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With an evolving understanding and new discoveries in extracellular vesicle (EV) biology and their implications in health and disease, the significant diagnostic and therapeutic potential of EVs for vision research has gained recognition. In 2021, the National Eye Institute (NEI) unveiled its Strategic Plan titled Vision for the Future (2021-2025), which listed EV research as a priority within the domain of Regenerative Medicine, a pivotal area outlined in the Plan. In alignment with this prioritization, NEI organized a workshop inviting twenty experts from within and beyond the visual system. The workshop aimed to review current knowledge in EV research and explore gaps, needs and opportunities for EV research in the eye, including EV biology and applications of EVs in diagnosis, therapy and prognosis within the visual system. This perspective encapsulates the workshops deliberations, highlighting the current landscape and potential implications of EV research in advancing eye health and addressing visual diseases.

Ovarian cancer (OC) is the third most common malignant tumor of women and is accompanied by an alteration of systemic metabolism. A liquid biopsy that captures and detects tumor-related biomarkers in body fluids has great potential for OC diagnosis. EVs, nanosized extracellular vesicles found in the blood, have been proposed as promising biomarkers for liquid biopsies. In this study we recruited 37 OC patients, 22 benign ovarian tumor (BE) patients, and 46 clinically healthy control patients (CON). Plasma EVs were purified from blood samples and sensitive thermal separation probe-based mass spectrometry analysis using a global untargeted metabolic profiling strategy was employed to characterize the metabolite fingerprints. Uniform manifold approximation and projection (UMAP) analysis demonstrated a distinct separation of EVs among the three groups. We screened for diagnostic biomarkers from plasma EV metabolites using seven machine learning algorithms, including artificial neural network (ANN), decision tree (DT), K nearest neighbor (KNN), logistics regression (LR), Naïve Bayes (NB), random forest (RF), and support vector machine (SVM). For the OC-CON comparison, the highest AUC values were found for RF (0.91), ANN (0.90) and NB (0.90), with the F1-scores of 0.88, 0.83, and 0.76 respectively. For the OC-BE comparison, SVM (0.94), RF (0.86), and KNN (0.86) gave the highest AUCs, with F1-scores of 0.80, 0.80, and 0.91 respectively. A total of 19 and 158 metabolic features exhibited significant differences (FC = 1.5, q < 0.01) in the OC vs BE and OC vs CON comparisons, respectively. Notably, the quantities of 9-octadecenamide and 1,4-methanobenzocyclodecene were significantly elevated, while maltol showed a significant reduction in the OC group compared to the BE group. When comparing the OC group to the CON group, the concentrations of 4-amino-furazan-3-carboxylic acid 2-hydroxy-4-methoxybenzaldehyde, N-phenylethyl, and 4-morpholineethanamine were significantly elevated, while the remaining metabolites, including hydrazine and pyridine sulfonamide, were reduced, in the OC group. The metabolites showing different abundancies are associated with cancer-related mutations, immune responses, and metabolic reprogramming. We demonstrate that the RF algorithm, combined with sensitive thermal separation probe-based mass spectrometry analysis of plasma EVs, can effectively identify OC patients with good accuracy. Thus, our study has shortlisted a set of potential biomarkers in plasma EVs, and the proposed approach could serve as a routine prescreening tool for ovarian cancer. [ABSTRACT FROM AUTHOR]

In current times, sustainability is paramount, and businesses are increasingly adopting renewable energy sources (RESs) and electric vehicle (EV) charging infrastructure to minimise their environmental impact and operational costs. Such a transition can prove challenging to multi-location businesses since each chain store functions under different constraints; therefore, the implementation of a corporate policy requires adaptations. The increased electricity demand associated with EV charging stations and their installation cost could prove to be a significant financial burden. Therefore, this study aims to investigate and develop strategies for effectively incorporating RES and EV charging stations into the operations of a supermarket chain in Crete. Monthly electricity consumption data, parking availability, and premise dimensions were collected for 20 supermarkets under the same brand. To achieve a more tailored approach to custom energy system sizing, the integration of energy storage coupled with a photovoltaic (PV) system was investigated, using the Moth–Flame Optimiser (MFO) to maximise the Net Present Value (NPV) of 20 years. The algorithm managed to locate optimal solutions that yield profitable installations for all supermarkets by installing the necessary number of PV units. Manual exploration around the solutions led to the optimal integration of energy storage systems with a total upfront cost of EUR 856,477.00 and a total profit for the entire brand equal to EUR 6,426,355.14. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus, a common pathogen, is capable of producing a significant array of toxins and can develop biofilms or small colony variants (SCVs) to evade detection by the immune system and resist the effects of antibiotics. Its ability to persist for extended periods within host cells has led to increased research interest. This review examines the process of internalization of S. aureus, highlighting the impact of its toxins and adhesion factors on host cells. It elucidates the intricate interactions between them and the host cellular environment, thereby offering potential strategies for the treatment and prevention of S. aureus infections. [ABSTRACT FROM AUTHOR]

