Search Results (82)

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

The detection of particulate matter, particularly pathogenic bacteria, is essential in environmental monitoring, food safety, and clinical diagnostics. Among the various sensing techniques used, cantilever-based sensors offer a promising platform for label-free, real-time detection due to their high sensitivity. Here, we present a coupled cantilever sensor incorporating interdigitated comb-shaped structures to enhance dielectrophoretic (DEP) capture of Escherichia coli in liquid samples. During operation, one cantilever is externally actuated and the other oscillates passively through fluid-mediated coupling. The sensor was experimentally evaluated across a broad concentration range from 10 to 10⁵ cells/mL and the resonant frequency shifts were recorded for both beams. The results showed a strong linear frequency shift across all tested concentrations, without saturation. This demonstrates the sensor’s ability to detect both trace and high bacterial loads without needing recalibration. High frequency shifts of 4863 Hz were recorded for 10⁵ cells/mL and 225 Hz for the lowest concentration of 10 cells/mL, giving a limit of detection of 10 cells/mL. The sensor also showed a higher signal to noise ratio of 265.7 compared to previously reported designs. These findings showed that the enhanced sensor design enables sensitive, linear, and reliable bioparticle detection across a wide range, making it suitable for diverse applications. Full article

The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating the separation and focusing of various cell types, including blood cells, circulating tumor cells (CTCs), and microalgae. However, the viscoelastic nature of the particles imposes limitations in the handling of submicron-sized particles, due to a significant decrease in the viscoelastic force acting on the particle. In this study, we propose a microfluidic device featuring a cruciform cross-sectional microchannel with 45 µm and 45 µm of its vertical and horizontal size, respectively. The cruciform microchannel, which has a 270° reflex angle on four corners, can increase the viscoelastic force on the particles, allowing the device to focus submicron-sized particles down to 180 nm in a single-stream manner. It is important to note that the single-stream formation was maintained, while the channel width at the outlet region was drastically increased, allowing for the enrichment of submicron-sized particles. For biological feasibility, the proposed device also demonstrates the single-stream focusing on biological particles such as bacteria. The presented microfluidic device would have great potential for the focusing and enrichment of nanoparticles including bacteria in a highly robust manner, expecting its use in the various fields such as diverse biological analysis and biomedical research. Full article

γ-Secretase has primarily been studied in neurons, whereas increasing evidence highlights its importance in microglia. Previous research has shown that the pharmacological inhibition of γ-secretase impairs microglial phagocytic activity. In this study, we used a genetically encoded Förster resonance energy transfer (FRET)-based biosensor to record γ-secretase activity, aiming to determine if naturally occurring cell-by-cell variations in endogenous γ-secretase activity are associated with phagocytic activity. Using the Notch1 N100 Y-T biosensor, we found that the regulation of endogenous γ-secretase activity varies among individual BV-2 microglial cells. Our multiplexed time-lapse imaging revealed that the phagocytosis of E. coli bioparticles was impaired in cells with lower γ-secretase activity compared to those with higher activity. Complementary biochemical analysis, utilizing Zymosan bioparticles and fluorescence-activated cell sorting (FACS), further demonstrated that cells with reduced phagocytic activity exhibited decreased endogenous γ-secretase activity. Collectively, our confirmatory study supports previous findings that microglial phagocytic activity is closely linked to γ-secretase and emphasizes the essential role of γ-secretase in microglia. Full article

