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Battery Management System (BMS) functions to monitor individual cell in a battery pack and its crucial task is to maintain stability throughout the battery pack. The BMS is responsible for maintaining the safety of the battery as well as not to harm the user or environment. The parameters that are to be monitored in a battery are Voltage, Current and Temperature. With the collected data, BMS carefully monitors the charging–discharging behavior of the battery particularly in the Lithium-ion (Li-ion) batteries in which charging and discharging behavior are completely different. This paper proposes a real-time IOT connected deep learning algorithm for estimation of State-of-Charge (SoC) of Li-ion batteries. This paper provides unique objectives and congruence between model-based conventional methods and state-of-the-art deep learning algorithm, specifically Feed Forward Neural Network (FNN) which is nonRecurrent. This paper also highlights the advantages of Internet-of-Things (IoT) connected deep learning algorithm for estimation of State-of-Charge of Li-ion batteries in Hybrid Electric Vehicles (HEVs) and Electric Vehicles (EVs). The major advantage of the proposed method is that the Artificial Intelligence (AI)-based techniques aim to bring the estimation error less than 2% at a low cost and time without the model of the battery, at par with conventional method of Extended Kalman Filter (EKF) which is the best ever practical estimation theory. Another advantage of the proposed method is that in an abnormal condition (i.e., Unsafe Temperature) the IF This Then That (IFTTT) IoT mobile application interfaced with BMS through ThingSpeak cloud, sends a notification alert to the battery expert or to the user prior to an emergency. Finally, the real-time data of the battery parameters are collected through ThingSpeak cloud platform for future research and analysis. [ABSTRACT FROM AUTHOR]

The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential. [ABSTRACT FROM AUTHOR]

We have demonstrated that directly reprogramming cardiac fibroblasts into new cardiomyocytes via miR combo improves cardiac function in the infarcted heart. However, major challenges exist with delivery and efficacy. During a screening based approach to improve delivery, we discovered that C166-derived EVs were effective delivery agents for miR combo both in vitro and in vivo. In the latter, EV mediated delivery of miR combo induced significant conversion of cardiac fibroblasts into cardiomyocytes (∼20%), reduced fibrosis and improved cardiac function in a myocardial infarction injury model. When compared to lipid-based transfection, C166 EV mediated delivery of miR combo enhanced reprogramming efficacy. Improved reprogramming efficacy was found to result from a miRNA within the exosome: miR-148a-3p. The target of miR-148a-3p was identified as Mdfic. Over-expression and targeted knockdown studies demonstrated that Mdfic was a repressor of cardiomyocyte specific gene expression. In conclusion, we have demonstrated that C166-derived EVs are an effective method for delivering reprogramming factors to cardiac fibroblasts and we have identified a novel miRNA contained within C166-derived EVs which enhances reprogramming efficacy. [Display omitted] • Reprogramming scar cells into cardiac muscle improves function in infarcted heart. • Issues with delivery and lack of mechanisms impacts reprogramming effectiveness. • C166-derived EVs target scar cells and effectively deliver reprogramming factors. • miR-148a-3p improves reprogramming efficacy by targeting Mdfic. [ABSTRACT FROM AUTHOR]

Kidney fibrosis is a common outcome of a wide variety of chronic kidney diseases, in which virtually all kinds of renal resident and infiltrating cells are involved. As such, well-orchestrated intercellular communication is of vital importance in coordinating complex actions during renal fibrogenesis. Cell–cell communication in multicellular organisms is traditionally assumed to be mediated by direct cell contact or soluble factors, including growth factors, cytokines and chemokines, through autocrine, paracrine, endocrine and juxtacrine signaling mechanisms. Growing evidence also demonstrates that extracellular vesicles, lipid bilayer–encircled particles naturally released from almost all types of cells, can act as a vehicle to transfer a diverse array of biomolecules including proteins, mRNA, miRNA and lipids to mediate cell–cell communication. We recently described a new mode of intercellular communication via building a special extracellular niche by insoluble matricellular proteins. Kidney cells, upon injury, produce and secrete different matricellular proteins, which incorporate into the local extracellular matrix network, and regulate the behavior, trajectory and fate of neighboring cells in a spatially confined fashion. This extracellular niche–mediated cell–cell communication is unique in that it restrains the crosstalk between cells within a particular locality. Detailed delineation of this unique manner of intercellular communication will help to elucidate the mechanism of kidney fibrosis and could offer novel insights in developing therapeutic intervention. [ABSTRACT FROM AUTHOR]

Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy. Fibrinogen-like protein-1 (FGL1) was overexpressed in lung adenocarcinoma and could be secreted via extracellular vesicles (EVs). FGL1 on plasma EVs, not total plasma FGL1, is correlated with clinical TNM(Tumor Node Metastasis)staging and non-responsiveness to anti-programmed cell death ligand 1 therapy, which could be a new potential target for immunotherapy Graphical Abstract [ABSTRACT FROM AUTHOR]

The rapid increase in electric vehicles (EVs) has led to a continuous expansion of electric vehicle (EV) charging stations, imposing significant load pressures on the power grid. Implementing orderly charging scheduling for EVs can mitigate the impact of large-scale charging on the power grid. However, the charging behavior of EVs significantly impacts the efficiency of orderly charging plans. By integrating user portrait technology and conducting research on optimized scheduling for EV charging, EV users can be accurately classified to meet the diverse needs of various user groups. This study establishes a user portrait model suitable for park areas, providing user group classification based on the user response potential for scheduling optimization. First, the FCM and feature aggregation methods are utilized to classify the quantities of features of EV users, obtaining user portrait classes. Second, based on these classes, a user portrait inventory for each EV is derived. Third, based on the priority of user response potential, this study presents a method for calculating the feature data of different user groups. The individual data information and priorities from the user portrait model are inputted into the EV-optimized scheduling model. The optimization focuses on the user charging cost and load fluctuation, with the non-dominated sorting genetic algorithm II utilized to obtain the solutions. The results demonstrate that the proposed strategy effectively addresses the matching issue between the EV user response potential and optimal scheduling modes without compromising the normal use of EVs by users. This classification approach facilitates the easier acceptance of scheduling tasks by participating users, leading to optimized outcomes that better meet practical requirements. [ABSTRACT FROM AUTHOR]

Global warming, pollution, and increasing energy demand have compelled electrification of the transport sector. Electric vehicles are not only an attractive and cleaner mode of transport, but they also possess the capacity to offer flexible storage alternative based on bidirectional vehicle-to-grid schemes. Vehicle-to-grid or V2G technology permits electric vehicles' batteries to store energy and discharge it back to the power grid during peak-load periods. However, the feasibility and economic viability of V2G is still a matter of concern and needs investigation. In this paper, the authors delved into the feasibility of V2G technology by analysing the real time-charging data of a V2G demonstration project named EV-elocity, located at the University of Nottingham campus in the UK. The authors analysed the charging data and trip-status data of two charging sites and put forward some insights regarding the feasibility of V2G and the behavioural traits of the vehicles. This paper will enlighten the research community regarding the feasibility and benefits of V2G in a real-world environment by analysing the charging/discharging and vehicle behaviour and reporting the opportunities and benefits of vehicle-to-grid technology. [ABSTRACT FROM AUTHOR]

