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Embryonic stem-like cells (ES-like cells) are promising for medical research and clinical applications. Traditional methods involve "Yamanaka" transcription (OSKM) to derive these cells from somatic cells in vitro. Recently, a novel approach has emerged, obtaining ES-like cells from spermatogonia stem cells (SSCs) in a time-related process without adding artificial additives to cell cultures, like transcription factors or small molecules such as pten or p53 inhibitors. This study aims to investigate the role of the Nanog in the conversion of SSCs to pluripotent stem cells through both in silico analysis and in vitro experiments. We used bioinformatic methods and microarray data to find significant genes connected to this derivation path, to construct PPI networks, using enrichment analysis, and to construct miRNA-lncRNA networks, as well as in vitro experiments, immunostaining, and Fluidigm qPCR analysis to connect the dots of Nanog significance. We concluded that Nanog is one of the most crucial differentially expressed genes during SSC conversion, collaborating with critical regulators such as Sox2, Dazl, Pou5f1, Dnmt3, and Cdh1. This intricate protein network positions Nanog as a pivotal factor in pathway enrichment for generating ES-like cells, including Wnt signaling, focal adhesion, and PI3K-Akt-mTOR signaling. Nanog expression is presumed to play a vital role in deriving ES-like cells from SSCs in vitro. Finding its pivotal role in this path illuminates future research and clinical applications. [ABSTRACT FROM AUTHOR]

Mechanical stimulation is prevalent within organisms, and appropriate regulation of such stimulation can significantly enhance cellular functions. Consequently, the in vitro construction and simulation of mechanical stimulation have emerged as a research hotspot in biomechanics. In recent years, a class of artificial muscles named electroactive polymers (EAPs), especially ionic EAPs, have shown promising applications in biomechanics. While several techniques utilizing ionic EAPs for cell mechanical stimulation have been reported, further research is needed to advance and enhance their practical applications. Here, we prepared a microactuator array based on ionic EAP artificial muscles for cell mechanical stimulation. As a preliminary effort, we created a 5 × 5 microactuator array on a supporting membrane by employing laser cutting. We evaluated the electro-actuation performance of the microactuators through experimental testing and numerical simulations, affirming the potential use of the microactuator array for cell mechanical stimulation. The devised approach could inspire innovative design concepts in the development of miniaturized intelligent electronic devices, not only in biomechanics and biomimetics but also in other related fields. [ABSTRACT FROM AUTHOR]

Excess cortisol release is associated with numerous health concerns, including psychiatric issues (i.e., anxiety, insomnia, and depression) and nonpsychiatric issues (i.e., osteoporosis). The aim of this study was to assess the in vitro inhibition of cortisol release, bioaccessibility, and bioavailability exerted by a chemically characterized Scutellaria lateriflora L. extract (SLE). The treatment of H295R cells with SLE at increasing, noncytotoxic, concentrations (5–30 ng/mL) showed significant inhibition of cortisol release ranging from 58 to 91%. The in vitro simulated gastric, duodenal, and gastroduodenal digestions, induced statistically significant reductions (p < 0.0001) in the bioactive polyphenolic compounds that most represented SLE. Bioavailability studies on duodenal digested SLE, using Caco-2 cells grown on transwell inserts and a parallel artificial membrane permeability assay, indicated oroxylin A glucuronide and oroxylin A were the only bioactive compounds able to cross the Caco-2 cell membrane and the artificial lipid membrane, respectively. The results suggest possible applications of SLE as a food supplement ingredient against cortisol-mediated stress response and the use of gastroresistant oral dosage forms to partially prevent the degradation of SLE bioactive compounds. In vivo studies and clinical trials remain necessary to draw a conclusion on the efficacy and tolerability of this plant extract. [ABSTRACT FROM AUTHOR]

Engineering artificial mechanosensory hair cells offers a promising avenue for developing diverse biosensors spanning applications from biomedicine to underwater sensing. Unfortunately, current artificial sensory hair cells do not have the ability to simultaneously achieve ultrahigh sensitivity with low-frequency threshold detection (e.g., 0.1 Hz). This work aimed to solve this gap by developing an artificial sensory hair cell inspired by the vestibular sensory apparatus, which has such functional capabilities. For device characterization and response testing, the sensory unit was inserted in a 3D printed lateral semicircular canal (LSCC) mimicking the environment of the labyrinth. The sensor was fabricated based on platinum (Pt) thin film which was reinforced by carbon nanofibers (CNFs). A Pi-shaped hair cell sensor was created as the sensing element which was tested under various conditions of simulated head motion. Results reveal the hair cell sensor displayed markedly higher sensitivity compared to other reported artificial hair cell sensors (e.g., 21.47 mV Hz−1 at 60°) and low frequency detection capability, 0.1 Hz < f < 1.5 Hz. Moreover, like the LSCC hair cells in biology, the fabricated sensor was most sensitive in a given plane of rotational motion, demonstrating features of directional sensitivity. [ABSTRACT FROM AUTHOR]