The sustainable integration of distributed energy resources (DER) into distribution networks requires accurate forecasting of hosting capacity. The network and DER variables alone do not capture the full range of external influences on DER integration. Traditional models often overlook the dynamic impacts of these exogenous factors, leading to suboptimal predictions. This study introduces a Sensitivity-Enhanced Recurrent Neural Network (SERNN) model, featuring a sensitivity gate within the neural network's memory cell architecture to enhance responsiveness to time-varying variables. The sensitivity gate dynamically adjusts the model's response based on external conditions, allowing for improved capture of input variability and temporal characteristics of the distribution network and DER. Additionally, a feedback mechanism within the model provides inputs from previous cell states into the forget gate, allowing for refined control over input selection and enhancing forecasting precision. Through case studies, the model demonstrates superior accuracy in hosting capacity predictions compared to baseline models like LSTM, ConvLSTM, Bidirectional LSTM, Stacked LSTM, and GRU. Study shows that the SERNN achieves a mean absolute error (MAE) of 0.2030, a root mean square error (RMSE) of 0.3884 and an R-squared value of 0.9854, outperforming the best baseline model by 48 per cent in MAE and 71 per cent in RMSE. Additionally, Feature engineering enhances the model's performance, improving the R-squared value from 0.9145 to 0.9854. The sensitivity gate also impacts the model's performance, lowering MAE to 0.2030 compared to 0.2283 without the sensitivity gate, and increasing the R-squared value from 0.9152 to 0.9854. Incorporating exogenous factors such as the time of day as a sensitivity gate input, further improves responsiveness, making the model more adaptable to real-world conditions. This advanced SERNN model offers a reliable framework for distribution network operators, supporting intelligent planning and proactive DER management. Ultimately, it provides a significant step forward in hosting capacity analysis, enabling more efficient and sustainable DER integration within next-generation distribution networks. [ABSTRACT FROM AUTHOR]

Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation. In addition to their role in allergic inflammation, MCs are components of the tumor microenvironment (TME). MicroRNAs (miRNAs) are small RNA molecules that do not encode proteins, but regulate post-transcriptional gene expression by binding to the 3' non-coding regions of mRNAs. This plays a crucial role in the function of MC, including the key processes of MC proliferation, maturation, apoptosis, and activation. It has been demonstrated that miRNAs are also present in extracellular vesicles (EVs) secreted by MCs. EVs derived from MCs mediate intercellular communication by carrying miRNAs, affecting various diseases including allergic diseases, intestinal disorders, neuroinflammation, and tumors. These findings provide important insights into the therapeutic mechanisms and targets of miRNAs in MCs that affect diseases. This review discusses the relevance of miRNA production by MCs in regulating their own activity and the effect of miRNAs putatively produced by other cells in the control of MC activity and their participation in selected pathologies. [ABSTRACT FROM AUTHOR]

Neutrophils interact with Leishmania when the sandfly vector inoculates these parasites in the host with saliva and promastigotes-derived extracellular vesicles (EVs). It has been shown that this co-injection induces inflammation and exacerbates leishmaniasis lesions. EVs are a heterogeneous group of vesicles released by cells that play a crucial role in intercellular communication. Neutrophils are among the first cells to interact with the parasites and release neutrophil extracellular traps (NETs) that ensnare and kill the promastigotes. Here, we show that Leishmania amazonensis EVs induce NET formation and identify molecular mechanisms involved. We showed the requirement of neutrophils' toll-like receptors for EVs-induced NET. EVs carrying the virulence factors lipophosphoglycan and the zinc metalloproteases were endocytosed by some neutrophils and snared by NETs. EVs-induced NET formation required reactive oxygen species, myeloperoxidase, elastase, peptidyl arginine deiminase, and Ca++. The proteomic analysis of the EVs cargo revealed 1,189 proteins; the 100 most abundant identified comprised some known Leishmania virulent factors. Importantly, L. amazonensis EVs-induced NETs lead to the killing of promastigotes and could participate in the exacerbated inflammatory response induced by the EVs, which may play a role in the pathogenesis process. [ABSTRACT FROM AUTHOR]

In the context of the integration of hybrid energy storage systems (HESSs) and electric vehicles (EVs), this paper investigates the load frequency control (LFC) issue of the power system. Weighting coefficients are set for the generators, HESSs and EVs, respectively, to show their different abilities to regulate the power system. A fuzzy logic-based sliding mode control approach is designed to ensure the stable performance of the LFC power system integrated with HESSs and EVs. The improvement of the proposed method is the application of the linear matrix inequality (LMI) toolbox in fuzzy controller design, which solves the limitations and uncertainties caused by trial-error or experience in common fuzzy controllers. There is no general form for the membership function of the fuzzy control. This paper presents a design approach for the membership function based on the calculation results of LMI. Simulations are tested on an IEEE 39-bus system integrated with HESSs and EVs. The simulation results prove that the proposed method reduces the time required for the power system frequency to reach stability by approximately 8.8 % , demonstrating the superiority and usability of the proposed approach. [ABSTRACT FROM AUTHOR]

Electric vehicles (EVs) have attracted significant attention in recent years primarily due to minimal adverse impact on the environment and efficiency of running costs. Although use of EVs brings noticeable benefits to users and the overall society, deployment of EVs, new carbon control regulations and interactive utility models are creating a compression on current electricity system. Further, due to the growth in adoption of EVs, the demand for electricity is expected to increase significantly over the next few years which can result in low-voltage networks. Since traditional networks are not designed for such loads, it can lead to inadmissible network conditions and resource overloads, which require network expansion through decentralized power generation. Distributed energy resources (DERs) such as smart grids leverage emerging technologies including internet of things (IoT) to achieve efficient energy management system. The aim of this research is to facilitate peer-to-peer energy distribution solution by focusing on the challenge of a decentralized, transparent reward system to achieve incentivization of power generation and distribution at microgrid level. Leveraging inherent benefits of blockchain technology, we develop a blockchain-based decentralized electricity trading platform to incentivize power generation at such micro level. Our platform allows local communities to contribute to meet the increased electricity demands by trading the generated electricity directly to EVs in a trusted and secure P2P environment while keeping the sustainability of the generated energy to balance demand and generation. We include detailed design specification, implementation and evaluation of the proposed electricity trading platform to assess feasibility of such system to be utilized within a production-level system. [ABSTRACT FROM AUTHOR]