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1β). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, it is described that embryos produced in vitro release nanoparticles charged with fragments of embryonic DNA. These nanoparticles, alongside their DNA content, can be recovered from the liquid medium where the embryos develop in vitro and used to assess the genetics of embryos. The analysis of gene markers is a common practice in clinics for selecting human embryos without genomic errors. In animals, it can help in selecting embryos with high genetic value. So far, this has been achieved using embryonic biopsy to collect several cells; however, this is invasive due to the manipulation of the embryo. In this sense, the secreted nanoparticles containing DNA could stand as samples for genetic analysis, without disturbing the embryo. The main concern is whether these particles are mainly released by low-quality embryos that will eventually die. This work aimed to evaluate whether the rate of cell death in the embryo affects the release of particles containing DNA. It was confirmed that viable and good-quality embryos secrete particles with DNA in the same way as low-quality embryos; therefore, they represent a suitable alternative for embryonic genetic diagnosis, avoiding the invasive nature and technical complexity of a biopsy. Pre-implantation embryos release extracellular vesicles containing different molecules, including DNA. The presence of embryonic DNA in E-EVs released into the culture medium during in vitro embryo production could be useful for genetic diagnosis. However, the vesicles containing DNA might be derived from embryos suffering from apoptosis, i.e., embryos of bad quality. This work intended to confirm that embryos release DNA that is useful for genotyping by evaluating the effect of embryonic apoptosis on DNA content in E-EVs. Bovine embryos were produced by parthenogenesis and in vitro fertilization (IVF). On Day 5, morulae were transferred to individual cultures in an EV-depleted SOF medium. On Day 7, embryos were used to evaluate cellular apoptosis, and each culture medium was collected to evaluate E-EV concentration, characterization, and DNA quantification. While no effect of the origin of the embryo on the apoptotic rate was found, arrested morulae had a higher apoptotic rate. E-EVs containing DNA were identified in all samples, and the concentration of those vesicles was not affected by the origin or quality of the embryos. However, the concentration of DNA was higher in EVs released by the arrested parthenogenetic embryos. There was a correlation between the concentration of E-EVs, the concentration of DNA-positive E-EVs, and the concentration of DNA. There was no negative effect of apoptotic rate on DNA-positive E-EVs and DNA concentration; however, embryos of the best quality with a low apoptotic rate still released EVs containing DNA. This study confirms that the presence of DNA in E-EVs is independent of embryo quality. Therefore, E-EVs could be used in liquid biopsy for noninvasive genetic diagnosis. [ABSTRACT FROM AUTHOR]

Small Extracellular Vesicles (sEVs) are typically 30–150 nm in diameter, produced inside cells, and released into the extracellular space. These vesicles carry RNA, DNA, proteins, and lipids that reflect the characteristics of their parent cells, enabling communication between cells and the alteration of functions or differentiation of target cells. Owing to these properties, sEVs have recently gained attention as potential carriers for functional molecules and drug delivery tools. However, their use as a therapeutic platform faces limitations, such as challenges in mass production, purity issues, and the absence of established protocols and characterization methods. To overcome these, researchers are exploring the characterization and engineering of sEVs for various applications. This review discusses the origins of sEVs and their engineering for therapeutic effects, proposing areas needing intensive study. It covers the use of cell-derived sEVs in their natural state and in engineered forms for specific purposes. Additionally, the review details the sources of sEVs and their subsequent purification methods. It also outlines the potential of therapeutic sEVs and the requirements for successful clinical trials, including methods for large-scale production and purification. Finally, we discuss the progress of ongoing clinical trials and the implications for future healthcare, offering a comprehensive overview of the latest research in sEV applications. [ABSTRACT FROM AUTHOR]

This study explores the rheological and tribological behavior of water-based lubricants (WBLs) as potential alternatives for electric vehicle (EV) applications. As the transportation sector increasingly shifts towards EVs to reduce carbon emissions, the demand for efficient lubricants becomes critical. WBLs here are defined as fluids containing a minimum of 50 wt% water mixed with glycerol, ethylene glycol (MEG), polyethylene glycol (PEG), or one of two polyalkylene glycols (PAGs). Rheological properties were investigated and compared with traditional lubricating oils. Results demonstrate distinctive rheological characteristics in WBLs, with viscosity–temperature responses resembling traditional oils with lowered pressure–viscosity coefficients. Nevertheless, WBLs exhibit promising film-forming capabilities in highly loaded contacts. Additionally, in sliding contacts, WBLs generally display lower friction coefficients compared to traditional oils, with PEG exhibiting the lowest value near 0.1. These findings suggest that WBLs may offer advantages in reducing friction and energy loss in EV applications. Furthermore, sliding wear tests indicate low wear rates in WBLs such as PEG, PAG, and glycerol, supporting their potential as viable lubrication options. The study highlights the importance of high-pressure rheology and tribochemistry in wear mechanisms among the different lubricants. [ABSTRACT FROM AUTHOR]

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP‐ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV‐marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP‐ALL patients. The EV proteome of primary BCP‐ALL cell‐derived EVs were compared against EVs from healthy donor B cells and the BCP‐ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP‐ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP‐ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri‐implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing "remarkable" potential, serving as a valuable tool for clinicians with significant advantages. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second most prevalent cancer type worldwide, which highlights the urgent need for non-invasive biomarkers for its early detection and improved prognosis. We aimed to investigate the patterns of long non-coding RNAs (lncRNAs) in small extracellular vesicles (sEVs) collected from low-volume blood serum specimens of CRC patients, focusing on their potential as diagnostic biomarkers. Our research comprised two phases: an initial exploratory phase involving RNA sequencing of sEVs from 76 CRC patients and 29 healthy controls, and a subsequent validation phase with a larger cohort of 159 CRC patients and 138 healthy controls. Techniques such as dynamic light scattering, transmission electron microscopy, and Western blotting were utilized for sEV characterization. Optimized protocol for sEV purification, RNA isolation and preamplification was applied to successfully sequence the RNA content of sEVs and validate the results by RT-qPCR. We successfully isolated sEVs from blood serum and prepared sequencing libraries from a low amount of RNA. High-throughput sequencing identified differential levels of 460 transcripts between CRC patients and healthy controls, including mRNAs, lncRNAs, and pseudogenes, with approximately 20% being lncRNAs, highlighting several tumor-specific lncRNAs that have not been associated with CRC development and progression. The validation phase confirmed the upregulation of three lncRNAs (NALT1, AL096828, and LINC01637) in blood serum of CRC patients. This study not only identified lncRNA profiles in a population of sEVs from low-volume blood serum specimens of CRC patients but also highlights the value of innovative techniques in biomolecular research, particularly for the detection and analysis of low-abundance biomolecules in clinical samples. The identification of specific lncRNAs associated with CRC provides a foundation for future research into their functional roles in cancer development and potential clinical applications. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) in biofluids are highly heterogeneous entities in terms of their origins and physicochemical properties. Considering the application of EVs in diagnostic and therapeutic fields, it is of extreme importance to establish differentiating methods by which focused EV subclasses are operationally defined. Several differentiation protocols have been proposed; however, they have mainly focused on smaller types of EVs, and the heterogeneous nature of large EVs has not yet been fully explored. In this report, to classify large EVs into subgroups based on their physicochemical properties, we have developed a protocol, named EV differentiation by sedimentation patterns (ESP), in which entities in the crude large EV fraction are first moved through a density gradient of iodixanol with small centrifugation forces, and then the migration patterns of molecules through the gradients are analysed using a non‐hierarchical data clustering algorithm. Based on this method, proteins in the large EV fractions of oral fluids clustered into three groups: proteins shared with small EV cargos and enriched in immuno‐related proteins (Group 1), proteins involved in energy metabolism and protein synthesis (Group 2), and proteins required for vesicle trafficking (Group 3). These observations indicate that the physiochemical properties of EVs, which are defined through low‐speed gradient centrifugation, are well associated with their functions within cells. This protocol enables the detailed subclassification of EV populations that are difficult to differentiate using conventional separation methods. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further study the role of EVs, we have analysed by Raman tweezers microspectroscopy and mass spectrometry‐based lipidomics the small EVs population secreted by fatty (ZF) and lean (ZL) hepatocytes obtained from Zucker rats. We have also explored in vivo and ex vivo biodistribution of these EVs through fluorine‐18‐radiolabelling using a positron emission tomography imaging. Based on the proportion of proteins to lipids and the types of lipids, our results indicate that within the range of small EVs, primary hepatocytes secrete different subpopulations of particles. These differences were observed in the enrichment of triglyceride species in EVs secreted by ZF hepatocytes. Biodistribution experiments showed accumulation in the brain, heart, lungs, kidney and specially in bladder after intravenous administration. In summary, we show that EVs released by a fatty hepatocytes carry a different lipid signature compared to their lean counterpart. Biodistribution experiment has shown no difference in the distribution of EVs secreted by ZF and ZL hepatocytes but has given us a first view of possible target organs for these particles. Our results might open a door to both pathology studies and therapeutic interventions. [ABSTRACT FROM AUTHOR]

