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Posttranslational modifications play a crucial role in governing cellular functions and protein behavior. Researchers have implicated dysregulated posttranslational modifications in protein misfolding, which results in cytotoxicity, particularly in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and Huntington disease. These aberrant posttranslational modifications cause proteins to gather in certain parts of the brain that are linked to the development of the diseases. This leads to neuronal dysfunction and the start of neurodegenerative disease symptoms. Cognitive decline and neurological impairments commonly manifest in neurodegenerative disease patients, underscoring the urgency of comprehending the posttranslational modifications' impact on protein function for targeted therapeutic interventions. This review elucidates the critical link between neurodegenerative diseases and specific posttranslational modifications, focusing on Tau, APP, α‐synuclein, Huntingtin protein, Parkin, DJ‐1, and Drp1. By delineating the prominent aberrant posttranslational modifications within Alzheimer disease, Parkinson disease, and Huntington disease, the review underscores the significance of understanding the interplay among these modifications. Emphasizing 10 key abnormal posttranslational modifications, this study aims to provide a comprehensive framework for investigating neurodegenerative diseases holistically. The insights presented herein shed light on potential therapeutic avenues aimed at modulating posttranslational modifications to mitigate protein aggregation and retard neurodegenerative disease progression. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the deadliest cancers worldwide due to the inability of existing methods for early diagnosis. Tumor-derived exosomes are nano-scale vesicles released from tumor cells to the extracellular environment, and their investigation can be very useful in both biomarkers for early cancer screening and treatment assessment. This research detected the exosomes via an ultrasensitive electrochemical biosensor containing gold nano-islands (Au-NIs) structures. This way, a high surface-area-to-volume ratio of nanostructures was embellished on the FTO electrodes to increase the chance of immobilizing the CD-151 antibody. In this way, a layer of gold was first deposited on the electrode by physical vapor deposition (PVD), followed by thermal annealing to construct primary gold seeds on the surface of the electrode. Then, gold seeds were grown by electrochemical deposition through gold salt. The cell-derived exosomes were successfully immobilized on the FTO electrode through the CD-151 antibody, and cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used in this research. In the CV method, the change in the current passing through the working electrode is measured so that the connection of exosomes causes the current to decrease. In the EIS method, surface resistance changes were investigated so that the binding of exosomes increased the surface resistance. Various concentrations of exosomes in both cell culture and blood serum samples were measured to test the sensitivity of the biosensor, which makes our biosensor capable of detecting 20 exosomes per milliliter. [ABSTRACT FROM AUTHOR]

Lung cancer is indeed a major cause of cancer‐related deaths worldwide. The development of tumors involves a complex interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, and microRNA expression, play a crucial role in this process. Changes in DNAm patterns can lead to the silencing of important genes involved in cellular functions, contributing to the development and progression of lung cancer. MicroRNAs and exosomes have also emerged as reliable biomarkers for lung cancer. They can provide valuable information about early diagnosis and treatment assessment. In particular, abnormal hypermethylation of gene promoters and its effects on tumorigenesis, as well as its roles in the Wnt signaling pathway, have been extensively studied. Epigenetic drugs have shown promise in the treatment of lung cancer. These drugs target the aberrant epigenetic modifications that are involved in the development and progression of the disease. Several factors have been identified as drug targets in non‐small cell lung cancer. Recently, combination therapy has been discussed as a successful strategy for overcoming drug resistance. Overall, understanding the role of epigenetic mechanisms and their targeting through drugs is an important area of research in lung cancer treatment. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the leading causes of cancer deaths in women worldwide. Magnetic fields have shown anti-tumor effects in vitro and in vivo as a non-invasive therapy method that can affect cellular metabolism remotely. Doxorubicin (DOX) is one of the most commonly used drugs for treating breast cancer patients. It can be assumed that combining chemotherapy and magnetotherapy is one of the most effective treatments for breast cancer. This study aimed to investigate the potential cytotoxic effect of DOX at low concentrations in combination with extremely low-frequency electromagnetic fields (ELF–EMF; 50 Hz; 20 mT). The breast cancer cell line MCF-7 was examined for oxidative stress, cell cycle, and apoptosis. MCF-7 cells were treated with various concentrations of DOX as an apoptosis-inducing agent and ELF–EMF. Cytotoxicity was examined using the MTT colorimetric assay at 12, 24, and 48 h. Consequently, concentration- and time-dependent cytotoxicity was observed in MCF-7 cells for DOX within 24 h. The MTT assay results used showed that a 2 μM concentration of DOX reduced cell viability to 50% compared with control, and as well, the combination of ELF–EMF and DOX reduced cell viability to 50% compared with control at > 0.25 μM doses for 24 h. In MCF-7 cells, combining 0.25 μM DOX with ELF–EMF resulted in increased ROS levels and DOX-induced apoptosis. Flow cytometry analysis, on the other hand, revealed enhanced arrest of MCF-7 cells in the G0-G1 phase of the cell cycle, as well as inducing apoptotic cell death in MCF-7 cells, implying that the synergistic effects of 0.25 μM DOX and ELF–EMF may represent a novel and effective agent against breast cancer. [ABSTRACT FROM AUTHOR]