Rural villages function as relatively self-sustained production and living units with well-developed infrastructure. In this setting, investigating the transmission pathways of airborne biological particles, including pathogenic microorganisms, is pivotal for ensuring the health of residents. This study investigated the sources and dispersion of biogenic particulate matter in rural ambient air and factors influencing their behavior. Potential bioaerosol sources including livestock farming areas, composting sites, garbage dumps, and sewage treatment facilities were investigated using a calibrated portable bioaerosol detector to collect and analyze the dispersion of bioaerosol particles. The dispersal characteristics of Enterobacteriaceae were explored using an Andersen six-stage sampler. Livestock farming areas were the primary source of bioparticles. The distribution of the bioparticles varied significantly with environmental conditions. Key factors influencing their distribution included the dispersal capabilities due to wind speed and the processes of aggregation and coagulation of particles. The dispersal pathway of Enterobacteriaceae indicated that the inhabitants of residences near the dispersion source might be exposed to health risks from pathogenic bacteria present in bioparticles indoors. Understanding such characteristics and transmission patterns of bioparticles in rural environments provides a scientific basis for risk assessment and management strategies, with important implications for improving air-quality monitoring, public health policies, and environmental management in rural areas. Full article

Dielectrophoresis (DEP) has been widely employed in microfluidic platforms for particle or cell manipulation in biomedical science applications due to its accurate, fast, label-free, and low-cost diagnostic technique. However, the application of the DEP technique towards protein manipulation has yet to be extensively explored due to the challenges of the complexity of protein itself, such as its complex morphologies, extremely minuscule particle size, inherent electrical properties, and temperature sensitivity, which make it relatively more challenging. Furthermore, given that protein DEP investigation requires entering the micro- to nano-scale level of DEP configuration, various challenging factors such as electrohydrodynamic effects, electrolysis, joule heating, and electrothermal force that emerge will make it more difficult in realizing protein DEP investigation. This review study has discussed the fundamental theory of DEP and considerations toward protein DEP manipulation. In particular, it focused on the DEP theoretical principle towards protein, protein DEP application challenges, microfluidic platform considerations, medium considerations, and a critically reviewed list of protein bioparticles that have been investigated were all highlighted. Full article

Rationale: The role of the innate immune system in idiopathic pulmonary fibrosis (IPF) remains poorly understood. However, a functional myeloid compartment is required to remove dying cells and cellular debris, as well as to mediate innate immune responses against pathogens. Aberrant macrophage activity has been described in patients with post-acute sequelae of COVID fibrosis (PASC-F), and caveolin scaffolding domain (CSD) peptides have been found to attenuate inflammation and fibrosis in mouse lung injury models. Therefore, we examined, for the first time, the effects of CSD peptide LTI-2355 on the functional and synthetic properties of human myeloid cells isolated from lung explant tissue of donor lungs as well as IPF and PASC-F lung explant tissue. Methods and Results: CD45⁺ myeloid cells isolated from lung explant tissue from IPF and PASC-F patients exhibited an impaired capacity to clear autologous dead cells and cellular debris. The uptake of pathogen-coated bioparticles was impaired in myeloid cells from both fibrotic patient groups independent of the type of pathogen, highlighting an intrinsic functional cell impairment. LTI-2355 improved the phagocytic activity of both IPF and PASC-F myeloid cells, and this improvement was paired with decreased proinflammatory and pro-fibrotic synthetic activity. LTI-2355 was also shown to primarily target CD206-expressing IPF and PASC-F myeloid cells. Conclusions: Primary myeloid cells from IPF and PASC-F patients exhibit dysfunctional phagocytic and synthetic properties that are modulated by LTI-2355. LTI-2355 treatment of IPF myeloid cells resulted in significantly reduced sCD163, IFN-α2, IFN-γ, IL-2, IL-10, IL-12p40, and MMP-1 in the cell supernatant. This study highlights an additional mechanism of action of the CSD peptide in the treatment of IPF and progressive fibrotic lung disease. Full article