This study proposes a simulation technique for investigating a battery thermal management system based on direct refrigerant cooling (BTMS-DRC). The main focus is to investigate the temperature uniformity and working temperature of the module housing. The simulation technique employs a finite element method for a combined conduction–convection heat transfer to predict the module housing temperature. The refrigerant side is based on two-phase flow evaporation, which is represented by the convection heat transfer under a certain refrigerant saturation temperature. The real BTMS-DRC, which is based on the dual-evaporator vapor compression refrigeration system, is constructed for experimentation with the test bench. The simulated result is validated with the experimental results to ensure correction of the modelling. Error rates of approximately 2.9–7.2% are noted throughout the specified working conditions. The BTMS can produce temperatures of less than 35 °C under conditions where 80–320 W heat is generated. The difference in the temperature of the module is around 1.7–4.2 °C. This study also investigates the impact of heat generation, the convection heat transfer coefficient (href), the refrigerant saturation temperature, and thermal conductivity on the module's temperature. The thermal conductivity ranges from 25 to 430 W/m·K, while the href ranges from 80 to 400 W/m2·K. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and, with increasing research on the tumor immune microenvironment (TIME), the immunosuppressive micro-environment of HCC hampers further application of immunotherapy, even though immunotherapy can provide survival benefits to patients with advanced liver cancer. Current studies suggest that polyamine metabolism is not only a key metabolic pathway for the formation of immunosuppressive phenotypes in tumor-associated macrophages (TAMs), but it is also profoundly involved in mitochondrial quality control signaling and the energy metabolism regulation process, so it is particularly important to further investigate the role of polyamine metabolism in the tumor microenvironment (TME). In this review, by summarizing the current research progress of key enzymes and substrates of the polyamine metabolic pathway in regulating TAMs and T cells, we propose that polyamine biosynthesis can intervene in the process of mitochondrial energy metabolism by affecting mitochondrial autophagy, which, in turn, regulates macrophage polarization and T cell differentiation. Polyamine metabolism may be a key target for the interactive dialog between HCC cells and immune cells such as TAMs, so interfering with polyamine metabolism may become an important entry point to break intercellular communication, providing new research space for developing polyamine metabolism-based therapy for HCC. [ABSTRACT FROM AUTHOR]

A novel Loop Heat Pipe (LHP) is developed as passive cooling system for Battery Thermal Management System (BTMS). LHPs are more efficient than traditional heat pipes at transferring heat at larger distances, which is essential for keeping the batteries in a safe and efficient temperature range. The Single Evaporator Loop Heat Pipe (SE-LHP) BTMS is tested on a battery module comprising of twelve 18,650 lithium-ion battery cells. The tests are conducted at various charge and discharge rates (1C, 1.5C, and 2C) and ambient temperatures ranging from 30°C to 45°C. The SE-LHP BTMS significantly reduces the maximum cell temperature compared to a module without BTMS. At an ambient temperature of 35°C, the SE-LHP BTMS attains temperature drops of 15%, 16.4%, and 16.29% during battery charge rates of 1C, 1.5C, and 2C, respectively. The SE-LHP BTMS also increases the discharge capacity of the battery module. For the 1.5C discharge rate, the discharge capacity increases from 41% State of Charge (SOC) to 0% SOC with the SE-LHP BTMS, compared to 39% SOC without BTMS. For the 2C discharge rate, the discharge capacity increases from 59% SOC to 0% SOC with the SE-LHP BTMS, compared to 56% SOC without BTMS. The SE-LHP BTMS also helps to keep even temperature spreading among the battery cells. When the module is exposed to ambient temperatures ranging from 30°C to 45°C, the SE-LHP BTMS keeps a temperature difference of less than 2.43°C and 3.38°C among the battery cells for all charge and discharge rates, respectively. [ABSTRACT FROM AUTHOR]

Background: During kidney organogenesis, metanephric mesenchyme (MM) and ureteric bud (UB) interact reciprocally to form nephrons. Signaling stimuli involved in these interactions include Wnts, growth factors and nano/micro particles. How UB and MM are interacting is not completely understood. Our study investigated the signaling and communication via extracellular vesicles (EVs) during nephrogenesis. Embryonic day (E) 11.5 mouse kidney UB and MM produce very low number of primary cells that have limited ability for proliferation in culture. Such limitations obstruct studying the role of EVs in induction of nephrogenesis. These issues necessitate to generate a nephrogenesis model allowing to study the comprehensive role of EVs during nephrogenesis. Results: Our study generated a UB derived cell line-based in vitro flexible model of nephrogenesis allowing expandable cell culturing, in addition to performing characterization, tracking and blocking of EVs. UB cell line aggregation with E11.5 MM cells induced the formation of segmented nephrons. Most efficient nephrogenesis was obtained by the co-culturing of 30,000 cells of UB cell line with 50,000 MM cells. Results revealed that both the UB and the MM secrete EVs during nephrogenesis. UB cell line derived EVs were characterized by their size, morphology and expression of markers (CD63, TSG101, CD9 and CD81). Furthermore, proteomics data of UB cell line-derived EVs revealed large number of proteins involved in nephrogenesis-related signaling pathways. Palmitoylated GFP-tagged EVs from UB cell line were found in the nephron formation zone in the developing kidney organoid. UB cell line derived EVs did not induce nephrogenesis in MM cells but significantly contributed to the survival and nephrogenesis-competency of MM cells. The secretion of EVs was continuously inhibited during the ongoing nephrogenesis by the knockdown of RalA and RalB gene expression using short hairpin RNAs. This inhibition partially impaired the ability of UB cell line to induce nephrogenesis. Moreover, impaired nephrogenesis was partially rescued by the addition of EVs. Conclusion: Our study established a novel in vitro flexible model of nephrogenesis that solved the limitations of primary embryonic kidney cells and mouse embryonic stem cell kidney organoids for the EV research. EVs were found to be an integral part of nephrogenesis process. 7F9YfcJgNbSGEsBfhqoDc7 Video Abstract [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are lipid membrane-bound particles involved in cell-to-cell communication through a delivery of regulatory molecules essential for physiological processes. Since EVs efficiently vectorize specific cargo molecules, they have been proposed as suitable vehicles for therapeutic agents. Drug loading into EVs can be achieved by active, exogenous strategies or by genetic modifications of vesicle-producing cells. With the aim to produce EVs conveying therapeutic proteins, we genetically engineered and compared HEK293 to tumor cells. Tetraspanin-based RFP fusions were found to be more stable and preferentially sorted into EVs in HEK293. EVs isolated from genetically modified HEK293 cells media were captured by cancer cells, efficiently delivering their cargo. Cathepsin B cleavage site introduced between CD9/CD81 and RFP was recognized by tumor specific proteases allowing the release of the reporter protein. Our results indicate HEK293 cells as a preferential system for the production of EVs and pave the way to the development of nano-platforms for the efficient delivery of therapeutic proteins and prodrugs to tumor cells. [ABSTRACT FROM AUTHOR]