Violacein is a natural indole-derived purple pigment of microbial origin that has attracted attention for its remarkable biological properties. Due to its poor solubility in aqueous media, most studies of this pigment use extracts of the compound obtained with common solvents. Violacein is also transported in bacterial extracellular vesicles (EVs) and transferred via this type of carrier remains stable in an aqueous environment. This paper is the first to present an in-depth study of Janthinobacterium lividum EVs as violacein carriers. J. lividum EVs were studied for their contribution to violacein translocation, size, morphology and protein composition. The production of violacein encapsulated in EVs was more efficient than the intracellular production of this compound. The average size of the violacein-containing EVs was 124.07 ± 3.74 nm. Liquid chromatography-tandem mass spectrometry analysis (LC–MS/MS) revealed 932 proteins common to three independent EVs isolations. The high proportion of proteins with intracellular localisation, which are involved in many fundamental cellular processes, suggests that J. lividum EVs could be generated in a cell lysis model, additionally stimulated by violacein production. Using human keratinocytes and melanoma cell lines, it was confirmed that J. lividum EVs are able to react with and deliver their cargo to mammalian cells. The EVs-delivered violacein was shown to retain its activity against melanoma cells, and the dose and timing of treatment can be selected to target only cancer cells. The characterisation of J. lividum EVs, described in the following paper, represents a milestone for their future potential anticancer application. Key points: • This report focuses on the investigation of Janthinobacterium lividum EVs as a new delivery vehicle for violacein, a compound with a previously demonstrated broad spectrum of activity. • EVs were characterised for size, morphology and protein composition. • Studies on human keratinocytes and a melanoma cell model confirmed that the activity of violacein applied in the encapsulated form of EVs is similar to that of its organic solvent extract, but their production is much more environmentally friendly. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are heterogeneous entities secreted by cells into their microenvironment and systemic circulation. Circulating EVs carry functional small RNAs and other molecular footprints from their cell of origin, and thus have evident applications in liquid biopsy, therapeutics, and intercellular communication. Yet, the complete transcriptomic landscape of EVs is poorly characterized due to critical limitations including variable protocols used for EV‐RNA extraction, quality control, cDNA library preparation, sequencing technologies, and bioinformatic analyses. Consequently, there is a gap in knowledge and the need for a standardized approach in delineating EV‐RNAs. Here, we address these gaps by describing the following points by (1) focusing on the large canopy of the EVs and particles (EVPs), which includes, but not limited to – exosomes and other large and small EVs, lipoproteins, exomeres/supermeres, mitochondrial‐derived vesicles, RNA binding proteins, and cell‐free DNA/RNA/proteins; (2) examining the potential functional roles and biogenesis of EVPs; (3) discussing various transcriptomic methods and technologies used in uncovering the cargoes of EVPs; (4) presenting a comprehensive list of RNA subtypes reported in EVPs; (5) describing different EV‐RNA databases and resources specific to EV‐RNA species; (6) reviewing established bioinformatics pipelines and novel strategies for reproducible EV transcriptomics analyses; (7) emphasizing the significant need for a gold standard approach in identifying EV‐RNAs across studies; (8) and finally, we highlight current challenges, discuss possible solutions, and present recommendations for robust and reproducible analyses of EVP‐associated small RNAs. Overall, we seek to provide clarity on the transcriptomics landscape, sequencing technologies, and bioinformatic analyses of EVP‐RNAs. Detailed portrayal of the current state of EVP transcriptomics will lead to a better understanding of how the RNA cargo of EVPs can be used in modern and targeted diagnostics and therapeutics. For the inclusion of different particles discussed in this article, we use the terms large/small EVs, non‐vesicular extracellular particles (NVEPs), EPs and EVPs as defined in MISEV guidelines by the International Society of Extracellular Vesicles (ISEV). [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is an aggressive brain cancer with a highly immunosuppressive tumor microenvironment (TME), invariably infiltrated by tumor-associated macrophages (TAMs). These TAMs resemble M2 macrophages, which promote tumor growth and suppress immune responses. GBM cells secrete extracellular vesicles (EVs) containing microRNA-25, which inhibits the cGAS-STING pathway and prevents TAMs from adopting a pro-inflammatory M1 phenotype. This study characterizes antimiR-25/cGAMP nanocomplexes (NCs) for potential therapeutic applications. A particle size analysis revealed a significant reduction upon complexation with antimiR-25, resulting in smaller, more stable nanoparticles. Stability tests across pH levels (4–6) and temperatures (25–37 °C) demonstrated their resilience in various biological environments. Biological assays showed that antimiR-25 NCs interacted strongly with transferrin (Tf), suggesting potential for blood–brain barrier passage. The use of cGAMP NCs activated the cGAS-STING pathway in macrophages, leading to increased type I IFN (IFN-β) production and promoting a shift from the M2 to M1 phenotype. The combined use of cGAMP and antimiR-25 NCs also increased the expression of markers involved in M1 polarization. These findings offer insights into optimizing antimiR-25/cGAMP NCs for enhancing immune responses in GBM. [ABSTRACT FROM AUTHOR]