Epigenetics has long been recognized as a significant field in biology and is defined as the investigation of any alteration in gene expression patterns that is not attributed to changes in the DNA sequences. Epigenetic marks, including histone modifications, non-coding RNAs, and DNA methylation, play crucial roles in gene regulation. Numerous studies in humans have been carried out on single-nucleotide resolution of DNA methylation, the CpG island, new histone modifications, and genome-wide nucleosome positioning. These studies indicate that epigenetic mutations and aberrant placement of these epigenetic marks play a critical role in causing the disease. Consequently, significant development has occurred in biomedical research in identifying epigenetic mechanisms, their interactions, and changes in health and disease conditions. The purpose of this review article is to provide comprehensive information about the different types of diseases caused by alterations in epigenetic factors such as DNA methylation and histone acetylation or methylation. Recent studies reported that epigenetics could influence the evolution of human cancer via aberrant methylation of gene promoter regions, which is associated with reduced gene function. Furthermore, DNA methyltransferases (DNMTs) in the DNA methylation process as well as histone acetyltransferases (HATs)/histone deacetylases (HDACs) and histone methyltransferases (HMTs)/demethylases (HDMs) in histone modifications play important roles both in the catalysis and inhibition of target gene transcription and in many other DNA processes such as repair, replication, and recombination. Dysfunction in these enzymes leads to epigenetic disorders and, as a result, various diseases such as cancers and brain diseases. Consequently, the knowledge of how to modify aberrant DNA methylation as well as aberrant histone acetylation or methylation via inhibitors by using epigenetic drugs can be a suitable therapeutic approach for a number of diseases. Using the synergistic effects of DNA methylation and histone modification inhibitors, it is hoped that many epigenetic defects will be treated in the future. Numerous studies have demonstrated a link between epigenetic marks and their effects on brain and cancer diseases. Designing appropriate drugs could provide novel strategies for the management of these diseases in the near future. [ABSTRACT FROM AUTHOR]

Application of cost-effective pretreatment of wheat straw is an important stage for massive bioethanol production. A new approach is aimed to enhance the pretreatment of wheat straw by using low-cost ionic liquid [TEA][HSO4] coupled with ultrasound irradiation. The pretreatment was conducted both at room temperature and at 130 °C with a high biomass loading rate of 20% and 20% wt water assisted by ultrasound at 100 W-24 kHz for 15 and 30 min. Wheat straw pretreated at 130 °C for 15 and 30 min had high delignification rates of 67.8% and 74.9%, respectively, and hemicellulose removal rates of 47.0% and 52.2%. Moreover, this pretreatment resulted in producing total reducing sugars of 24.5 and 32.1 mg/mL in enzymatic saccharification, respectively, which corresponds to saccharification yields of 67.7% and 79.8% with commercial cellulase enzyme CelluMax for 72 h. The ethanol generation rates of 38.9 and 42.0 g/L were attained for pretreated samples for 15 and 30 min, equivalent to the yields of 76.1% and 82.2% of the maximum theoretical yield following 48 h of fermentation. This demonstration provided a cheap and promising pretreatment technology in terms of efficiency and shortening the pretreatment time based on applying low-cost ionic liquid and efficient ultrasound pretreatment techniques, which facilitated the feasibility of this approach and could further develop the future of biorefinery. [ABSTRACT FROM AUTHOR]