Suicide is an important public‐health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long‐distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR‐16‐5p, miR‐19a‐3p, miR‐34c‐5p, miR‐17‐5p, miR‐4286, miR‐26b‐5p, miR‐381‐3p, and miR‐4516) miR‐19a‐3p and miR‐4516 reached statistical significance with p‐values of 0.0408 and 0.0168, respectively. Mir‐4516 and miRNA‐19a‐3p have been previously studied in suicide, and target SLC6A4 and TNF‐α expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential. [ABSTRACT FROM AUTHOR]

Lung infections are one of the most common causes of death and morbidity worldwide. Both bacterial and viral lung infections cause a vast number of infections with varying severities. Extracellular vesicles (EVs) produced by different cells due to infection in the lung have the ability to modify the immune system, leading to either better immune response or worsening of the disease. It has been shown that both bacteria and viruses have the ability to produce their EVs and stimulate the immune system for that. In this review, we investigate topics from EV biogenesis and types of EVs to lung bacterial and viral infections caused by various bacterial species. Mycobacterium tuberculosis, Staphylococcus aureus, and Streptococcus pneumoniae infections are covered intensively in this review. Moreover, various viral lung infections, including SARS-CoV-2 infections, have been depicted extensively. In this review, we focus on eukaryotic-cell-derived EVs as an important component of disease pathogenesis. Finally, this review holds high novelty in its findings and literature review. It represents the first time to cover all different information on immune-cell-derived EVs in both bacterial and viral lung infections. [ABSTRACT FROM AUTHOR]

Non-healing wound- and tissue-injury are commonly experienced worldwide by the aging population. The persistence of disease commonly leads to tissue infection, resulting in severe clinical complications. In the last decade, extracellular vesicles (EVs) have been considered promising and emergent therapeutic tools to improve the healing processes. Therefore, efforts have been directed to develop a cell-free therapeutic platform based on EV administration to orchestrate tissue repair. EVs derived from different cell types, including fibroblast, epithelial, and immune cells are recruited to the injured sites and in turn take part in scar formation. EVs are nano-sized particles containing a heterogeneous cargo consisting of lipids, proteins, and nucleic acids protected from degradation by their lipid bilayer. Noteworthy, since EVs have natural biocompatibility and low immunogenicity, they represent the ideal therapeutic candidates for regenerative purposes. Indeed, EVs are released by several cell types, and even if they possess unique biological properties, their functional capability can be further improved by engineering their content and functionalizing their surface, allowing a specific cell cargo delivery. Herein, we provide an overview of preclinical data supporting the contribution of EVs in the repair and regenerative processes, focusing on different naïve EV sources, as well as on their engineering, to offer a scalable and low-cost therapeutic option for tissue repair. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and progressive dementia. Midlife obesity increases the risk of developing AD. Adipocyte-derived small extracellular vesicles (ad-sEVs) have been implicated as a mechanism in several obesity-related diseases. We hypothesized that ad-sEVs from patients with AD would contain miRNAs predicted to downregulate pathways involved in synaptic plasticity and memory formation. We isolated ad-sEVs from the serum and cerebrospinal fluid (CSF) of patients with AD and controls and compared miRNA expression profiles. We performed weighted gene co-expression network analysis (WGCNA) on differentially expressed miRNAs to identify highly interconnected clusters correlating with clinical traits. The WGCNA identified a module of differentially expressed miRNAs, in both the serum and CSF, that was inversely correlated with the Mini-Mental State Examination scores. Within this module, miRNAs that downregulate CREB signaling in neurons were highly represented. These results demonstrate that miRNAs carried by ad-sEVs in patients with AD may downregulate CREB signaling and provide a potential mechanistic link between midlife obesity and increased risk of AD. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, we show that Tregs maintain the tolerogenic state of the testis and epididymis, where sperm are produced and mature. We found that Treg depletion induces severe autoimmune orchitis and epididymitis, manifested by an exacerbated immune cell infiltration [CD4 T cells, monocytes, and mononuclear phagocytes (MPs)] and the development of antisperm antibodies (ASA). In Treg-depleted mice, MPs increased projections toward the epididymal lumen as well as invading the lumen. ASA-bound sperm enhance sperm agglutination and might facilitate sperm phagocytosis. Tolerance breakdown impaired epididymal epithelial function and altered extracellular vesicle cargo, both of which play crucial roles in the acquisition of sperm fertilizing ability and subsequent embryo development. The affected mice had reduced sperm number and motility and severe fertility defects. Deciphering these immunoregulatory mechanisms may help to design new strategies to treat male infertility, as well as to identify potential targets for immunocontraception. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is an irreversible and fatal lung disease that is primarily found in the elderly population, and several studies have demonstrated that aging is the major risk factor for IPF. IPF is characterized by the presence of apoptosis-resistant, senescent fibroblasts that generate an excessively stiff extracellular matrix (ECM). The ECM profoundly affects cellular functions and tissue homeostasis, and an aberrant ECM is closely associated with the development of lung fibrosis. Aging progressively alters ECM components and is associated with the accumulation of senescent cells that promote age-related tissue dysfunction through the expression of factors linked to a senescence-associated secretary phenotype (SASP). There is growing evidence that SASP factors affect various cell behaviors and influence ECM turnover in lung tissue through autocrine and/or paracrine signaling mechanisms. Since life expectancy is increasing worldwide, it is important to elucidate how aging affects ECM dynamics and turnover via SASP and thereby promotes lung fibrosis. In this review, we will focus on the molecular properties of SASP and its regulatory mechanisms. Furthermore, the pathophysiological process of ECM remodeling by SASP factors and the influence of an altered ECM from aged lungs on the development of lung fibrosis will be highlighted. Finally, recent attempts to target ECM alteration and senescent cells to modulate fibrosis will be introduced. [ABSTRACT FROM AUTHOR]