Neutrophils release extracellular vesicles, and some subsets of neutrophil-derived extracellular vesicles are procoagulant. In response to Staphylococcus aureus , neutrophils produce extracellular vesicles that associate electrostatically with neutrophil extracellular traps. DNA in neutrophil extracellular traps is procoagulant, but whether neutrophil extracellular vesicles produced during bacterial challenge have similar activity is unknown. Given that extracellular vesicle activity is agonist and cell-type dependent and coagulation contributes to sepsis, we hypothesized that sepsis-causing bacteria increase production of neutrophil-derived extracellular vesicles, as well as extracellular vesicle–associated DNA, and intact extracellular vesicles and DNA cause coagulation. We recovered extracellular vesicles from neutrophils challenged with S. aureus , Staphylococcus epidermidis , Escherichia coli , and Pseudomonas aeruginosa and measured associated DNA and procoagulant activity. Extracellular vesicles from S. aureus –challenged neutrophils, which were previously characterized, displayed dose-dependent procoagulant activity as measured by thrombin generation in platelet-poor plasma. Extracellular vesicle lysis and DNase treatment reduced thrombin generation by 90% and 37%, respectively. S. epidermidis , E. coli , and P. aeruginosa also increased extracellular vesicle production and extracellular vesicle–associated extracellular DNA, and these extracellular vesicles were also procoagulant. Compared to spontaneously released extracellular vesicles, which demonstrated some ability to amplify factor XII–dependent coagulation in the presence of an activator, only extracellular vesicles produced in response to bacteria could initiate the pathway. S. aureus and S. epidermidis extracellular vesicles had more surface-associated DNA than E. coli and P. aeruginosa extracellular vesicles, and S. aureus and S. epidermidis extracellular vesicles contributed to initiation and amplification of thrombin generation in a DNA-dependent manner. However, DNA on E. coli or P. aeruginosa extracellular vesicles played no role, suggesting that neutrophils release procoagulant extracellular vesicles, which can activate the coagulation cascade through both DNA-dependent and independent mechanisms. [ABSTRACT FROM AUTHOR]

Background: Combining radiotherapy with targeted therapy benefits patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer (EGFRm NSCLC). However, the optimal strategy to combine EGFR tyrosine kinase inhibitors (TKIs) with radiotherapy for maximum efficacy and minimal toxicity is still uncertain. Notably, EVs, which serve as communication mediators among tumor cells, play a crucial role in the anti-tumor immune response. Methods To exploit the role of EVs in the delivery of tumor antigens, we formulated a therapeutic strategy that involves the use of radiation-induced tumor-derived EVs (TEXs) loaded onto dendritic cells (DCs) as a kind of vaccine in conjunction with EGFR TKIs and assessed the efficacy and safety of this approach in the treatment of EGFRm NSCLC. Results In our study, we characterized the release of immunogens as influenced by various modes of cell death, examining the impact of different levels of cell death under diverse irradiation modalities. Our results demonstrated that a radiation mode of 6Gy*3f exhibited the most promising potential to stimulate anti-tumor immune responses. This radiotherapy fraction, combined with TKIs, showed promising results in a tumor-bearing mouse model with an EGFR mutation, although there is a risk of radiation-associated pneumonitis. Furthermore, we found that 6Gy*3f-TEXs in vitro activate DCs and promote T cell proliferation as well as cytotoxic T lymphocyte-mediated tumor cell destruction. The administration of EGFR-TKIs combined DCs loaded with 6Gy*3f-TEXs exhibited the potential to inhibit tumor growth and mitigate the risk of pneumonitis. Together, the research shows that TEXs from high-dose fractionation radiation can mature DCs and boost the killing of cytotoxic T lymphocytes. Combining these DC vaccines with Osimertinib offers a promising and safe treatment for EGFRm NSCLC. [ABSTRACT FROM AUTHOR]

Currently, with outstanding advances in automated driving technology, modern vehicles with a variety of electronic control systems help improve traffic safety. One is the electronic stability adaptive control system that ensures the electric vehicle stays on track even in unpredictable situations such as driving on slippery roads, sudden movements, and changing direction of driving on the highway. The article focuses on developing an adaptive electronic stability controller for electric cars modelled on software Matlab-Simulink. Design a vehicle stability controller within the scope of surveying the slippage of four tyres in the stability limit ellipse corresponding to the driving angle when using a fuzzy adaptive electronic stability controller (Fuzzy-ESC) compared to compared with the electronic stability control swarm optimization controller (PSO-ESP), it minimizes skids and vehicle rollovers during obstacle avoidance, lane changing, corner entry/exit and sudden acceleration. [ABSTRACT FROM AUTHOR]

Electric power systems are undergoing rapid modernization driven by advancements in smart-grid technologies, and microgrids (MGs) play a crucial role in integrating renewable energy sources (RESs), such as wind and solar energy, into existing grids. MGs offer a flexible and efficient framework for accommodating dispersed energy resources. However, the intermittent nature of renewable sources, coupled with the rising demand for Electric Vehicles (EVs) and fast charging stations (FCSs), poses significant challenges to the stability and efficiency of microgrid (MG) operations. These challenges stem from the uncertainties in both energy generation and fluctuating demand patterns, making efficient energy management in MG a complex task. This study introduces a novel model-free strategy for real-time energy management in MG aimed at addressing uncertainties without the need for traditional uncertainty modeling techniques. Unlike conventional methods, the proposed approach enhances MG performance by minimizing power losses and operational costs. The problem is formulated as a Markov Decision Process (MDP) with well-defined objectives. To optimize decision-making, an actor-critic-based Deep Deterministic Policy Gradient (DDPG) algorithm is developed, leveraging reinforcement learning (RL) to adapt dynamically to changing system conditions. Comprehensive numerical simulations demonstrated the effectiveness of the proposed strategy. The results show a total cost of 51.8770 €ct/kWh, representing a reduction of 3.19% compared to the Dueling Deep Q Network (Dueling DQN) and 4% compared to the Deep Q Network (DQN). This highlights the robustness and scalability of the proposed model-free approach for modern MG energy management.