SiRNA is a new generation of drug molecules and a new approach for treating a variety of diseases such as cancer and viral infections. SiRNA delivery to cells and translocation into cytoplasm are the main challenges in the clinical application of siRNA. Lipid carriers are one of the most successful carriers for siRNA delivery. In this study, we investigated the interaction of siRNA with a zwitterionic bilayer and how ion concentration and lipid conjugation can affect it. The divalent cation such as Mg2+ ions could promote the siRNA adsorption on the bilayer surface. The cation ions can bind to the head groups of lipids and the grooves of siRNA molecules and form bridges between the siRNA and bilayer surface. Our findings demonstrated the bridges formed by divalent ions could facilitate the attachment of siRNA to the membrane surface. We showed that the divalent cations can regulate the bridging-driven membrane attachment and it seems the result of this modulation can be used for designing biomimetic devices. In the following, we examined the effect of cations on the interaction between siRNA modified by cholesterol and the membrane surface. Our MD simulations showed that in the presence of Mg2+, the electrostatic and vdW energy between the membrane and siRNA were higher compared to those in the presence of NA+. We showed that the electrostatic interaction between membrane and siRNA cannot be facilitated only by cholesterol conjugated. Indeed, cations are essential to create coulomb repulsion and enable membrane attachment. This study provides important insight into liposome carriers for siRNA delivery and could help us in the development of siRNA-based therapeutics. Due to the coronavirus pandemic outbreak, these results may shed light on the new approach for treating these diseases and their molecular details. [ABSTRACT FROM AUTHOR]

The simulated liposome models provide events in molecular biological science and cellular biology. These models may help to understand the cell membrane mechanisms, biological cell interactions, and drug delivery systems. In addition, the liposomes model may resolve specific issues such as membrane transports, ion channels, drug penetration in the membrane, vesicle formation, membrane fusion, and membrane protein function mechanism. One of the approaches to investigate the lipid membranes and the mechanism of their formation is by molecular dynamics (MD) simulations. In this study, we used the coarse-grained MD simulation approach and designed a liposome model system. To simulate the liposome model, we used phospholipids that are present in the structure of natural cell membranes (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)). Simulation conditions such as temperature, ions, water, lipid concentration were performed based on experimental conditions. Our results showed a liposome model (ellipse vesicle structure) during the 2100 ns was formed. Moreover, the analysis confirmed that the stretched and ellipse structure is the best structure that could be formed. The eukaryotic and even the bacterial cells have elliptical and flexible structures. Usually, an elliptical structure is more stable than other assembled structures. The results indicated the assembly of the lipids is directed through short-range interactions (electrostatic interactions and, van der Waals interactions). Total energy (Van der Waals and electrostatic interaction energy) confirmed the designed elliptical liposome structure has suitable stability at the end of the simulation process. Our findings confirmed that phospholipids DOPC and DOPE have a good tendency to form bilayer membranes (liposomal structure) based on their geometric shapes and chemical-physical properties. Finally, we expected the simulated liposomal structure as a simple model to be useful in understanding the function and structure of biological cell membranes. Furthermore, it is useful to design optimal, suitable, and biocompatible liposomes as potential drug carriers. [ABSTRACT FROM AUTHOR]