The herpetofauna of the insular systems of Mexico is composed of 226 species, of which 14 are anurans, two are salamanders, and 210 are reptiles, comprised of two crocodilians, 195 squamates, and 13 turtles. Although the surface of the Mexican islands is only 0.26% of the Mexican territorial extension, these 226 species constitute 16.1% of Mexico's documented herpetofauna of 1405 species. We classified the Mexican islands into five physiographic regions: the islands of Pacific Baja California; the islands of the Gulf of California; the islands of the Tropical Pacific; the islands of the Gulf of Mexico; and the islands of the Mexican Caribbean. The highest species richness among these regions is in the Gulf of California, with 108 species, and the lowest richness is 40 for the islands of the Pacific Baja California and 46 for those of the Gulf of Mexico. We identified introduced species, risk of wildfires, climate change, and urban/tourist development as the main environmental threats impinging on these species. In addition, we assessed the conservation status of the native species by comparing the SEMARNAT (NOM-059), IUCN Red List, and the Environmental Vulnerability Score (EVS) systems. The comparison of these systems showed that the NOM-059 and the IUCN systems seriously underestimate the degree of threat for insular endemics, being particularly concerning for those insular species that are known only from their respective type localities. The EVS system proved to be practical and indicated that 94 species have a high vulnerability status, 62 a medium status, and 56 a low status. The Relative Herpetofaunal Priority system, which contrasts the number of endemic and threatened species among different physiographic areas, indicates that the regions with the highest priority are the Islands of the Gulf of California, followed by the islands of the Tropical Pacific. Finally, we discussed the completeness of the Mexican Natural Protected Areas on the insular systems of the country; the result is outstanding since Mexico is already close to achieving the goal of having all their islands under some degree of federal protection. [ABSTRACT FROM AUTHOR]

Currently, there is no cure for human immunodeficiency virus type 1 (HIV-1) infection. However, combined antiretroviral therapy (cART) aids in viral latency and prevents the progression of HIV-1 infection into acquired immunodeficiency syndrome (AIDS). cART has extended many lives, but people living with HIV-1 (PLWH) face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) that range from asymptomatic HAND to HIV-1-associated dementia. HAND has been attributed to chronic inflammation and low-level infection within the central nervous system (CNS) caused by proinflammatory cytokines and viral products. These molecules are shuttled into the CNS within extracellular vesicles (EVs), lipid bound nanoparticles, and are released from cells as a form of intercellular communication. This study investigates the impact of cannabidiol (CBD), as a promising and potential therapeutic for HAND patients, and a similar synthetic molecule, HU308, on the EVs released from HIV-1-infected myeloid cells as well as HIV-1-infected 3D neurospheres. The data shows that both CBD and HU308 decrease non-coding and coding viral RNA (TAR and env) as well as proinflammatory cytokines as IL-1β and TNF-α mRNA. This decrease in viral RNA occurs in in vitro differentiated primary macrophages, in EVs released from HIV-1-infected cells monocytes, and infected neurospheres. Furthermore, a 3D neurosphere model shows an overall decrease in proinflammatory mRNA with HU308. Finally, using a humanized mouse model of HIV-1 infection, plasma viral RNA was shown to significantly decrease with HU308 alone and was most effective in combination with cART, even when compared to the typical cART treatment. Overall, CBD or HU308 may be a viable option to decrease EV release and associated cytokines which would dampen the virus spread and may be used in effective treatment of HAND in combination with cART. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries (LIBs) are widely used in electrical vehicles (EVs), but safety issues with LIBs still occur frequently. State of charge (SOC) and state of health (SOH) are two crucial parameters for describing the state of LIBs. However, due to inconsistencies that may occur among hundreds to thousands of battery cells connected in series and parallel in the battery pack, these parameters can be difficult to estimate accurately. To address this problem, this paper proposes a joint SOC and SOH estimation method based on the nonlinear state space reconstruction (NSSR) and long short-term memory (LSTM) neural network. An experiment testbed was set up to measure the SOC and SOH of battery packs under different criteria and configurations, and thousands of charging/discharging cycles were recorded. The joint estimation algorithms were validated using testbed data, and the errors for SOC and SOH estimation were found to be within 2.5% and 1.3%, respectively, which is smaller than the errors obtained using traditional Ah-Integral and LSTM-only algorithms. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nanoparticles containing various bioactive cargos—e.g., proteins, RNAs, and lipids—that are released into the environment by all cell types. They are involved in, amongst other functions, intercellular communication. This article presents studies on EVs produced by the probiotic yeast Saccharomyces boulardii CNCM I-745. The size distribution and concentration of EVs in the liquid culture of yeast were estimated. Moreover, the vesicles of S. boulardii were tested for their cytotoxicity against three model human intestinal cell lines. This study did not show any significant negative effect of yeast EVs on these cells under tested conditions. In addition, EVs of S. boulardii were verified for their ability to internalize in vitro with human cells and transfer their cargo. The yeast vesicles were loaded with doxorubicin, an anticancer agent, and added to the cellular cultures. Subsequently, microscopic observations revealed that these EVs transferred the compound to human intestinal cell lines. A cytotoxicity test confirmed the activity of the transferred doxorubicin. Detailed information about the proteins present in EVs might be important in terms of exploring yeast EVs as carriers of active molecules. Thus, proteomic analysis of the EV content was also conducted within the present study, and it allowed the identification of 541 proteins after matching them to the Saccharomyces Genome Database (SGD). Altogether, this study provides strong evidence that the EVs of the probiotic CNCM I-745 strain could be considered a drug delivery system. [ABSTRACT FROM AUTHOR]

Recent evidence has shown significant roles of mitochondria-derived vesicles (MDVs) in mitochondrial quality control (MQC) system. Under mild stress condition, MDVs are formed to carry the malfunctioned mitochondrial components, such as mitochondrial DNA (mtDNA), peptides, proteins and lipids, to be eliminated to restore normal mitochondrial structure and functions. Under severe oxidative stress condition, mitochondrial dynamics (fission/fusion) and mitophagy are predominantly activated to rescue mitochondrial structure and functions. Additionally, MDVs generation can be also triggered as the major MQC machinery to cope with unhealthy mitochondria when mitophagy is unsuccessful for eliminating the damaged mitochondria or mitochondrial fission/fusion fail to recover the mitochondrial structure and functions. This review summarizes the current knowledge on MDVs and discuss their roles in physiologic and pathophysiologic conditions. In addition, the potential clinical relevance of MDVs in therapeutics and diagnostics of kidney stone disease (KSD) are emphasized. [ABSTRACT FROM AUTHOR]

Ischemic stroke, a global health concern, demands comprehensive exploration due to its substantial impact. This review delves into critical aspects, notably excitotoxicity and calcium dysregulation, which play pivotal roles in irreversible neuronal damage. Excitotoxicity, initiated by glutamate pathways, underscores the urgency of understanding these intricate mechanisms. The focus shifts to calcium dysregulation, a key contributor to ischemic cell death. Various ion channels, pumps, and receptors are intricately involved in this process, emphasizing the need for a nuanced understanding. Amidst these complexities, extracellular vesicles (EVs) emerge as crucial mediators in intercellular communication. Once considered cellular debris, EVs now present promising potential in stroke therapy. However, challenges in EV isolation and analysis are acknowledged, emphasizing the importance of reproducible biomarkers. As EVs exhibit multifaceted impacts on neuroinflammation, neurogenesis, and angiogenesis, their role in stroke pathophysiology becomes increasingly complex. With ongoing studies that provide a comprehensive perspective, EVs are positioned as promising candidates for both diagnostic biomarkers and therapeutic interventions in ischemic stroke. [ABSTRACT FROM AUTHOR]

