III. There were 21 (22.6%) patients with no CAC as well as 39 (41.9%) and 33 (35.5%) with ordinal CAC of 1-3 and 4-12, respectively. There were no significant differences in Charlson Comorbidity Index (CCI) and the proportion of patients with traditional cardiovascular risk factors (namely hypertension, dyslipidaemia, diabetes and smoking status) between the ordinal CAC score groups. Over a median follow-up period of 2.9 (1.1-3.9) years, there were 51 (54.8%) deaths. An ordinal CAC score of 4-12 was the only significant predictor of mortality after multivariate Cox-regression analysis adjustment for age, gender, body mass index, prior exacerbations, FEV1, cardiovascular risk factors and CCI [HR 3.944, (95% confidence interval 1.647-9.433, p = 0.002)]. Conclusion: Ordinal CAC measured from a current or recent ungated chest CT is an independent predictor of all-cause mortality in admitted AECOPD patients with no previous coronary revascularization.

Serum-based surface-enhanced Raman spectroscopy combined with PCA-RCKNCN for rapid and accurate identification of lung cancer.

Early and precise diagnosis of lung cancer is critical for a better prognosis. However, it is still a challenge to develop an effective strategy for early precisely diagnose and effective treatments. Here, we designed a label-free and highly accurate classification serum analytical platform for identifying mice with lung cancer. Specifically, the microarray chip integrated with Au nanostars (AuNSs) array was employed to measure the surface-enhanced Raman scattering (SERS) spectra of serum of tumor-bearing mice at different stages, and then a recognition model of SERS spectra was constructed using the principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) algorithm. The microarray chip can realize rapid, sensitive, and high-throughput detection of SERS spectra of serum. RCKNCN based on the PCA-generated features successfully differentiated the SERS spectra of serum of tumor-bearing mice at different stages with a classification accuracy of 100%. The most prominent spectral features for distinguishing different stages were captured in PCs loading plots. This work not only provides a practical SERS chip for the application of SERS technology in cancer screening, but also provides a new idea for analyzing the feature of serum at the spectral level.

Blockade of USP14 potentiates type I interferon signaling and radiation-induced antitumor immunity via preventing IRF3 deubiquitination.

PURPOSE: The adaptive immune responses induced by radiotherapy has been demonstrated to largely rely on STING-dependent type I interferons (IFNs) production. However, irradiated tumor cells often fail to induce dendritic cells (DCs) to produce type I IFNs. Hence, we aim to uncover the limitation of STING-mediated innate immune sensing following radiation, and identify efficient reagents capable to rescue the failure of type I IFNs induction for facilitating radiotherapy. METHODS: A targeted cell-based phenotypic screening was performed to search for active molecules that could elevate the production of type I IFNs. USP14 knockout or inhibition was assayed for IFN production and the activation of STING signaling in vitro. The mechanisms of USP14 were investigated by western blot and co-immunoprecipitation in vitro. Additionally, combinational treatments with PT33 and radiation in vivo and in vitro models were performed to evaluate type I IFNs responses to radiation. RESULTS: PT33 was identified as an enhancer of STING agonist elicited type I IFNs production to generate an elevated and durable STING activation profile in vitro. Mechanistically, USP14 inhibition or deletion impairs the deubiquitylation of K63-linked IRF3. Furthermore, blockade of USP14 with PT33 enhances DC sensing of irradiated-tumor cells in vitro, and synergizes with radiation to promote systemic antitumor immunity in vivo. CONCLUSION: Our findings reveal that USP14 is one of the major IFN production suppressors and impairs the activation of IRF3 by removing the K63-linked ubiquitination of IRF3. Therefore, blockage of USP14 results in the gain of STING signaling activation and radiation-induced adaptive immune responses.

Rapid On-Chip Isolation of Cancer-Associated Exosomes and Combined Analysis of Exosomes and Exosomal Proteins.

Exosomes are lipid bilayer extracellular vesicles secreted by various types of cells and inherit abundant molecular information from parental cells. Tumor-derived exosomes have been widely recognized as noninvasive biomarkers for early cancer diagnosis and surveillance, but the separation of intact exosomes and detection of exosomal proteins remain challenging. Herein, we proposed a microfluidic chip for specific exosome isolation, integrated with sensitive quantification by a novel PTCDI-aptamer signal switch strategy. To enhance the capture efficiency, an alternating drop-shaped micropillar array was designed to assist the capture of tumor-derived exosomes by Tim4-modified magnetic beads (Tim4 beads) on the chip. Following capture, a chelating agent can easily elute intact exosomes which were further used for profiling exosomal surface proteins by the multiplexed fluorescence turn-on approach. Profiting from the efficient on-chip enrichment of the Tim4 beads and superior fluorescence signal transduction strategy, the detection limit of the analysis platform for HepG2 exosomes is as low as 8.69 × 103 particles/mL with a wide linear range spanning 6 orders of magnitude. Meanwhile, the proposed platform could recognize subtle changes in protein levels on the exosomal surface from various cell lines. More importantly, this strategy is successfully applied to analyze exosomes in human serum to distinguish liver cancer patients from healthy individuals. Combined analysis of different types of biomarkers on the exosomal membrane surface can greatly improve the accuracy of cancer type identification and disease monitoring. We hope that this convenient, rapid, and sensitive platform may become a powerful tool in the field of exosome analysis and early cancer screening.