Antimicrobial Peptides (AMPs) have been considered as potential alternatives for infection therapeutics since antibiotic resistance has been raised as a global problem. The AMPs are a group of natural peptides that play a crucial role in the immune system in various organisms AMPs have features such as a short length and efficiency against microbes. Importantly, they have represented low toxicity in mammals which makes them potential candidates for peptide-based drugs. Nevertheless, the discovery of AMPs is accompanied by several issues which are associated with labour-intensive and time-consuming wet-lab experiments. During the last decades, numerous studies have been conducted on the investigation of AMPs, either natural or synthetic type, and relevant data are recently available in many databases. Through the advancement of computational methods, a great number of AMP data are obtained from publicly accessible databanks, which are valuable resources for mining patterns to design new models for AMP prediction. However, due to the current flaws in assessing computational methods, more interrogations are warranted for accurate evaluation/analysis. Considering the diversity of AMPs and newly reported ones, an improvement in Machine Learning algorithms are crucial. In this review, we aim to provide valuable information about different types of AMPs, their mechanism of action and a landscape of current databases and computational tools as resources to collect AMPs and beneficial tools for the prediction and design of a computational model for new active AMPs. [ABSTRACT FROM AUTHOR]

Biomechanical and morphological analysis of the cells is a novel approach for monitoring the environmental features, drugs, and toxic compounds' effects on cells. Graphene oxide (GO) has a broad range of medical applications such as tissue engineering and drug delivery. However, the effects of GO nanosheets on biological systems have not been completely understood. In this study, we focused on the biophysical characteristics of cells and their changes resulting from the effect of GO nanosheets. The biophysical properties of the cell population were characterized as follows: cell stiffness was calculated by atomic force microscopy, cell motility and invasive properties were characterized in the microfluidic chip in which the cells are able to visualize cell migration at a single-cell level. Intracellular actin was stained to establish a quantitative picture of the intracellular cytoskeleton. In addition, to understand the molecular interaction of GO nanosheets and actin filaments, coarse-grained (CG) molecular dynamics (MD) simulations were carried out. Our results showed that GO nanosheets can reduce cell stiffness in MCF7 cells and MDA-MB-231 cell lines and highly inhibited cell migration (39.2%) in MCF-7 and (38.6%) in MDA-MB-231 cell lines through the GO nanosheets-mediated disruption of the intracellular cytoskeleton. In the presence of GO nanosheets, the cell migration of both cell lines, as well as the cell stiffness, significantly decreased. Moreover, after GO nanosheets treatment, the cell actin network dramatically changed. The experimental and theoretical approaches established a quantitative picture of changes in these networks. Our results showed the reduction of the order parameter in actin filaments was 23% in the MCF7 cell line and 20.4% in the MDA-MB-231 cell line. The theoretical studies also showed that the GO nanosheet–actin filaments have stable interaction during MD simulation. Moreover, the 2D free energy plot indicated the GO nanosheet can induce conformational changes in actin filaments. Our findings showed that the GO nanosheets can increase the distance of actin-actin subunits from 3.22 to 3.5 nm and in addition disrupt native contacts between two subunits which lead to separate actin subunits from each other in actin filaments. In this study, the biomechanical characteristics were used to explain the effect of GO nanosheets on cells which presents a novel view of how GO nanosheets can affect the biological properties of cells without cell death. These findings have the potential to be applied in different biomedical applications. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer death in both men and women worldwide. The high mortality rate in lung cancer is in part due to late-stage diagnostics as well as spread of cancer-cells to organs and tissues by metastasis. Automated lung cancer detection and its sub-types classification from cell's images play a crucial role toward an early-stage cancer prognosis and more individualized therapy. The rapid development of machine learning techniques, especially deep learning algorithms, has attracted much interest in its application to medical image problems. In this study, to develop a reliable Computer-Aided Diagnosis (CAD) system for accurately distinguishing between cancer and healthy cells, we grew popular Non-Small Lung Cancer lines in a microfluidic chip followed by staining with Phalloidin and images were obtained by using an IX-81 inverted Olympus fluorescence microscope. We designed and tested a deep learning image analysis workflow for classification of lung cancer cell-line images into six classes, including five different cancer cell-lines (P-C9, SK-LU-1, H-1975, A-427, and A-549) and normal cell-line (16-HBE). Our results demonstrate that ResNet18, a residual learning convolutional neural network, is an efficient and promising method for lung cancer cell-lines categorization with a classification accuracy of 98.37% and F1-score of 97.29%. Our proposed workflow is also able to successfully distinguish normal versus cancerous cell-lines with a remarkable average accuracy of 99.77% and F1-score of 99.87%. The proposed CAD system completely eliminates the need for extensive user intervention, enabling the processing of large amounts of image data with robust and highly accurate results. [ABSTRACT FROM AUTHOR]