This paper investigates the effect of involving electric vehicles (EVs) in the load profile on the generation system. The impact was studied from a reliability perspective on Saudi Arabia's total generation system capacity as one source supplying the expected load for the year 2030. The EV load profile was then added. The outcomes were examined considering the gradual penetration percentage to the total load. The reliability indices measured are the loss of load probability (LOLP) and the expected energy not supplied (EENS). The results show that the estimated generation system of Saudi Vision 2030 will not withstand the estimated number of EVs without negatively impacting reliability. Similarly, the reliability assessment was conducted for the central region considering EVs in Riyadh City to verify Saudi Vision 2030. The results show that EV integration will greatly affect the electrical network's reliability. Furthermore, a sensitivity analysis was conducted for Saudi Arabia and the central region to assess the generation system better. The study shows that investing in the generation infrastructure is essential to handle EV growth for the upcoming years. The work introduced in this paper will also help decision-makers make appropriate planning decisions in the future. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) enriched with bioactive molecules have gained considerable attention in nanotechnology because they are critical to intercellular communication while maintaining low immunological impact. Among biological matrices, urine has emerged as a noninvasive source of extracellular-contained liquid biopsy, currently of interest as a readout for physiological adaptations. Therefore, we aimed to evaluate chronic adaptations of endurance sport practice in terms of urinary EV parameters and evaluated by food consumption assessment. Two balanced groups of 13 inactive controls vs. triathlon athletes were enrolled; their urinary EVs were obtained by differential ultracentrifugation and analyzed by dynamic light scattering and transmission electron and atomic force microscopy. The cargo was analyzed by means of purine and miRNA content through HPLC-UV and qRT-PCR. Specific urinary EV signatures differentiated inactive versus endurance-trained in terms of peculiar shape. Particularly, a spheroid shape, smaller size, and lower roughness characterize EVs from triathletes. Metabolic and regulatory miRNAs often associated with skeletal muscle (i.e., miR378a-5p, miR27a-3p, miR133a, and miR206) also accounted for a differential signature. These miRNAs and guanosine in urinary EVs can be used as a readout for metabolic status along with the shape and roughness of EVs, novel informative parameters that are rarely considered. The network models allow scholars to entangle nutritional and exercise factors related to EVs' miRNA and purine content to depict metabolic signatures. All in all, multiplex biophysical and molecular analyses of urinary EVs may serve as promising prospects for research in exercise physiology. [ABSTRACT FROM AUTHOR]

Recent evidence has shown significant roles of mitochondria-derived vesicles (MDVs) in mitochondrial quality control (MQC) system. Under mild stress condition, MDVs are formed to carry the malfunctioned mitochondrial components, such as mitochondrial DNA (mtDNA), peptides, proteins and lipids, to be eliminated to restore normal mitochondrial structure and functions. Under severe oxidative stress condition, mitochondrial dynamics (fission/fusion) and mitophagy are predominantly activated to rescue mitochondrial structure and functions. Additionally, MDVs generation can be also triggered as the major MQC machinery to cope with unhealthy mitochondria when mitophagy is unsuccessful for eliminating the damaged mitochondria or mitochondrial fission/fusion fail to recover the mitochondrial structure and functions. This review summarizes the current knowledge on MDVs and discuss their roles in physiologic and pathophysiologic conditions. In addition, the potential clinical relevance of MDVs in therapeutics and diagnostics of kidney stone disease (KSD) are emphasized. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) possess cardioprotection in acute myocardial infarction. Nevertheless, the therapeutic intervention potential and the molecular mechanism of EVs from NMN (Nicotinamide mononucleotide) preconditioned hUCMSCs (N-EVs) in acute myocardial infarction remains unknown. In the present study, EVs from hUCMSCs (M-EVs) and N-EVs were identified by electron microscopy, immunoblotting and nanoparticle tracking analysis. Compared with M-EVs, N-EVs significantly increased the proliferation, migration, and angiogenesis of HUVECs. Meanwhile, N-EVs markedly reduced apoptosis and cardiac fibrosis and promoted angiogenesis in the peri-infarct region in the MI rats. A high-throughput miRNA sequencing and qPCR methods analysis revealed that miR-210-3p was abundant in N-EVs and the expression of miR-210-3p was obviously upregulated in HUVECs after N-EVs treated. Overexpression of miR-210-3p in HUVECs significantly enhanced the tube formation, migration and proliferative capacities of HUVECs. However, downregulation of miR-210-3p in HUVECs markedly decreased the tube formation, migration and proliferative capacities of HUVECs. Furthermore, bioinformatics analysis and luciferase assays revealed that EphrinA3 (EFNA3) was a direct target of miR-210-3p. Knockdown of miR-210-3p in N-EVs significantly impaired its ability to protect the heart after myocardial infarction. Altogether, these results indicated that N-EVs promoted the infarct healing through improvement of angiogenesis by miR-210-3p via targeting the EFNA3. Created with Biorender.com. [ABSTRACT FROM AUTHOR]

Aging is a complex, multifaceted degenerative process characterized by a progressive accumulation of macroscopic and microscopic modifications that cause a gradual decline of physiological functions. During the last few years, strategies to ease and counteract senescence or even rejuvenate cells and tissues were proposed. Here we investigate whether young cell secretome-derived extracellular vesicles (EVs) ameliorate the cellular and physiological hallmarks of aging in senescent cells. In addition, based on the assumption that extracellular matrix (ECM) provides biomechanical stimuli, directly influencing cell behavior, we examine whether ECM-based bio-scaffolds, obtained from decellularized ovaries of young swine, stably maintain the rejuvenated phenotype acquired by cells after exposure to young cell secretome. The results obtained demonstrate that young cells release EVs endowed with the ability to counteract aging. In addition, comparison between young and aged cell secretomes shows a significantly higher miR-200 content in EVs produced using fibroblasts isolated from young donors. The effect exerted by young cell secretome-derived EVs is transient, but can be stabilized using a young ECM microenvironment. This finding indicates a synergistic interaction occurring among molecular effectors and ECM-derived stimuli that cooperate to control a unique program, driving the cell clock. The model described in this paper may represent a useful tool to finely dissect the complex regulations and multiple biochemical and biomechanical cues driving cellular biological age. [ABSTRACT FROM AUTHOR]

Patients with advanced stage breast cancer need novel therapies. New potential treatments have been developed, such as adoptive cellular therapies and alternative cell-free immunotherapies. The goal of this study was to assess the cytotoxicity of three of the patient-derived immune components, CTLs, NK cells and NK-derived EVs, and evaluate the potential for the development of novel therapy against breast cancer. CTLs were activated against MUC-1 antigen. The in vitro cytotoxic activity of three components was assessed with flow cytometry and in vivo study revealed the efficacy of adoptive cell therapy. Overall, CTLs exhibited the highest cytotoxicity against spheroids of MCF7 breast adenocarcinoma, reaching in all cases higher than double the percentage of NK cells' cytotoxicity. NK-derived EVs exhibited the lowest effect against MCF7 spheroids comparing to the two cell populations. MUC-1 specific CTLs were evaluated with adoptive cell therapy mice study and appeared to be well tolerable and moderately efficacious. More studies need to be performed with CTLs to evaluate safety and efficacy in order to assess their clinical potential, while NK cells and NK-derived EVs are promising candidates that require more experiments to enhance their cytotoxicity. [ABSTRACT FROM AUTHOR]

