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Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC. A thermophoretic aptasensor can be used to profile cancer-associated proteins of extracellular vesicles (EVs) in patients’ plasma. Here, the authors use this technique to develop an EV-signature able to discriminate metastatic breast cancer, monitor treatment response, and predict patients’ progression-free survival.

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans. Triple-negative breast cancer (TNBC) lacks precise diagnostic and monitoring methods due to limited biomarkers. Here the authors develop a lectin-based thermophoretic assay (EVLET) that combines vibrating membrane filtration and thermophoretic amplification for efficient extracellular vesicle (EV) glycan profiling in the plasma of TNBC patients, enabling non-invasive cancer management by leveraging EV glycans.

Background Seeking positive and comprehensive rehabilitation methods after stroke is an urgent problem to be solved, which is very important to improve the dysfunction of stroke. The aim of this study was to investigate the effects of motor imagery-based brain-computer interface training (MI-BCI) on upper limb function and attention in stroke patients with hemiplegia. Methods Sixty stroke patients with impairment of upper extremity function and decreased attention were randomly assigned to the control group (CR group) or the experimental group (BCI group) in a 1:1 ratio. Patients in the CR group received conventional rehabilitation. Patients in the BCI group received 20 min of MI-BCI training five times a week for 3 weeks (15 sessions) in addition to conventional rehabilitation. The primary outcome measures were the changes in Fugl-Meyer Motor Function Assessment of Upper Extremities (FMA-UE) and Attention Network Test (ANT) from baseline to 3 weeks. Results About 93% of the patients completed the allocated training. Compared with the CR group, among those in the BCI group, FMA-UE was increased by 8.0 points (95%CI, 5.0 to 10.0; P  < 0.001). Alert network response time (32.4ms; 95%CI, 58.4 to 85.6; P  < 0.001), orienting network response (5.6ms; 95%CI, 29.8 to 55.8; P  = 0.010), and corrects number (8.0; 95%CI, 17.0 to 28.0; P  < 0.001) also increased in the BCI group compared with the CR group. Additionally, the executive control network response time (− 105.9ms; 95%CI, − 68.3 to − 23.6; P  = 0.002), the total average response time (− 244.8ms; 95%CI, − 155.8 to − 66.2; P  = 0.002), and total time (− 122.0ms; 95%CI, − 80.0 to − 35.0; P  = 0.001) were reduced in the BCI group compared with the CR group. Conclusion MI-BCI combined with conventional rehabilitation training could better enhance upper limb motor function and attention in stroke patients. This training method may be feasible and suitable for individuals with stroke. Trial registration : This study was registered in the Chinese Clinical Trial Registry with Portal Number ChiCTR2100050430(27/08/2021).

The enhanced membrane stability and chemical versatility of polymeric vesicles have made them promising tools in micro/nanoreactors, drug delivery, cell mimicking, etc. However, shape control over polymersomes remains a challenge and has restricted their full potential. Here we show that local curvature formation on the polymeric membrane can be controlled by applying poly( N -isopropylacrylamide) as a responsive hydrophobic unit, while adding salt ions to modulate the properties of poly( N -isopropylacrylamide) and its interaction with the polymeric membrane. Polymersomes with multiple arms are fabricated, and the number of arms could be tuned by salt concentration. Furthermore, the salt ions are shown to have a thermodynamic effect on the insertion of poly( N -isopropylacrylamide) into the polymeric membrane. This controlled shape transformation can provide evidence for studying the role of salt ions in curvature formation on polymeric membranes and biomembranes. Moreover, potential stimuli-responsive non-spherical polymersomes can be good candidates for various applications, especially in nanomedicine. Polymeric vesicles are promising candidates for use in a range of applications including drug delivery and cell mimics, however, control over the shape is still a challenge. Here, the authors report control over local curvature formation by addition of salt ions and stimuli responsive polymer to modulate its interaction with polymeric membrane.

The tactile pressure sensor is of great significance in flexible electronics, but sensitivity customization over the required working range with high linearity still remains a critical challenge. Despite numerous efforts to achieve high sensitivity and a wide working range, most sensitive microstructures tend to be obtained only by inverting naturally existing templates without rational design based on fundamental contact principles or models for piezoresistive pressure sensors. Here, a positive design strategy with a hyperelastic model and a Hertzian contact model for comparison was proposed to develop a flexible pressure sensor with highly customizable linear sensitivity and linearity, in which the microstructure distribution was precalculated according to the desired requirement prior to fabrication. As a proof of concept, three flexible pressure sensors exhibited sensitivities of 0.7, 1.0, and 1.3 kPa−1 over a linear region of up to 200 kPa, with a low sensitivity error (<5%) and high linearity (~0.99), as expected. Based on the superior electromechanical performance of these sensors, potential applications in physiological signal recognition are demonstrated as well, and such a strategy could shed more light on demand-oriented scenarios, including designable working ranges and linear sensitivity for next-generation wearable devices.