Active packaging using an edible coating could be an essential and sustainable alternative solution to preserve the properties of fruits and to prevent food loss and food waste. Fruits generate significant food wastes and losses. Reducing food waste is a global priority. For this research, nature-based solutions (NBSs) were applied, using micro-sized chitosan (CsMPs) and selenium microparticles (SeMPs), which are green-synthesized from black tea leaf extracts, and thyme essential oil. In this study, the effects of the new generation active food preservative coating agents formed from combinations of micro-sized chitosan (CsMPs) and selenium (SeMPs), and thyme essential oil (Oil) on the quality of “0900 Ziraat” sweet cherry fruits after harvest were investigated. After the fruits were coated with edible colloid solution, they were stored at 4 °C and 21 °C for 20 days, and quality parameter analyses were performed on days 0, 5, 10, 15, and 20. As a result of this study, it was determined that the application of CsMPs + SeMPs and the subsequent application of CsMPs + SeMPs + Oil from colloid solution coatings reduced weight loss, respiration, and decay rates. Also, it was determined that these applications were the most effective in preserving color values (L*, chroma, and hue), fruit firmness, total soluble solid (TSS) amount, acidity content and total phenolics, anthocyanin, and antioxidant capacity. These results show that CsMPs + SeMPs and CsMPs + SeMPs + Oil applications can be used as edible coatings to preserve the quality of sweet cherry fruits and extend their shelf life after harvest. This study’s results will contribute to obtaining micro-sized composite coating agents/agents produced with new technology to extend the shelf life. Full article

In this paper, enhanced rotational circulation in a circular microfluidic chamber driven by dual focused surface-acoustic-wave (SAW) beams is presented. To characterize the resonant frequency and focusing effect, we simulate the focused SAW field excited by an arc-shaped interdigital transducer patterned on a 128°Y-cut lithium-niobate (LiNbO₃) substrate using a finite element method. A full three-dimensional perturbation model of the combined system of the microfluidic chamber and the SAW device is conducted to obtain the acoustic pressure and acoustic streaming fields, which show rotational acoustic pressure and encircling streaming resulted in the chamber. Accordingly, the SAW acoustofluidic system is realized using microfabrication techniques and applied to perform acoustophoresis experiments on submicron particles suspending in the microfluidic chamber. The result verifies the rotational circulation motion of the streaming flow, which is attributed to enhanced angular momentum flux injection and Eckart streaming effect through the dual focused SAW beams. Our results should be of importance in driving particle circulation and enhancing mass transfer in chamber embedded microfluidic channels, which may have promising applications in accelerating bioparticle or cell reactions and fusion, enhancing biochemical and electrochemical sensing, and efficient microfluidic mixing. Full article

Acoustic trap, using ultrasound interference to ensnare bioparticles, has emerged as a versatile tool for life sciences due to its non-invasive nature. Bolstered by magnetic resonance imaging’s advances in sensing acoustic interference and tracking drug carriers (e.g., microbubble), acoustic trap holds promise for increasing MRI-guided microbubbles (MBs) accumulation in target microvessels, improving drug carrier concentration. However, accurate trap generation remains challenging due to complex ultrasound propagation in tissues. Moreover, the MBs’ short lifetime demands high computation efficiency for trap position adjustments based on real-time MRI-guided carrier monitoring. To this end, we propose a machine learning-based model to modulate the transducer array. Our model delivers accurate prediction of both time-of-flight (ToF) and pressure amplitude, achieving low average prediction errors for ToF (−0.45 µs to 0.67 µs, with only a few isolated outliers) and amplitude (−0.34% to 1.75%). Compared with the existing methods, our model enables rapid prediction (<10 ms), achieving a four-order of magnitude improvement in computational efficiency. Validation results based on different transducer sizes and penetration depths support the model’s adaptability and potential for future ultrasound treatments. Full article

Surface plasmon microscopy proves to be a potent tool for capturing interferometric scattering imaging data of individual particles at both micro and nanoscales, offering considerable potential for label-free analysis of bio-particles and bio-molecules such as exosomes, viruses, and bacteria. However, the manual analysis of acquired images remains a challenge, particularly when dealing with dense samples or strong background noise, common in practical measurements. Manual analysis is not only prone to errors but is also time-consuming, especially when handling a large volume of experimental images. Currently, automated methods for sensing and analysis of such data are lacking. In this paper, we develop an accelerated approach for surface plasmon microscopy imaging of individual particles based on combining the interference scattering model of single particle and deep learning processing. We create hybrid datasets by combining the theoretical simulation of particle images with the actual measurements. Subsequently, we construct a neural network utilizing the EfficientNet architecture. Our results demonstrate the effectiveness of this novel deep learning technique in classifying interferometric scattering images and identifying multiple particles under noisy conditions. This advancement paves the way for practical bio-applications through efficient automated particle analysis. Full article