Abstract Background Extracellular vesicles (EVs) are a group of nanoscale cell-derived membranous structures secreted by all cell types, containing molecular cargoes involved in intercellular communication. EVs can be used to mimic “nature’s delivery system” to transport nucleic acids, peptides, lipids, and metabolites to target recipient cells. EVs offer a range of advantages over traditional synthetic carriers, thus paving the way for innovative drug delivery approaches that can be used in different diseases, including cancer. Here, by using breast cancer (BC) cells treated with the multi-kinase inhibitor sorafenib, we generated EVs enriched in specific non-coding RNAs (miR-23b-3p, miR-126-3p, and the long ncRNA GAS5) and investigated their potential impact on the aggressive properties of the BC in vitro and in vivo using zebrafish. Methods EVs were collected from 4 different BC cell lines (HCC1937, MDA-MB-231, MCF-7, and MDA-MB-453) and characterized by western blotting, transmission electron microscopy and nanoparticle tracking analysis. Levels of encapsulated miR-23b-3p, miR-126-3p, and GAS5 were quantified by ddPCR. The role of the EVs as carriers of ncRNAs in vivo was established by injecting MDA-MB-231 and MDA-MB-453 cells into zebrafish embryos followed by EV-based treatment of the xenografts with EVs rich in miR-23b-3p, miR-126-3p and GAS5. Results ddPCR analysis revealed elevated levels of miR-23b-3p, miR-126-3p, and GAS5, encapsulated in the EVs released by the aforementioned cell lines, following sorafenib treatment. The use of EVs as carriers of these specific ncRNAs in the treatment of BC cells resulted in a significant increase in the expression levels of the three ncRNAs along with the inhibition of cellular proliferation in vitro. In vivo experiments demonstrated a remarkable reduction of xenograft tumor area, suppression of angiogenesis, and decreased number of micrometastasis in the tails after administration of EVs enriched with these ncRNAs. Conclusions Our study demonstrated that sorafenib-induced EVs, enriched with specific tumor-suppressor ncRNAs, can effectively inhibit the aggressive BC characteristics in vitro and in vivo. Our findings indicate an alternative way to enrich EVs with specific tumor-suppressor ncRNAs by treating the cells with an anticancer drug and support the development of new potential experimental molecular approaches to target the aggressive properties of cancer cells.

Purpose – The demand for electric vehicles (EVs) has significantly increased in recent years, though some countries like Sri Lanka have reported the opposite direction compared to the global trend. Hence, this study focused on identifying factors affecting EV purchase intention and barriers to the widespread adoption of EVs in a developing country context. Also, this study presents an overview of the theoretical perspectives utilized for understanding consumer intentions and adoption behavior toward alternative fuel vehicles (AFVs). Design/methodology/approach – The questionnaire method was employed, and 394 individuals who lived in Colombo City, Sri Lanka, with valid driving licenses and a hybrid or conventional vehicle were the study sample. The partial least squares structural equation modeling (PLS-SEM) was used to test the research hypothesis. Findings – The findings confirmed that the three relationships between the unified theory of acceptance and use of technology (UTAUT) variables and EV purchase intention are significant, and there is no significant moderator effect from the consumer’s perceived risk. Originality/value – These results offer useful information for governments and EV companies to better understand consumer behavior toward purchasing EVs.

Abstract Last decade, extracellular vesicles (EVs) attracted a lot of attention as potent versatile drug delivery vehicles. We reported earlier the development of EV-based delivery systems for therapeutic proteins and small molecule chemotherapeutics. In this work, we first time engineered EVs with multivalent cationic lipids for the delivery of nucleic acids. Stable, small size cationized EVs were loaded with plasmid DNA (pDNA), or mRNA, or siRNA. Nucleic acid loaded EVs were efficiently taken up by target cells as demonstrated by confocal microscopy and delivered their cargo to the nuclei in triple negative breast cancer (TNBC) cells and macrophages. Efficient transfection was achieved by engineered cationized EVs formulations of pDNA- and mRNA in vitro. Furthermore, siRNA loaded into cationized EVs showed significant knockdown of the reporter gene in Luc-expressing cells. Overall, multivalent cationized EVs represent a promising strategy for gene delivery.

Abstract Background Emerging evidence has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) in chemotherapy-induced premature ovarian failure (POF). This study was designed to investigate the appropriate timing and molecular mechanism of UC-MSCs treatment for chemotherapy-induced POF. Methods Ovarian structure and function of mice were assessed every 3 days after injections with cyclophosphamide (CTX) and busulfan (BUS). UC-MSCs and UC-MSCs-derived extracellular vesicles (EVs) were infused into mice via the tail vein, respectively. Ovarian function was analyzed by follicle counts, the serum levels of hormones and ovarian morphology. The apoptosis and proliferation of ovarian granulosa cells were analyzed in vitro and in vivo. Label-free quantitative proteomics was used to detect the differentially expressed proteins in UC-MSC-derived EVs. Results After CTX/BUS injection, we observed that the ovarian function of POF mice was significantly deteriorated on day 9 after CTX/BUS infusion. TUNEL assay indicated that the number of apoptotic cells in the ovaries of POF mice was significantly higher than that in normal mice on day 3 after CTX/BUS injection. Transplantation of UC-MSCs on day 6 after CTX/BUS injection significantly improved ovarian function, enhanced proliferation and inhibited apoptosis of ovarian granulosa cells, whereas the therapeutic effect of UC-MSCs transplantation decreased on day 9, or day 12 after CTX/BUS injection. Moreover, EVs derived from UC-MSCs exerted similar therapeutic effects on POF. UC-MSCs-derived EVs could activate the PI3K/AKT signaling pathway and reduce ovarian granulosa cell apoptosis. Quantitative proteomics analysis revealed that clusterin (CLU) was highly expressed in the EVs of UC-MSCs. The supplementation of CLU proteins prevented ovarian granulosa cells from chemotherapy-induced apoptosis. Further mechanistic analysis showed that CLU-knockdown blocked the PI3K/AKT signaling and reversed the protective effects of UC-MSCs-derived EVs. Conclusions Administration of UC-MSCs and UC-MSCs-derived EVs on day 6 of CTX/BUS injection could effectively improve the ovarian function of POF mice. UC-MSCs-derived EVs carrying CLU promoted proliferation and inhibited apoptosis of ovarian granulosa cells through activating the PI3K/AKT pathway. This study identifies a previously unrecognized molecular mechanism of UC-MSCs-mediated protective effects on POF, which pave the way for the use of cell-free therapeutic approach for POF. Graphical Abstract