The low membrane permeability of lipophilic drugs was resolved using liposomes as a solubilizing agent and the precise size control of them is a significant parameter in drug carrier technology. Here, we have established a microfluidic octanol-assisted liposome assembly method to produce a surfactant-assisted liposome which has merged by the cytoskeleton drug (Taxotere) encapsulation in a single process step, then a complete microfluidic cellular analysis was performed in trapping cell device with an optofluidic assay for quantifying drug permeability. The optimization of process variables resulted in the formation of liposomes with particle size 6.75 ± 0.5 µm and monodispersity 6.2%, representing encapsulation efficiency and loading capacity of 65.49 ± 3.08% and 10.16 ± 0.32%, respectively. Qualitative and quantitative studies of cellular uptake in MCF-7 cell line that was cultured in the cell trapping chip indicated a significant increase in cellular uptake of carboxyfluorescein-loaded liposomes, suggesting endocytic mechanisms. The drug-loaded liposomes with an IC50 value of 0.55 ± 0.04 μg mL−1 have shown a higher level of cellular inhibition and apoptosis in cells than free Taxotere (2.48 ± 0.01). Furthermore, real-time analysis of the dynamic labeling assay for live/dead cells was investigated. Our data revealed that lab-on-a-chip platforms for the time-lapse fluorescence imaging were applied for drug screening routines. Cytoskeleton drugs encapsulated in liposome using microfluidic approaches and investigation of programmed cell death assay. [ABSTRACT FROM AUTHOR]

Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists of methylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation. PTMs have fundamental roles in chromatin structure and function. Histone modifications have also been known as epigenetic markers. The PTMs that have taken place in histone proteins can affect gene expression by altering chromatin structure. Histone modifications act in varied biological processes such as transcriptional activation/inactivation, chromosome packaging, mitosis, meiosis, apoptosis, and DNA damage/repair. Defects in the PTMs pathway have been associated with the occurrence and progression of various human diseases, such as cancer, heart failure, autoimmune diseases, and neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Histone modifications are reversible and used as potential targets for cancer therapy and prevention. Recent different histone PTMs have key roles in cancer cells since it has been shown that histone PTMs markers in cancers are acetylation, methylation, phosphorylation, and ubiquitylation. In this review, we have summarized the six most studied histone modifications and have examined the role of these modifications in the development of cancer. [ABSTRACT FROM AUTHOR]

