Abstract
Small extracellular vesicles (EVs) have emerged as a focal point of EV research due to their significant role in a wide range of physiological and pathological processes within living ...systems. However, uncertainties about the nature of these vesicles have added considerable complexity to the already difficult task of developing EV‐based diagnostics and therapeutics. Whereas small EVs have been shown to be negatively charged, their surface charge has not yet been properly quantified. This gap in knowledge has made it challenging to fully understand the nature of these particles and the way they interact with one another, and with other biological structures like cells. Most published studies have evaluated EV charge by focusing on zeta potential calculated using classical theoretical approaches. However, these approaches tend to underestimate zeta potential at the nanoscale. Moreover, zeta potential alone cannot provide a complete picture of the electrical properties of small EVs since it ignores the effect of ions that bind tightly to the surface of these particles. The absence of validated methods to accurately estimate the actual surface charge (electrical valence) and determine the zeta potential of EVs is a significant knowledge gap, as it limits the development of effective label‐free methods for EV isolation and detection. In this study, for the first time, we show how the electrical charge of small EVs can be more accurately determined by accounting for the impact of tightly bound ions. This was accomplished by measuring the electrophoretic mobility of EVs, and then analytically correlating the measured values to their charge in the form of zeta potential and electrical valence. In contrast to the currently used theoretical expressions, the employed analytical method in this study enabled a more accurate estimation of EV surface charge, which will facilitate the development of EV‐based diagnostic and therapeutic applications.
There is a growing interest to understand if and how the gut microbiome is causally linked to the pathogenesis and/or progression of diseases. While in vitro cell line models are commonly used for ...studying specific aspects of the host–microbe interaction, gnotobiotic murine models are considered the preferred platform for studying causality in microbiome research. Nevertheless, findings from animal studies provide limited opportunity for delineating various areas of interest to the human gut microbiome research. Gut-on-chips are biomimetics recapitulating intestinal physiology which enable investigation of bidirectional effects of the host and microbiome. We posit that they could advance causal and ecological gut microbiome research in three major areas: (i) diet–microbiome and drug–microbiome interaction; (ii) microbiome-targeted therapeutics pharmacoecology; and (iii) mechanistic studies of gut microbiome and microbiome-targeted intervention in extraintestinal pathologies.
Gnotobiotic murine models are currently the cornerstone of causal gut microbiome research. Nevertheless, they provide limited opportunity for delineating various areas of interest to the human gut microbiome research.Current in vitro microbial ecology and host–microbe coculture methods also have limited capacity for studying the ecological bidirectional interaction of host and gut microbiome.Gut-microbiome-on-chips provide physiological and ecological advantages over other in vitro methods, allowing for monitoring microbial growth and ecological dynamic as well as host–microbiome interactions while adjusting and measuring the ecologically relevant parameters (e.g., pH and O2 level) in real time.Gut-microbiome-on-chips could be connected with other chips to model gut–liver, gut–lung, or gut–brain axes.Gut-microbiome-on-chip could expand microbiome research in three major areas: (i) diet–microbiome and drug–microbiome interactions; (ii) pharmacoecology of microbiome-targeted therapeutics; and (iii) mechanistic studies of gut microbiome and microbiome-targeted intervention in extraintestinal pathologies within the context of a personalized and precision medicine framework.
The demand for rapid and accurate diagnosis of plant diseases has risen in the last decade. On-site diagnosis of single or multiple pathogens using portable devices is the first step in this ...endeavour. Despite extensive attempts to develop portable devices for pathogen detection, current technologies are still restricted to detecting known pathogens with limited detection accuracy. Developing new detection techniques for rapid and accurate detection of multiple plant pathogens and their associated variants is essential. Recent single DNA sequencing technologies are a promising new avenue for developing future portable devices for plant pathogen detection. In this review, we detail the current progress in portable devices and technologies used for detecting plant pathogens, the current position of emerging sequencing technologies for analysis of plant genomics, and the future of portable devices for rapid pathogen diagnosis.
A lab-on-a-chip device with a knot shaped microfluidic network is presented to enable trapping of single pollen grains at the entrances of a series of microchannels. This set-up serves to create ...identical growth conditions for serially arranged tip growing plant cells such as pollen tubes. The design consists of an inlet to introduce the pollen suspension into the chip, three outlets to evacuate excess medium or cells, a distribution chamber to guide the pollen grains toward the growth microchannels and a serial arrangement of microchannels with different geometries connected to the distribution chamber. These microchannels are to harbor the individual pollen tubes. Two different criteria were established to assess the efficiency and optimize the device: trapping probability and uniformity of fluid flow conditions within the microchannels. The performance of different geometries of the microfluidic network was numerically analyzed and experimentally tested.