The mechanisms that promote the generation of new coronary vasculature during cardiac homeostasis and after injury remain a fundamental and clinically important area of study in the cardiovascular field. Recently, it was reported that mesenchymal-to-endothelial transition (MEndoT) contributes to substantial numbers of coronary endothelial cells after myocardial infarction. Therefore, the MEndoT has been proposed as a paradigm mediating neovascularization and is considered a promising therapeutic target in cardiac regeneration. Here, we show that preexisting endothelial cells mainly beget new coronary vessels in the adult mouse heart, with essentially no contribution from other cell sources through cell-lineage transdifferentiation. Genetic-lineage tracing revealed that cardiac fibroblasts expand substantially after injury, but do not contribute to the formation of new coronary blood vessels, indicating no contribution of MEndoT to neovascularization. Moreover, genetic-lineage tracing with a pulse-chase labeling strategy also showed that essentially all new coronary vessels in the injured heart are derived from preexisting endothelial cells, but not from other cell lineages. These data indicate that therapeutic strategies for inducing neovascularization should not be based on targeting presumptive lineage transdifferentiation such as MEndoT. Instead, preexisting endothelial cells appear more likely to be the therapeutic target for promoting neovascularization and driving heart regeneration after injury.

Background Acute coronary syndrome (ACS) is a serious cardiovascular disease that severely affects the quality of life and longevity of patients. MicroRNAs (miRNAs) play a key role in the progression of ACS with significant clinical value. The aim of this study was to examine the clinical value of miR-223-5p in ACS and on the occurrence of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). Methods The plasma expression of miR-223-5p was detected by RT-qPCR. The correlation of miR-223-5p and cTnI or Gensini score was shown by the Pearson method. Risk factors for the development of ACS were analyzed by multivariate logistic regression. The efficacy of miR-223-5p in identifying patients with ACS was shown by ROC curve. The predictive value of miR-223-5p for MACE development in ACS patients within 6 months after PCI was assessed by Kaplan-Meier curve and multivariate Cox regression. Results miR-223-5p levels were markedly elevated in ACS patients. miR-223-5p was found to be positively related to cTnI or Gensini score. miR-223-5p was a risk factor for ACS and significantly identified patients with ACS. MACE was more likely to occur after PCI in patients with high miR-223-5p levels, and miR-223-5p was an independent prognostic indicator of MACE. Conclusions miR-223-5p had diagnostic value for ACS and predicted MACE after PCI.

Background Coffee is widely consumed in the US, linked to various health benefits, including reduced adiposity. α-Klotho is a circulating protein linked to the aging processes, associated with greater longevity, and confers protective effects against cardiovascular disease, chronic kidney disease, and neurodegenerative disorders. This study investigates the association between coffee (total, caffeinated, and decaffeinated) intake and serum α-Klotho (SαKl) levels. Methods Data from 9,811 participants aged 40–79 years from the National Health and Nutrition Examination Survey (2007–2016) were analyzed. Coffee intake was assessed using 24-h dietary recalls in the Food and Nutrient Database for Dietary Studies. SαKl levels were measured using enzyme-linked immunosorbent assay. Multivariable linear regression and generalized additive models analyzed the relationships. Results An L-shaped association was observed between total coffee and caffeinated coffee intake and SαKl levels, characterized by a sharp decline at low consumption that plateaued at higher intakes, particularly among females and individuals under 60 years old. The relationship persisted across all adjusted models, with a clear inflection point in the L-shaped curve. Decaffeinated coffee showed no significant effects. Conclusion There is a negative, L-shaped association between coffee, particularly caffeinated coffee, and SαKl levels, underscoring the potential impact of caffeinated coffee on aging-related biomarkers and the need for further investigation into underlying mechanisms.

The systemic immune-inflammation index (SII) is a cost-efficient indicator for carcinoma prognosis. However, its utility in urothelial carcinoma (UC) prognosis is disputed. This meta-analysis aims to assess SII's prognostic value in UC. A thorough search of databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus, was conducted to find studies until January 11, 2023. Eligibility criteria were applied to select studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies and compiled in a meta-analysis to gauge SII's association with survival outcomes such as overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS). This analysis includes 19 studies with 12505 UC patients. It was found that high SII significantly correlated with worse OS in UC patients (HR 1.430, 95% CI 1.237-1.653, P<0.001). High SII values also linked with poorer CSS (HR 1.913, 95% CI 1.473-2.485, P<0.001), RFS (HR 1.240, 95% CI 1.097-1.403, P=0.001), and PFS (HR 1.844, 95% CI 1.488-2.284, P<0.001) compared to low SII values. Subgroup analysis revealed SII's consistent prognostic value in UC across races, carcinoma types, sample sizes, and SII cut-off values, suggesting its potential as a prognostic indicator in UC patients. Current evidence suggests SII as a promising, cost-efficient predictor in UC patients. This meta-analysis indicates SII's potential as a valuable prognostic tool in UC patients. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307643, identifier CRD42022307643.

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane 1 . Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes 2 , 3 , investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19. Through integration of lipidomic and proteomic analyses of exosomes from patients with COVID-19, Lam et al. find that exosomes from different stages of infection have distinct compositions and can evoke distinct responses in recipient cells.