This study has been focused on the batch culture removal of Cu2+and Ni2+ions from the aqueous solution using marine brown algaeSargassum angustifolium. Influences of parameters like pH, initial metal ions concentration and biosorbent dosage on nickel and copper adsorption were also examined using the Box–Behnken design matrix. For biosorption of Cu2+the optimum pH value was determined as 5.0, optimum biosorbent concentration to 1.0 g/L and optimum initial concentration 0.15 mmol/L. For the biosorption of Ni2+, the optimal condition was the same but the optimum pH value was determined as 6.0. Desorption experiments indicated that CH3COOH and EDTA were efficient desorbents for recovery from Cu2+and Ni2+. The Langmuir isotherm model was applied to describe the biosorption of the Cu2+and Ni2+intoS. angustifolium. The maximum uptake of Cu2+and Ni2+ions by theS. angustifoliumbiomass under the optimal conditions was approximately 0.94 and 0.78 mmol/g dry alga, respectively. Response surface models showed that the data were adequately fitted to a second-order polynomial model. Analysis of variance showed a high coefficient of determination value (R2=0.993 for Cu2+and 0.991 for Ni2+) and a satisfactory second-order regression model was derived. In addition, results reported in this research demonstrated the feasibility of employingS. angustifoliumas biosorbent for Ni2+and Cu2+removal. [ABSTRACT FROM PUBLISHER]

Inadequacy of most animal models for drug efficacy assessments has led to the development of improved in vitro models capable of mimicking in vivo exposure scenarios. Among others, 3D multicellular spheroid technology is considered to be one of the promising alternatives in the pharmaceutical drug discovery process. In addition to its physiological relevance, this method fulfills high-throughput and low-cost requirements for preclinical cell-based assays. Despite the increasing applications of spheroid technology in pharmaceutical screening, its application, in nanotoxicity testing is still in its infancy due to the limited penetration and uptake rates into 3D-cell assemblies. To gain a better understanding of gold nanowires (AuNWs) interactions with 3D spheroids, a comparative study of 2D monolayer cultures and 3D multicellular spheroids was conducted using two lung cancer cell lines (A549 and PC9). Cell apoptosis (live/dead assay), metabolic activity, and spheroid integrity were evaluated following exposure to AuNWs at different dose-time manners. Results revealed a distinct different cellular response between 2D and 3D cell cultures during AuNWs treatment including metabolic rates, cell viability, dose–response curves and, uptake rates. Our data also highlighted further need for more physiologically relevant tissue models to investigate in depth nanomaterial–biology interactions. It is important to note that higher concentrations of AuNWs with lower exposure times and lower concentrations of AuNWs with higher exposure times of 3 days resulted in the loss of spheroid integrity by disrupting cell–cell contacts. These findings could help to increase the understanding of AuNWs-induced toxicity on tissue levels and also contribute to the establishment of new analytical approaches for toxicological and drug screening studies. [ABSTRACT FROM AUTHOR]