Magnetic drug targeting (MDT) and magnetic-based drug/cargo delivery are emerging treatment methods which attracting the attention of many researchers for curing different cancers and artery diseases ...such as atherosclerosis. Herein, computational studies are accomplished by utilizing magnetic approaches for cancer and artery atherosclerosis drug delivery, including nanomagnetic drug delivery and magnetic-based drug/cargo delivery. For the first time, the four-layer structural model of the artery tissue and its porosity parameters are modeled in this study which enables the interaction of particles with the tissue walls in blood flow. The effects of parameters, including magnetic field strength (MFS), magnet size, particle size, the initial position of particles, and the relative magnetic permeability of particles, on the efficacy of MDT through the artery walls are characterized. The magnetic particle penetration into artery layers and fibrous cap (the covering layer over the inflamed part of the artery) is further simulated. The MDT in healthy and diseased arteries demonstrates that some of the particles stuck in these tissues due to the collision of particles or blood flow deviation in the vicinity of the inflamed part of the artery. Therefore the geometry of artery and porosity of its layers should be considered to show the real interaction of particles with the artery walls. Also, the results show that increasing the particles/drug/cargo size and MFS leads to more particles/drug/cargo retention within the tissue. The present work provides insights into the decisive factors in arterial MDT with an obvious impact on locoregional cancer treatment, tissue engineering, and regenerative medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Over 27 million individuals are affected every year worldwide with central nervous system (CNS) injuries. These injuries include but are not limited to traumatic brain injury (TBI) and spinal cord ...injury (SCI). CNS injuries remain a significant public health concern which demands reliable tools for rapid, on-sight, on-field, and point-of-care diagnostic (POC) solutions. To address these challenges, we developed a low-cost, open-source, hand-held, portable, and POC detection technology, termed as MicroDrop (μDrop), which can simultaneously detect up to eight target biomolecules and display results in both analog and digital formats. The data acquired is stored wirelessly in a cloud server for further investigation and statistical analysis. Multiplexing capability of μDrop and immuno-biosensors detects and quantifies Cleaved-Tau Protein (C-Tau) and Neuron-Filament (NFL) proteins in the blood of TBI patients. Immuno-biosensors rapidly sense the two target proteins in less than 30 min, with μDrop and a conventional potentiostat. C-Tau and NFL were selectively detected with μDrop within the dynamic range of 10 pg/mL - 100 ng/mL and the sensitivity range of 47 μA/pg mm2 - 65 μA/pg mm2. Comparing the biosensing performance with enzyme-linked immunosorbent assays (ELISA) shows that the immuno-biosensors combined with μDrop could successfully differentiate between clinical controls and injured patients.
Display omitted
•The development of opensource multi-analyte portable electrochemical sensing device (μDrop).•μDrop performs differential pulse voltammetry mode of electrochemical sensing.•The comparable performance of μDrop to a commercial potentiostat.•Accurate detection of cleaved tau (C-Tau) and neuron filament light (NFL) in the blood of TBI patients.
Protein thermostability engineering is a powerful tool to improve resistance of proteins against high temperatures and thereafter broaden their applications. For efficient protein thermostability ...engineering, different thermostability-classified data sources including sequences and 3D structures are needed for different protein families. However, no data source is available providing such data easily. It is the first release of ProtDataTherm database for analysis and engineering of protein thermostability which contains more than 14 million protein sequences categorized based on their thermal stability and protein family. This database contains data needed for better understanding protein thermostability and stability engineering. Providing categorized protein sequences and structures as psychrophilic, mesophilic and thermophilic makes this database useful for the development of new tools in protein stability prediction. This database is available at http://profiles.bs.ipm.ir/softwares/protdatatherm. As a proof of concept, the thermostability that improves mutations were suggested for one sample protein belonging to one of protein families with more than 20 mesophilic and thermophilic sequences and with known experimentally measured ΔT of mutations available within ProTherm database.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cellulose nanocrystals (CNCs) are rapidly increasingly used nanomaterials with a large surface area, outstanding mechanical characteristics, and the capacity to exhibit variable surface chemistry, ...allowing them to be incorporated into a variety of matrices. An examination of information from various firms on scales of tonnes per day suggests an increasing tendency for the use of CNC-based products. Here, we review recent advances in microstructural characterization of CNC-based suspensions and hydrogels utilizing imaging and rheological approaches. We demonstrate how microscopy and rheology can be utilized to adjust and improve the final macro characteristics of CNC-based systems. Novel applications, e.g., 3D printing, for CNC suspensions and gels are also introduced. Indeed, because CNC-based products show significant potential for biomedical, energy, cosmetics, filtration, and food applications, using existing characterization methods and models to fine-tune the CNC colloid properties cannot be ruled out. All references were selected from recent publications (earlier than 2010).
Purpose
A numerical model of an unsteady laminar free convection flow and heat transfer is studied in a cavity that comprises a vertical flexible thin partition.
Design/methodology/approach
The left ...and right vertical boundaries are isothermal, while the horizontal boundaries are insulated. Moreover, the thin partition, placed in the geometric centerline of the enclosure, is considered to be hyper elastic and diathermal. Galerkin finite-element methods, the system of partial differential equations along with the appropriate boundary conditions are transformed to a weak form through the fluid-structure interaction and solved numerically.
Findings
The heat transfer characteristics of the enclosure with rigid and flexible partitions are compared. The effect of Rayleigh number and Young’s modulus on the maximum nondimensional stress and final deformed shape of the membrane is addressed.
Originality/value
Incorporation of vertical thin flexible membrane in middle of a cavity has numerous industrial applications, and it could noticeably affect the heat and mass transfer in the enclosure.
Ischemic diseases such as myocardial infarction, ischemic stroke, and critical limb ischemia are immense public health challenges. Current pharmacotherapy and surgical approaches are insufficient to ...completely heal ischemic diseases and are associated with a considerable risk of adverse effects. Alternatively, human mesenchymal stem cells (hMSCs) have been shown to exhibit immunomodulation, angiogenesis, and paracrine secretion of bioactive factors that can attenuate inflammation and promote tissue regeneration, making them a promising cell source for ischemic disease therapy. This review summarizes the pathogenesis of ischemic diseases, discusses the potential therapeutic effects and mechanisms of hMSCs for these diseases, and provides an overview of challenges of using hMSCs clinically for treating ischemic diseases.
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