Abstract Background Chronic obstructive pulmonary disease (COPD) is a widespread respiratory disease. This study examines extracellular vesicles (EVs) and proteins contained in EVs in COPD. Methods Blood samples were collected from 40 COPD patients and 10 health controls. Cytokines including IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-17, were measured by ELISA. Small EVs samples were extracted from plasma and identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and Western blot. Protein components contained in EVs were analyzed by Tandem Mass Tags (TMT) to identify differential proteins. Treg-derived EV was extracted and added to isolated CD8+, Treg, and Th17 subsets to assess its effect on T-lymphocytes. Results ELISA revealed higher levels of all cytokines and flow cytometry suggested a higher proportion of Treg and Th17 cells in COPD patients. After identification, TMT analysis identified 207 unique protein components, including five potential COPD biomarkers: BTRC, TRIM28, CD209, NCOA3, and SSR3. Flow cytometry revealed that Treg-derived EVs inhibited differentiation into CD8+, CD4+, and Th17 cells. Conclusion The study shows that cytokines, T-lymphocyte subsets differences in COPD and Treg-derived EVs influence T-lymphocyte differentiation. Identified biomarkers may assist in understanding COPD pathogenesis, prognosis, and therapy. The study contributes to COPD biomarker research.

This paper presents an optimization model for the location and capacity of electric vehicle (EV) charging stations. The model takes the multiple factors of the “vehicle–station–grid” system into account. Then, ArcScene is used to couple the road and power grid models and ensure that the coupling system is strictly under the goal of minimizing the total social cost, which includes the operator cost, user charging cost, and power grid loss. An immune particle swarm optimization algorithm (IPSOA) is proposed in this paper to obtain the optimal coupling strategy. The simulation results show that the algorithm has good convergence and performs well in solving multi-modal problems. It also balances the interests of users, operators, and the power grid. Compared with other schemes, the grid loss cost is reduced by 11.1% and 17.8%, and the total social cost decreases by 9.96% and 3.22%.

Background: Extracellular vesicles (EVs) are a group of nanoscale cell-derived membranous structures secreted by all cell types, containing molecular cargoes involved in intercellular communication. EVs can be used to mimic "nature's delivery system" to transport nucleic acids, peptides, lipids, and metabolites to target recipient cells. EVs offer a range of advantages over traditional synthetic carriers, thus paving the way for innovative drug delivery approaches that can be used in different diseases, including cancer. Here, by using breast cancer (BC) cells treated with the multi-kinase inhibitor sorafenib, we generated EVs enriched in specific non-coding RNAs (miR-23b-3p, miR-126-3p, and the long ncRNA GAS5) and investigated their potential impact on the aggressive properties of the BC in vitro and in vivo using zebrafish. Methods: EVs were collected from 4 different BC cell lines (HCC1937, MDA-MB-231, MCF-7, and MDA-MB-453) and characterized by western blotting, transmission electron microscopy and nanoparticle tracking analysis. Levels of encapsulated miR-23b-3p, miR-126-3p, and GAS5 were quantified by ddPCR. The role of the EVs as carriers of ncRNAs in vivo was established by injecting MDA-MB-231 and MDA-MB-453 cells into zebrafish embryos followed by EV-based treatment of the xenografts with EVs rich in miR-23b-3p, miR-126-3p and GAS5. Results: ddPCR analysis revealed elevated levels of miR-23b-3p, miR-126-3p, and GAS5, encapsulated in the EVs released by the aforementioned cell lines, following sorafenib treatment. The use of EVs as carriers of these specific ncRNAs in the treatment of BC cells resulted in a significant increase in the expression levels of the three ncRNAs along with the inhibition of cellular proliferation in vitro. In vivo experiments demonstrated a remarkable reduction of xenograft tumor area, suppression of angiogenesis, and decreased number of micrometastasis in the tails after administration of EVs enriched with these ncRNAs. Conclusions: Our study demonstrated that sorafenib-induced EVs, enriched with specific tumor-suppressor ncRNAs, can effectively inhibit the aggressive BC characteristics in vitro and in vivo. Our findings indicate an alternative way to enrich EVs with specific tumor-suppressor ncRNAs by treating the cells with an anticancer drug and support the development of new potential experimental molecular approaches to target the aggressive properties of cancer cells. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post‐infarct cardiac regeneration. Here, we show that EVs decorated with the next‐generation of high‐affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7‐fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate‐buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nanoscale vesicles released by cells, which play an important role in intercellular communication by transporting proteins, lipids, nucleic acids, and other molecules. Different intensities of exercise can induce the release of EVs from cells and tissues, such as endothelial cells, skeletal muscle and adipose tissue, hepatocytes, immune cells, and neuronal cells. Exercise-induced EVs exert cardiovascular protective effects such as anti-inflammatory and anti-oxidative by altering their contents. This paper reviews the cell and tissue sources of EVs induced by exercise of different intensities, the regulatory effects of different exercise intensities on EVs, and their mechanisms of action in cardiovascular diseases. The aim is to provide new insights for the treatment of cardiovascular diseases and offer scientific evidence for the construction of engineered EVs mimicking the effects of exercise. [ABSTRACT FROM AUTHOR]

Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro‐ and anti‐inflammatory cytokine production and its intranasal administration reduces allergic airway inflammation in mice. Despite its benefits, there are concerns about the use of live probiotic bacteria due to potential systemic infections and gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83‐EVs) might offer a safer alternative to live bacteria. This study characterizes EcO83‐EVs and investigates their interaction with host cells, highlighting their potential as postbiotic therapeutics. EcO83‐EVs were isolated, purified, and characterised following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Ex vivo studies conducted in human nasal epithelial cells showed that EcO83‐EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83‐EVs interact with nasal‐associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. Mechanistically, EcO83‐EVs activate the NF‐κΒ signalling pathway, resulting in the nitric oxide production. EcO83‐EVs demonstrate significant potential as a postbiotic alternative to live bacteria, offering a safer option for therapeutic applications. Further research is required to explore their clinical use, particularly in mucosal vaccination and targeted immunotherapy strategies. [ABSTRACT FROM AUTHOR]

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Intelligent design has been the direction pursued by international electric vehicle (EV) research and development (R&D) teams in recent years. This paper analyzes the problems of unsustainable development in the current product design of EVs in China, such as high R&D investment, high innovation risks, and low R&D input–output ratios. It explores the issues related to intelligent design, R&D investment, car prices, and safety in the field of EVs in China, and it proposes the concept of optimizing intelligence to optimize the design investment of EVs in China. On the basis of the development situation and the existing problems of social organization standards that gather innovative technologies for EVs, this paper used data from the national social organization standard information platform as the research object and analyzed important data, such as the quantity of the information of relevant social organizations and professional fields of social organization standards, through mathematical methods. The article proposes an optimization design scheme for EV products in China, combining intelligence and practicality from the perspective of the optimizing intelligent design, and it models the construction of EV optimization design. The quantitative relationship between the two schemes before and after optimization design is compared in terms of cost savings in intelligent design, the improvement of social benefits, and the enhancement of EV cost performance. The comparative study found that intelligent optimization design reduced the R&D cost of EVs by 45.24%, and the social benefits of R&D investment increased by 29.51%. [ABSTRACT FROM AUTHOR]

Copyright of Optimum. Economic Studies is the property of University of Bialystok and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Chronic obstructive pulmonary disease (COPD) is a widespread respiratory disease. This study examines extracellular vesicles (EVs) and proteins contained in EVs in COPD. Methods: Blood samples were collected from 40 COPD patients and 10 health controls. Cytokines including IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-17, were measured by ELISA. Small EVs samples were extracted from plasma and identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and Western blot. Protein components contained in EVs were analyzed by Tandem Mass Tags (TMT) to identify differential proteins. Treg-derived EV was extracted and added to isolated CD8+, Treg, and Th17 subsets to assess its effect on T-lymphocytes. Results: ELISA revealed higher levels of all cytokines and flow cytometry suggested a higher proportion of Treg and Th17 cells in COPD patients. After identification, TMT analysis identified 207 unique protein components, including five potential COPD biomarkers: BTRC, TRIM28, CD209, NCOA3, and SSR3. Flow cytometry revealed that Treg-derived EVs inhibited differentiation into CD8+, CD4+, and Th17 cells. Conclusion: The study shows that cytokines, T-lymphocyte subsets differences in COPD and Treg-derived EVs influence T-lymphocyte differentiation. Identified biomarkers may assist in understanding COPD pathogenesis, prognosis, and therapy. The study contributes to COPD biomarker research. [ABSTRACT FROM AUTHOR]

The Indian automobile industry is witnessing a paradigm shift from fossil fuel to green energy. The current study employs an extended version of the theory of planned behaviour (TPB) to investigate the impact of attitudes, green nudges and perceived behavioural control on the behavioural intention (BI) for adoption of electric vehicles (EVs) by Indian consumers. Environmental concern is also added to the model to find its impact on actual buying behaviour (AB). Conclusive research is carried out, and data is collected through a structured questionnaire. 342 respondents were analysed using a two-step investigation approach: Partial least square-structural equation modelling (PLS-SEM), followed by an artificial neural network (ANN). Subsequently, two models are formed to determine the predictors of BI and AB. The findings suggest that all three factors positively impact BI and AB. Attitude plays the most significant role in BI (the most important predictor of AB). The study's findings also suggest that the extended TPB model is effective for forecasting customers' adoption intentions towards EVs. Moreover, this research adds to the existing literature on the intention and reluctance of consumers to embrace green technology. The results of this study will have significant implications not only for a greater understanding of customer behaviour regarding the adoption of EVs, but also for exploring their market expansion, product offerings, consumer BI and framing policies. [Display omitted] Problem Definition. • Need to understand the factors that influence consumer behavior for the adoption of Electric Vehicles (EVs). Concept. • Complexities surrounding consumer's intention and reluctance to embrace EVs implementation of carbon neutrality in organizations. Theoretical Underpinning. • An extended TPB model that includes Green Nudge & Environmental concerns. Methodology. • A hybrid PLS-SEM ANN has been used. Results. • The study validates the extended TPB model for forecasting consumer intentions towards EV adoption. Implications. • The results have significant implications for understanding consumer behavior, market expansion, product offerings, buying intentions, and policy frameworks for EV adoption. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) in chemotherapy-induced premature ovarian failure (POF). This study was designed to investigate the appropriate timing and molecular mechanism of UC-MSCs treatment for chemotherapy-induced POF. Methods: Ovarian structure and function of mice were assessed every 3 days after injections with cyclophosphamide (CTX) and busulfan (BUS). UC-MSCs and UC-MSCs-derived extracellular vesicles (EVs) were infused into mice via the tail vein, respectively. Ovarian function was analyzed by follicle counts, the serum levels of hormones and ovarian morphology. The apoptosis and proliferation of ovarian granulosa cells were analyzed in vitro and in vivo. Label-free quantitative proteomics was used to detect the differentially expressed proteins in UC-MSC-derived EVs. Results: After CTX/BUS injection, we observed that the ovarian function of POF mice was significantly deteriorated on day 9 after CTX/BUS infusion. TUNEL assay indicated that the number of apoptotic cells in the ovaries of POF mice was significantly higher than that in normal mice on day 3 after CTX/BUS injection. Transplantation of UC-MSCs on day 6 after CTX/BUS injection significantly improved ovarian function, enhanced proliferation and inhibited apoptosis of ovarian granulosa cells, whereas the therapeutic effect of UC-MSCs transplantation decreased on day 9, or day 12 after CTX/BUS injection. Moreover, EVs derived from UC-MSCs exerted similar therapeutic effects on POF. UC-MSCs-derived EVs could activate the PI3K/AKT signaling pathway and reduce ovarian granulosa cell apoptosis. Quantitative proteomics analysis revealed that clusterin (CLU) was highly expressed in the EVs of UC-MSCs. The supplementation of CLU proteins prevented ovarian granulosa cells from chemotherapy-induced apoptosis. Further mechanistic analysis showed that CLU-knockdown blocked the PI3K/AKT signaling and reversed the protective effects of UC-MSCs-derived EVs. Conclusions: Administration of UC-MSCs and UC-MSCs-derived EVs on day 6 of CTX/BUS injection could effectively improve the ovarian function of POF mice. UC-MSCs-derived EVs carrying CLU promoted proliferation and inhibited apoptosis of ovarian granulosa cells through activating the PI3K/AKT pathway. This study identifies a previously unrecognized molecular mechanism of UC-MSCs-mediated protective effects on POF, which pave the way for the use of cell-free therapeutic approach for POF. [ABSTRACT FROM AUTHOR]