Treatments for Periductal Mastitis: Systematic Review and Meta-Analysis.

Introduction: Periductal mastitis (PDM) is a complex benign breast disease with a prolonged course and a high risk of recurrence after treatment. There are many available treatments for PDM, but none is widely accepted. This study aims to evaluate the various treatment failure rates (TFR) of different invasive treatment measures by looking at recurrence and persistence after treatment. In this way, it sets out to inform better clinical decisions in the treatment of PDM. Methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies about different treatment regimens provided to PDM patients that had been published before October 1, 2019. We included original studies written in English that reported the recurrence and/or persistence rates of each therapy. Outcomes were presented as pooled TFR and 95% CI for the TFR. Results: We included 27 eligible studies involving 1,066 patients in this study. We summarized 4 groups and 10 subgroups of PDM treatments, according to the published studies. Patients treated minimally invasively (group 1) were subdivided into 3 subgroups and pooled TFR were calculated as follows: incision and drainage (n = 73; TFR = 75.6%; 95% CI 27.3-100%), incision alone (n = 74; TFR = 20.1%; 95% CI 0-59.9%), and breast duct irrigation (n = 123; TFR = 19.4%; 95% CI 0-65.0%). Patients treated with a minor excision (excision of the infected tissue and related duct; group 2) were divided into 4 subgroups and pooled TFR were calculated as follows: wound packing alone (n = 127; TFR = 2.1%; 95% CI 0-5.2%), primary closure alone (n = 66; TFR = 37.1%; 95% CI 9.5-64.8%), primary closure under antibiotic treatment cover (n = 55; TFR = 4.8%; 95% CI 0-11.4%), and additional nipple part removal (n = 232; TFR = 9.6%; 95% CI 5.8-13.4%). Patients treated with a major excision (excision of the infected tissue and the major duct; group 3) included the following 2 subgroups: patients treated with a circumareolar incision (n = 142; TFR = 7.5%; 95% CI 0.4-14.7%) and patients treated with a radial incision of the breast (n = 78; TFR = 0.6%; 95% CI 0-3.6%). Group 4 contained patients receiving different major plastic surgeries. The pooled TFR of this group (n = 86) was 3.4% (95% CI 0-7.5%). Conclusion: Breast duct irrigation, which is the most minimally invasive of all of the treatment options, seemed to yield good outcomes and may be the first-line treatment for PDM patients. Minor excision methods, except for primary closure alone, might be enough for most PDM patients. Major excision, especially with radial incision, was a highly effective salvage therapy. The major plastic surgery technique was also acceptable as an alternative treatment for patients with large lesions and concerns about breast appearance. Incision and drainage and minor excision with primary closure alone should be avoided for PDM patients. Further research is still needed to better understand the etiology and pathogenesis of PDM and explore more effective treatments for this disease.

Prognostic significance of CD56 expression in patients with multiple myeloma: a meta-analysis.

OBJECTIVES: Several studies have demonstrated the expression status of CD56 was associated with prognosis in multiple myeloma (MM) patients, the prognostic significance remains controversial. Here, the prognostic value of CD56 is further investigated in MM patients. METHODS: We systematically searched the databases including PubMed, EMBASE, Web of Science and the Cochrane Library. The hazard ratios (HRs) with their 95% confidence intervals (CIs) were pooled to evaluate the relationship between CD56 and overall survival (OS) and progress-free survival (PFS). RESULTS: A total of 14 studies covering 1365 patients were included in this meta-analysis. The results revealed that CD56 negativity in MM was associated with poorer OS (HR = 1.83, 95% CI = 1.29-2.60, P = 0.001) and PFS (HR = 1.57, 95% CI = 1.27-1.95, P = 0.000). Subgroup analysis further demonstrated that there was an effect of treatment regimen, detection method, survival analysis, study region and the cut-off value of CD56 on CD56 expression. DISCUSSION AND CONCLUSION: The meta-analysis suggested that CD56 negative patients had a poor prognosis for OS in Asian patients and for PFS in non-Asian patients. Novel drugs didn't show a significant improvement or overcome on the adverse prognosis brought by CD56 negativity. For patients undergone autologous stem-cell transplantation (ASCT), the poor prognosis was overcome by the treatment, which shed a light on the prognostic judgment and individualized treatment.