Cell-secreted extracellular vesicles (EVs), carrying components such as RNA, DNA, proteins, and metabolites, serve as candidates for developing non-invasive solutions for monitoring health and disease, owing to their capacity to cross various biological barriers and to become integrated into human sweat. However, the evidence for sweat-associated EVs providing clinically relevant information to use in disease diagnostics has not been reported. Developing cost-effective, easy, and reliable methodologies to investigate EVs' molecular load and composition in the sweat may help to validate their relevance in clinical diagnosis. We used clinical-grade dressing patches, with the aim being to accumulate, purify and characterize sweat EVs from healthy participants exposed to transient heat. The skin patch-based protocol described in this paper enables the enrichment of sweat EVs that express EV markers, such as CD63. A targeted metabolomics study of the sweat EVs identified 24 components. These are associated with amino acids, glutamate, glutathione, fatty acids, TCA, and glycolysis pathways. Furthermore, as a proof-of-concept, when comparing the metabolites' levels in sweat EVs isolated from healthy individuals with those of participants with Type 2 diabetes following heat exposure, our findings revealed that the metabolic patterns of sweat EVs may be linked with metabolic changes. Moreover, the concentration of these metabolites may reflect correlations with blood glucose and BMI. Together our data revealed that sweat EVs can be purified using routinely used clinical patches, setting the foundations for larger-scale clinical cohort work. Furthermore, the metabolites identified in sweat EVs also offer a realistic means to identify relevant disease biomarkers. This study thus provides a proof-of-concept towards a novel methodology that will focus on the use of the sweat EVs and their metabolites as a non-invasive approach, in order to monitor wellbeing and changes in diseases. [ABSTRACT FROM AUTHOR]

Flavonoids enhance the self-renewal and differentiation potential of mesenchymal stem cells (MSCs) and have therapeutic activities, including regenerative, anti-oxidative, and anti-inflammatory effects. Recent studies have revealed that MSC-derived extracellular vesicles (MSC-EVs) have therapeutic effects on tissue regeneration and inflammation. To facilitate further research on the therapeutic potential of MSC-EVs derived from flavonoid-treated MSCs, we surveyed the production of EVs and their therapeutic applications in wound regeneration. MSCs treated with flavonoids enhanced EV production twofold compared with naïve MSCs. EVs produced by MSCs treated with flavonoids (Fla-EVs) displayed significant anti-inflammatory and wound-healing effects in vitro. The wound-healing capacity of EVs was mediated by the upregulation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Interestingly, the protein level of p-ERK under inhibition of MEK signals was maintained in Fla-EV-treated fibroblasts, suggesting that Fla-EVs have a higher therapeutic potential than naïve MSC-EVs (Cont-EVs) in wound healing. Moreover, the in vivo wound closure effect of the Fla-EVs showed significant improvement compared with that of the flavonoid-only treatment group and the Cont-EVs. This study provides a strategy for the efficient production of EVs with superior therapeutic potential using flavonoids. [ABSTRACT FROM AUTHOR]

Cell‐cell communication is an essential aspect of multicellular life, key for coordinating cell proliferation, growth, and death in response to environmental changes. Whilst caspases are well‐known for facilitating apoptotic and pyroptotic cell death, several recent investigations are uncovering new roles for these enzymes in biological scenarios requiring long‐range intercellular signalling mediated by extracellular vesicles (EVs). EVs are small membrane‐bound nanoparticles released from cells that may carry and deliver cargo between distant cells, thus helping to coordinate their behaviour. Intriguingly, there is emerging evidence indicating a key contribution of caspases in the biogenesis of EVs, the selection of their cargo content, and EV uptake/function in recipient cells. Here, we discuss the latest findings supporting the interplay between caspases and EVs, and the biological relevance of this molecular convergence for cellular signalling, principally in non‐apoptotic scenarios. [ABSTRACT FROM AUTHOR]

Mesenchymal stem/stromal cells (MSCs) are multipotent somatic cells that have been widely explored in the field of regenerative medicine. MSCs possess the ability to secrete soluble factors as well as lipid bound extracellular vesicles (EVs). MSCs have gained increased interest and attention as a result of their therapeutic properties, which are thought to be attributed to their secretome. However, while the use of MSCs as whole cells pose heterogeneity concerns and survival issues post-transplantation, such limitations are absent in cell-free EV-based treatments. EVs derived from MSCs are promising therapeutic agents for a range of clinical conditions and disorders owing to their immunomodulatory, pro-regenerative, anti-inflammatory, and antifibrotic activity. Recent successes with preclinical studies using EVs for repair and regeneration of damaged tissues such as cardiac tissue, lung, liver, pancreas, bone, skin, cornea, and blood diseases are discussed in this review. We also discuss delivery strategies of EVs using biomaterials as delivery vehicles through systemic or local administration. Despite its effectiveness in preclinical investigations, the application of MSC-EV in clinical settings will necessitate careful consideration surrounding issues such as: i) scalability and isolation, ii) biodistribution, iii) targeting specific tissues, iv) quantification and characterization, and v) safety and efficacy of dosage. The future of EVs in regenerative medicine is promising yet still needs further investigation on enhancing the efficacy, scalability, and potency for clinical applications. • MSC-derived EVs are promising therapeutic agents for several clinical conditions. • Complexity of MSC-EV cargo and effects of culture environments are discussed. • Challenges in MSC-EV manufacturing and possible solutions are addressed. • Biomanufacturing of MSC-EVs requires careful considerations of GMP-compliant processes. [ABSTRACT FROM AUTHOR]

Ageing is associated with notorious alterations in neurons, i.e., in gene expression, mitochondrial function, membrane degradation or intercellular communication. However, neurons live for the entire lifespan of the individual. One of the reasons why neurons remain functional in elderly people is survival mechanisms prevail over death mechanisms. While many signals are either pro-survival or pro-death, others can play both roles. Extracellular vesicles (EVs) can signal both pro-toxicity and survival. We used young and old animals, primary neuronal and oligodendrocyte cultures and neuroblastoma and oligodendrocytic lines. We analysed our samples using a combination of proteomics and artificial neural networks, biochemistry and immunofluorescence approaches. We found an age-dependent increase in ceramide synthase 2 (CerS2) in cortical EVs, expressed by oligodendrocytes. In addition, we show that CerS2 is present in neurons via the uptake of oligodendrocyte-derived EVs. Finally, we show that age-associated inflammation and metabolic stress favour CerS2 expression and that oligodendrocyte-derived EVs loaded with CerS2 lead to the expression of the antiapoptotic factor Bcl2 in inflammatory conditions. Our study shows that intercellular communication is altered in the ageing brain, which favours neuronal survival through the transfer of oligodendrocyte-derived EVs containing CerS2. [ABSTRACT FROM AUTHOR]

α-Synuclein is a protein linked to various synuclein-associated diseases ('synucleinopathies'), including Parkinson's disease, dementia with Lewy Bodies and multiple system atrophy, and is highly expressed in the central nervous system and in erythrocytes. Moreover, α-synuclein-containing erythrocyte-derived extracellular vesicles may be involved in the pathogenesis of synucleinopathies and their progression across the blood–brain barrier. Several post-translational modifications of α-synuclein have been reported in brain inclusions, including S129 phosphorylation, but fewer have been found in erythrocytes. In this study, we analysed the post-translational modifications of erythrocyte α-synuclein using liquid chromatography–mass spectrometry. We found that all lysine residues in the α-synuclein protein could be modified by acetylation, glycation, ubiquitination or SUMOylation but that phosphorylation, nitration and acylation were uncommon minor post-translational modifications in erythrocytes. Since the post-translational modification of lysine residues has been implicated in both membrane association and protein clearance, our findings provide new insight into how synucleinopathies may progress and suggest possible therapeutic strategies designed to target α-synuclein. [ABSTRACT FROM AUTHOR]