Microfluidics cell-based assays require strong cell-substrate adhesion for cell viability, proliferation, and differentiation. The intrinsic properties of PDMS, a commonly used polymer in microfluidics systems, regarding cell-substrate interactions have limited its application for microfluidics cell-based assays. Various attempts by previous researchers, such as chemical modification, plasma-treatment, and protein-coating of PDMS revealed some improvements. These strategies are often reversible, time-consuming, short-lived with either cell aggregates formation, not cost-effective as well as not user- and eco-friendly too. To address these challenges, cell-surface interaction has been tuned by the modification of PDMS doped with different biocompatible nanomaterials. Gold nanowires (AuNWs), superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide sheets (GO), and graphene quantum dot (GQD) have already been coupled to PDMS as an alternative biomaterial enabling easy and straightforward integration during microfluidic fabrication. The synthesized nanoparticles were characterized by corresponding methods. Physical cues of the nanostructured substrates such as Young's modulus, surface roughness, and nanotopology have been carried out using atomic force microscopy (AFM). Initial biocompatibility assessment of the nanocomposites using human amniotic mesenchymal stem cells (hAMSCs) showed comparable cell viabilities among all nanostructured PDMS composites. Finally, osteogenic stem cell differentiation demonstrated an improved differentiation rate inside microfluidic devices. The results revealed that the presence of nanomaterials affected a 5- to 10-fold increase in surface roughness. In addition, the results showed enhancement of cell proliferation from 30% (pristine PDMS) to 85% (nano-modified scaffolds containing AuNWs and SPIONs), calcification from 60% (pristine PDMS) to 95% (PDMS/AuNWs), and cell surface marker expression from 40% in PDMS to 77% in SPION- and AuNWs-PDMS scaffolds at 14 day. Our results suggest that nanostructured composites have a very high potential for stem cell studies and future therapies. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip technology has gained great interest in recent years given its ability to control the spatio-temporal microenvironments of cells and tissues precisely. While physical parameters of the respective niche such as microchannel network sizes, geometric features, flow rates, and shear forces, as well as oxygen tension and concentration gradients, have been optimized for stem cell cultures, little has been done to improve cell-matrix interactions in microphysiological systems. Specifically, detailed research on the effect of matrix elasticity and extracellular matrix (ECM) nanotopography on stem cell differentiation are still in its infancy, an aspect that is known to alter a stem cell's fate. Although a wide range of hydrogels such as gelatin, collagen, fibrin, and others are available for stem cell chip cultivations, only a limited number of elasticities are generally employed. Matrix elasticity and the corresponding nanotopography are key factors that guide stem cell differentiation. Given this, we investigated the addition of gold nanowires into hydrogels to create a tunable biointerface that could be readily integrated into any organ-on-a-chip and cell chip system. In the presented work, we investigated the matrix elasticity (Young's modulus, stiffness, adhesive force, and roughness) and nanotopography of gold nanowire loaded onto fibrin hydrogels using the bio-AFM (atomic force microscopy) method. Additionally, we investigated the capacity of human amniotic mesenchymal stem cells (hAMSCs) to differentiate into osteo- and chondrogenic lineages. Our results demonstrated that nanogold structured-hydrogels promoted differentiation of hAMSCs as shown by a significant increase in Collagen I and II production. Additionally, there was enhanced calcium mineralization activity and proteoglycans formation after a cultivation period of two weeks within microfluidic devices. [ABSTRACT FROM AUTHOR]

This paper presents experimental and numerical investigations of a novel passive micromixer based on the lamination of fluid layers. Lamination-based mixers benefit from increasing the contact surface between two fluid phases by enhancing molecular diffusion to achieve a faster mixing. Novel three-dimensional split and recombine (SAR) structures are proposed to generate fluid laminations. Numerical simulations were conducted to model the mixer performance. Furthermore, experiments were conducted using dyes to observe fluid laminations and evaluate the proposed mixer's characteristics. Mixing quality was experimentally obtained by means of image-based mixing index (MI) measurement. The multi-layer device was fabricated utilizing the Xurography method, which is a simple and low-cost method to fabricate 3D microfluidic devices. Mixing indexes of 96% and 90% were obtained at Reynolds numbers of 0.1 and 1, respectively. Moreover, the device had an MI value of 67% at a Reynolds number of 10 (flow rate of 116 µL/min for each inlet). The proposed micromixer, with its novel design and fabrication method, is expected to benefit a wide range of lab-on-a-chip applications, due to its high efficiency, low cost, high throughput and ease of fabrication. [ABSTRACT FROM AUTHOR]

It is well known that chromatin structure is highly sensitive to the ionic environment. However, the combined effects of a physiologically relevant mixed ionic environment of K+, Mg2+ and Na+, which are the main cations of the cell cytoplasm, has not been systematically investigated. We studied folding and self-association (aggregation) of recombinant 12-mer nucleosome arrays with 177 bp DNA repeat length in solutions of mixtures of K+ and Mg2+ or Na+ and Mg2+. In the presence of Mg2+, the addition of sodium ions promotes folding of array into 30-nm fibres, whereas in mixtures of K+ and Mg2+, potassium ions abrogate folding. We found that self-association of nucleosome arrays in mixed salt solutions is synergistically promoted by Mg2+ and monovalent ions, with sodium being slightly more efficient than potassium in amplifying the self-association. The results highlight the importance of a mixed ionic environment for the compaction of chromatin under physiological conditions and demonstrate the complicated nature of the various factors that determine and regulate chromatin compaction in vivo. [ABSTRACT FROM AUTHOR]