Predictors of Influenza PCR Positivity in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

PURPOSE: Influenza infection is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Clinical features predicting influenza PCR positivity are unknown. We aim to identify predictors of influenza PCR positivity in AECOPD. PATIENTS AND METHODS: A retrospective study of AECOPD cases admitted between 1st January 2016 to 30 June 2017 with combined nasal/throat swabs sent for influenza PCR (Xpert Xpress Flu/RSV) within 24 hours of admission was performed. Clinical parameters and investigations within 24 hours of admission were retrieved from electronic medical records. RESULTS: Influenza PCR were sent for 925 AECOPD cases (mean age 75 years, 87.9% male). There were 90 PCR positive cases (68 Influenza A, 22 Influenza B). Influenza PCR positive cases had higher temperatures, higher heart rates, lower white cell and lower eosinophil counts. Age, gender, COPD severity, comorbidities and smoking status were similar in both groups. There were no differences in blood pressure, oxygen status, neutrophil or lymphocyte counts, C reactive protein, procalcitonin or chest X-ray consolidation between groups. Higher temperature, higher heart rate, white cell count in the lowest quartile (Q1 < 8.1 x109/L) and non-eosinophilic exacerbations predicted influenza PCR positivity on univariate logistic regression and these factors remained significant after multivariate adjustment (temperature adjusted odds ratio [adj OR] 1.324 [1.009-1.737], p = 0.043; heart rate adj OR 1.017 [1.004-1.030], p = 0.011; white cell count Q1 adj OR 3.330 [1.690-6.562], p = 0.001; eosinophilic exacerbations adj OR 0.390 [0.202-0.756], p = 0.005). CONCLUSION: Higher temperature, higher heart rate, low white cell count (especially when < 8.1 x109/L) and non-eosinophilic exacerbations are independent predictors of influenza PCR positivity in AECOPD cases.

High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap? STUDY DESIGN: Prospective, observational, cross-sectional study. METHODS: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes. RESULTS: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity. CONCLUSIONS: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.

Membrane-Decorated Exosomes for Combination Drug Delivery and Improved Glioma Therapy.

Glioblastoma multiforme (GBM) is the most aggressive tumor of the central nervous system in adults. The standard therapy of GBM fails to eradicate it due to the drug resistance of glioblastoma stem cells (GSCs) and the presence of the blood-brain-barrier (BBB). Temozolomide (TMZ) is the first-line anti-GBM drug after surgery. However, the high activity of O6-alkylguanine-DNA alkyltransferase (AGT) limits the therapeutic effect of TMZ. Herein, we reported dual-receptor-specific exosomes as vehicles loaded with TMZ and O6-benzylguanine (BG) for eradicating TMZ-resistant GBM. Exosomes pose great promise as nanocarriers due to their intrinsic low immunogenicity, strong cargo-protective capacity, ideal size range, and natural penetration ability of the blood-brain-barrier (BBB). The target ligands angiopep-2 and CD133 RNA aptamers were conjugated on exosomes via an amphiphilic molecule bridge, which was induced to express on donor cells. The resulting nanocarriers exhibited efficient uptake by U87MG and GSCs, excellent BBB penetration ability, and perfect GBM accumulation due to An2 and CD133 aptamer functionalization. Such superior properties of the two dual-receptor-specific exosomes resulted in excellent in vitro proliferation inhibition of U87MG and GSCs and extension of the median survival time of U87MG-bearing mice, without causing adverse effects. The formed exosome nanocomposites can serve as powerful nanomedicine for GBM therapy and provide a promising avenue for targeted therapy against other diseases of the central nervous system.

An artificial enzyme cascade amplification strategy for highly sensitive and specific detection of breast cancer-derived exosomes.

Tumor-related exosomes, which are heterogeneous membrane-enclosed nanovesicles shed from cancer cells, have been widely recognized as potential noninvasive biomarkers for early cancer diagnosis. Herein, an artificial enzyme cascade amplification strategy based on a switchable DNA tetrahedral (SDT) scaffold was proposed for quantification of breast cancer-derived exosomes. The SDT scaffold is composed of G-quadruplex mimicking DNAzyme sequences on its two single-stranded edges and glucose oxidase (GOx) on the four termini of the complementary strands. In the initial state, the SDT scaffold is blocked by the switch strand which consists of partial complementary domains with the DNA tetrahedron and a MUC1 aptamer. MCF-7 exosomes could release the quadruplex-forming sequences through the recognition of the MUC1 aptamer. The newly formed DNAzyme brings GOx into spatial proximity and induces high-efficiency enzyme cascade catalytic reactions on the SDT. Consequently, high sensitivity toward MCF-7 exosome analysis was obtained with a wide linear range of 3.8 × 106 to 1.2 × 108 particles per mL and a limit of detection of 1.51 × 105 particles per mL. In addition, such a DNAzyme reconfiguration strategy was able to distinguish MCF-7 exosomes from other breast cancer cell derived exosomes, indicating its excellent method specificity. The proposed enzyme cascade strategy not only provides a novel signal transformation and amplification nanoplatform for quantifying the specific populations of exosomes, but also can be further expanded to the analysis of multiple cancer biomarkers.