Human serum albumin (HSA) corona formation on polymer microparticles of a spheroidal shape was studied using dynamic light scattering and Laser Doppler Velocimetry (LDV). Physicochemical characteristics of the albumin comprising the zeta potential and the isoelectric point were determined as a function of pH for various ionic strengths. Analogous characteristics of the polymer particles were analyzed. The adsorption of albumin on the particles was in situ monitored by LDV. The stability of the HSA-functionalized particle suspensions under various pHs and their electrokinetic properties were also determined. The deposition kinetics of the particles on mica, silica and gold sensors were investigated by optical microscopy, AFM and quartz microbalance (QCM) under diffusion and flow conditions. The obtained results were interpreted in terms of the random sequential adsorption model that allowed to estimate the range of applicability of QCM for determining the deposition kinetics of viruses and bacteria at abiotic surfaces. Full article

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids. Full article

The Anammox anaerobic fluidized bed microbial fuel cell (Anammox AFB-MFC) exhibits exceptional performance in both nitrogen removal and electricity generation, effectively eliminating ammonia nitrogen (NH₄⁺-N) and nitrite nitrogen (NO₂⁻-N) pollutants. This technology offers the advantages of high efficiency in nitrogen removal and low electricity consumption. By coupling an AFB with an MFC, the Anammox AFB-MFC was developed through the introduction of anaerobic ammonia-oxidizing bacteria (AnAOB) into MFC. Anammox AFB-MFC’s nitrogen removal ability was found to be superior at an influent COD concentration of 200 mg/L, as determined by a study conducted under unchanged conditions. Subsequently, an open and closed-circuit experiment was performed on the Anammox AFB-MFC system while maintaining a COD concentration of 200 mg/L in the influent. Remarkably, the reactor exhibited significantly enhanced nitrogen removal performance when electricity generation occurred. Throughout the entire experimental process, the reactor consistently maintained high nitrogen removal efficiency and electricity production performance. Under optimal experimental conditions, the reactor achieved a remarkable nitrogen removal rate of 91.8% and an impressive output voltage of 439.1 mV. Additionally, the generation of Anammox bioparticles in MFC significantly contributed to efficient pollutant removal. This study elucidates the impact of organic matter on both the nitrogen removal and electricity generation capabilities of Anammox AFB-MFC, as well as highlights the synergistic effect between MFC electricity generation and nitrogen removal in the reactor. Full article

High-efficient separation of (bio)microparticles has important applications in chemical analysis, environmental monitoring, drug screening, and disease diagnosis and treatment. As a label-free and high-precision separation scheme, dielectrophoresis (DEP) has become a research hotspot in microparticle separation, especially for biological cells. When processing cells with DEP, relatively high electric conductivities of suspending media are sometimes required to maintain the biological activities of the biosample, which results in high temperature rises within the system caused by Joule heating. The induced temperature gradient generates a localized alternating current electrothermal (ACET) flow disturbance, which seriously impacts the DEP manipulation of cells. Based on this, we propose a novel design of the (bio)microparticle separator by combining DEP with ACET flow to intensify the separation process. A coupling model that incorporates electric, fluid flow, and temperature fields as well as particle tracking is established to predict (bio)microparticle trajectories within the separator. Numerical simulations reveal that both ACET flow and DEP motion act in the same plane but in different directions to achieve high-precision separation between particles. This work provides new design ideas for solving the very tricky Joule heating interference in the DEP separation process, which paves the way for further improving the throughput of the DEP-based (bio)microparticle separation system. Full article