Background: Transfusion‐related acute lung injury (TRALI) remains a major contributor to transfusion‐associated mortality. While the pathogenesis of TRALI remains unclear, there is evidence of a role for blood components. We therefore investigated the potential effects of fresh frozen plasma (FFP), cryoprecipitate, and extracellular vesicles (EVs) derived from these blood components, on the viability of human lung microvascular endothelial cells (HLMVECs) in vitro. Methods: EVs were isolated from FFP and cryoprecipitate using size‐exclusion chromatography and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscopy. The potential effects of these blood components and their EVs on HLMVEC viability (determined by trypan blue exclusion) were examined in the presence and absence of neutrophils, either with or without prior treatment of HLMVECs with LPS. Results: EVs isolated from FFP and cryoprecipitate displayed morphological and biochemical properties conforming to latest international criteria. While FFP, cryoprecipitate, and EVs derived from FFP, each reduced HLMVEC viability, no effect was observed for EVs derived from cryoprecipitate. Conclusion: Our findings demonstrate clear differences in the effects of FFP, cryoprecipitate, and their respective EVs on HLMVEC viability in vitro. Examination of the mechanisms underlying these differences may lead to an improved understanding of the factors that promote development of TRALI. [ABSTRACT FROM AUTHOR]

The high mortality in the global population due to chronic diseases highlights the urgency to identify effective alternative therapies. Regenerative medicine provides promising new approaches for this purpose, particularly in the use of induced pluripotent stem cells (iPSCs). The aim of the work is to establish a new pluripotency cell line obtained for the first time by reprogramming human gingival mesenchymal stem cells (hGMSCs) by a non-integrating method. The hGMSC-derived iPS line characterization is performed through morphological analysis with optical and electron scanning microscopy and through the pluripotency markers expression evaluation in cytofluorimetry, immunofluorescence, and RT-PCR. To confirm the pluripotency of new hGMSC-derived iPS, the formation of embryoid bodies (EBs), as an alternative to the teratoma formation test, is studied in morphological analysis and through three germ layers' markers' expression in immunofluorescence and RT-PCR. At the end, a comparative study between parental hGMSCs and derived iPS cells is performed also for the extracellular vesicles (EVs) and their miRNA content. The new hGMSC-derived iPS line demonstrated to be pluripotent in all aspects, thus representing an innovative dynamic platform for personalized tissue regeneration. [ABSTRACT FROM AUTHOR]

Breakthroughs in surgical and medical techniques have significantly improved outcomes for children with congenital heart disease (CHD), but research continues to address the ongoing challenge of organ dysfunction after surgery, particularly in neonates and infants. Our study explored circular RNAs (circRNAs) within plasma-derived extracellular vesicles (EVs) in neonates and infants undergoing CHD surgery. Post-surgery EV circRNAs showed dramatic expression changes between organ dysfunction (OD) and control groups. Tissue injury-related pathways were consistent across pre- and post-surgery in OD. The top two significant predicted tissue sources of these circRNAs originated from the respiratory system, aligning with the fact that all patients in the OD arm experienced respiratory dysfunction. Five of these circRNAs, namely circ-CELSR1, circ-PLXNA1, circ-OBSL1, circ-DAB2IP, and circ-KANK1, significantly correlated with PELOD (Pediatric Logistic Organ Dysfunction) score and demonstrated high performance (AUC = 0.95), supporting the potential of circRNAs as prognostic markers. These findings pave the way for EV circRNAs as promising tools for managing post-surgical organ dysfunction and potentially guiding therapeutic strategies in children with CHD. [ABSTRACT FROM AUTHOR]

This review provides a concise history of road transport vehicles and analyzes the environmental problems caused by them. Many issues have arisen as a result of modern transportation, such as air pollution, global warming, and the depletion of fossil fuels. The article covers the current and future electric vehicle needs of key nations. It explains various types of electric vehicles and discusses several configurations of Hybrid Electric Vehicles (HEVs), including series, parallel, series-parallel, torque-coupling, and speed-coupling systems, and how they function. The article concludes by discussing potential future prospects for engineers and the electric vehicle industry. [ABSTRACT FROM AUTHOR]