Cellular senescence, an evolutionarily conserved mechanism that prevents the proliferation of damaged cells, is a very relevant cellular response involved in both physiological and pathological conditions. Even though senescent cells are stably growth arrested, they exhibit a complex and poorly understood secretory phenotype, known as senescence‐associated secretory phenotype, composed of soluble proteins and extracellular vesicles (EVs). Extracellular vesicles were initially described as a waste management mechanism to remove damaged components of cellular metabolism, but increasing evidence shows that EVs could also play important roles in intercellular communication. Recently, some studies showed that EVs could have fundamental functions during cellular senescence. Our purpose in this review is to clarify the increasing literature on the role of EVs in cellular senescence as key mediators in cell‐to‐cell communication. [ABSTRACT FROM AUTHOR]

According to the Indian health line report, 12% of the population suffer from abnormal thyroid functioning. The major challenge in this disease is that the existence of hypothyroid may not propagate any noticeable symptoms in its early stages. However, delayed treatment of this disease may lead to several other health problems, such as fertility issues and obesity. Therefore, early treatment is essential for patient survival. The proposed technology could be used for the prediction of hypothyroid disease and its severity during its early stages. Though several classification and regression algorithms are available for the prediction of hypothyroid using clinical information, there exists a gap in knowledge as to whether predicted outcomes may reach a higher accuracy or not. Therefore, the objective of this research is to predict the existence of hypothyroidism with higher accuracy by optimizing the estimator list of the pycaret classifier model. With this overview, a blunge calibration intelligent feature classification model that supports the assessment of the presence of hypothyroidism with high accuracy is proposed. A hypothyroidism dataset containing 3163 patient details with 23 independent and one dependent feature from the University of California Irvine (UCI) machine-learning repository was used for this work. We undertook dataset preprocessing and determined its incomplete values. Exploratory data analysis was performed to analyze all the clinical parameters and the extent to which each feature supports the prediction of hypothyroidism. ANOVA was used to verify the F-statistic values of all attributes that might highly influence the target. Then, hypothyroidism was predicted using various classifier algorithms, and the performance metrics were analyzed. The original dataset was subjected to dimensionality reduction by using regressor and classifier feature-selection algorithms to determine the best subset components for predicting hypothyroidism. The feature-selected subset of the clinical parameters was subjected to various classifier algorithms, and its performance was analyzed. The system was implemented with python in the Spyder editor of Anaconda Navigator IDE. Investigational results show that the Gaussian naive Bayes, AdaBoost classifier, and Ridge classifier maintained the accuracy of 89.5% for the regressor feature-selection methods. The blunge calibration regression model (BCRM) was designed with naive Bayes, AdaBoost, and Ridge as the estimators with accuracy optimization and with soft blending based on the sum of predicted probabilities of classifiers. The proposed BCRM showed 99.5% accuracy in predicting hypothyroidism. The implementation results show that the Kernel SVM, KNeighbor, and Ridge classifier maintained an accuracy of 87.5% for the classifier feature-selection methods. The blunge calibration classifier model (BCCM) was developed with Kernel SVM, KNeighbor, and Ridge as the estimators, with accuracy optimization and with soft blending based on the sum of predicted probabilities of classifiers. The proposed BCCM showed 99.7% accuracy in predicting hypothyroidism. The main contribution of this research is the design of BCCM and BCRM models that were built with accuracy optimization with soft blending based on the sum of predicted probabilities of classifiers. The BCRM and BCCM models uniqueness's are achieved by updating the estimators list with the effective classifiers and regressors that suit the application at runtime. [ABSTRACT FROM AUTHOR]

With the global energy crisis, increasing demand, and a national-level emphasis on electric vehicles (EVs), numerous innovations are being witnessed throughout the EV industry. EVs are equipped with sensors that maintain a sustainable environment for the betterment of society and enhance human sustainability. However, at the same time, as is the case for any new digital technology, they are susceptible to threats to security and privacy. Recent incidents demonstrate that these sensors have been misused for car and energy theft, financial fraud, data compromise, and have caused severe health and safety problems, amongst other things. To the best of our knowledge, this paper provides a first systematic analysis of EV sustainability, digital technologies that enhance sustainability, their potential cybersecurity threats, and corresponding defense. Firstly, three robust taxonomies have been presented to identify the dangers that can affect long-term sustainability domains, including (1) life and well-being, (2) safe environment, and (3) innovation and development. Second, this research measures the impact of cybersecurity threats on EVs and correspondingly to their sustainability goals. Third, it details the extent to which specific security controls can mitigate these threats, thereby allowing for a smooth transition toward secure and sustainable future smart cities. [ABSTRACT FROM AUTHOR]

Cytolethal distending toxin (CDT) is produced by a range of Gram-negative pathogenic bacteria such as Campylobacter jejuni. CDT represents an important virulence factor that is a heterotrimeric complex composed of CdtA, CdtB, and CdtC. CdtA and CdtC constitute regulatory subunits whilst CdtB acts as the catalytic subunit exhibiting phosphatase and DNase activities, resulting in cell cycle arrest and cell death. Extracellular vesicle (EV) secretion is an evolutionarily conserved process that is present throughout all kingdoms. Mammalian EVs play important roles in regular cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses. Here, we demonstrate that CDT targets the endo-lysosomal compartment, partially evading lysosomal degradation and exploiting unconventional secretion (EV release), which is largely involved in bacterial infections. CDT-like effects are transferred by Caco-2 cells to uninfected heterologous U937 and homologous Caco-2 cells. The journey of EVs derived from CDT-treated Caco-2 cells is associated with both intestinal and myeloid tumour cells. EV release represents the primary route of CDT dissemination, revealing an active toxin as part of the cargo. We demonstrated that bacterial toxins could represent suitable tools in cancer therapy, highlighting both the benefits and limitations. The global cell response involves a moderate induction of apoptosis and autophagic features may play a protective role against toxin-induced cell death. EVs from CDT-treated Caco-2 cells represent reliable CDT carriers, potentially suitable in colorectal cancer treatments. Our data present a potential bacterial-related biotherapeutic supporting a multidrug anticancer protocol. [ABSTRACT FROM AUTHOR]

The objective of the study was to identify extracellular vesicle (EV) microRNAs (miRNAs) that play important roles in knee osteoarthritis (OA). Models of knee OA were surgically induced in nine male Sprague-Dawley rats. Tissue samples were collected at 0 weeks (Control), 6 weeks (6 weeks), and 12 weeks (12 weeks). The EVs were isolated and analyzed for size. Various biomarkers, including recombinant tetraspanin 30 cluster of differentiation (CD)63 and CD9 were detected. An Agilent array was used to screen for differentially expressed (DE) miRNAs. The levels of DE miRNAs and their target mRNAs were evaluated by quantitative reverse transcription–polymerase chain reaction and western blotting. The viability, proliferation, and apoptosis of lipopolysaccharide (LPS)-induced human synovial cells (HSCs) were examined by using Cell Counting Kit-8, EdU (5-ethynyl-2′-deoxyuridine), and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assays, respectively. The OA model rats had significantly increased levels of inflammatory activity, damaged cells, and rough articular cartilage when compared with rats in the control group. The EVs from the model rats appeared as round vesicle-like structures with a mean diameter of ∼145 nm. Five miRNAs that showed gradual increases in the model rats were selected for further analysis; those miRNAs included miR-127-3p, miR-132-3p, miR-141-3p, miR-345-5p, and miR-382-5p. miR-382-5p was found to reduce the viability and proliferation and promote the apoptosis of LPS-induced HSCs. Moreover, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was negatively regulated by miR-382-5p. Our findings revealed that EVs produced by the OA rats contained miR-382-5p, which might reduce cell viability and proliferation, and promote cell apoptosis by targeting PTEN. [ABSTRACT FROM AUTHOR]