On 25 July 2023, a workshop entitled "Molecular Communication Approaches for Wetware Artificial Life" took place as a satellite event at the international conference ALIFE 2023 (The 2023 Conference on Artificial Life). In this report, we comment on the workshop by focusing on the main theme and the motivations that led us to develop this initiative. In particular, we highlight how recent progress in synthetic biology and in the study of molecular communication from an engineering perspective can be fruitfully joined to provide a powerful platform to develop frontier research lines in "wetware" Artificial Life. The talks presented at the workshop are briefly summarized. This report is, ultimately, an opportunity to promote an emerging field that calls for collaborative efforts of scholars from multiple disciplines, from chemistry to molecular biology, from communication engineering to nanotechnology, and up to those interested in more theoretical aspects about complex artificial systems that mimic natural ones. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is the main cause of human death. Nanomedicine provides a new strategy for the treatment of diverse cancers. Among them, superparamagnetic artificial cell PLGA-Fe3O4 micro/nanocapsules demand great attention due to their excellent properties, such as targeted delivery, magnetic response, and biocompatibility. The aim of this review is to summarize the application of superparamagnetic artificial cells (PLGA-Fe3O4) micro/nanocapsules in cancer drug targeted delivery and their preparation methods, providing insights into the future development of superparamagnetic artificial cells (PLGA nano/microcapsules) for magnetic targeting in cancer treatment. Artificial cells have been extensively used in many fields, such as nanomedicine, biotherapy, blood substitutes, drug delivery, enzyme/gene therapy, cancer therapy, and the COVID-19 vaccine. The unique properties of superparamagnetic Fe3O4 nanoparticles have contributed to increased interest in using superparamagnetic artificial cells (PLGA-Fe3O4 micro/nanocapsules) for targeted therapy. In this review, the preparation methods of Fe3O4 NPs and superparamagnetic artificial cell PLGA-drug-Fe3O4 micro/nanocapsules are discussed. This review also focuses on the recent progress of superparamagnetic PLGA-drug-Fe3O4 micro/nanocapsules as targeted therapeutics. We shall concentrate on the use of superparamagnetic artificial cells in the form of PLGA-drug-Fe3O4 nanocapsules for magnetic hyperthermia/photothermal therapy and cancer therapies, including lung breast cancer and glioblastoma. [ABSTRACT FROM AUTHOR]

We investigated the possibility of using Raman spectroscopy assisted by artificial intelligence methods to identify liver cancer cells and distinguish them from their Non-Tumor counterpart. To this aim, primary liver cells (40 Tumor and 40 Non-Tumor cells) obtained from resected hepatocellular carcinoma (HCC) tumor tissue and the adjacent non-tumor area (negative control) were analyzed by Raman micro-spectroscopy. Preliminarily, the cells were analyzed morphologically and spectrally. Then, three machine learning approaches, including multivariate models and neural networks, were simultaneously investigated and successfully used to analyze the cells' Raman data. The results clearly demonstrate the effectiveness of artificial intelligence (AI)-assisted Raman spectroscopy for Tumor cell classification and prediction with an accuracy of nearly 90% of correct predictions on a single spectrum. [ABSTRACT FROM AUTHOR]

Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic foci in the HNSCC tumor microenvironment. It is suspected that a fraction of the biomolecules released by necrotic cells are damage-associated molecular patterns (DAMPs), which are known to be natural endogenous ligands of Toll-like receptors (TLRs), including, among others, proteins and nucleic acids. However, there has been no direct demonstration that biomolecules released by HNSCC necrotic cells can activate TLRs. Our aim was to investigate whether some of these molecules could behave as agonists of the TLR3, either in vitro or in vivo. We chose a functional approach based on reporter cell exhibiting artificial TLR3 expression and downstream release of secreted alkaline phosphatase. The production of biomolecules activating TLR3 was first investigated in vitro using three HNSCC cell lines subjected to various pronecrotic stimuli (external irradiation, serum starvation, hypoxia and oxidative stress). TLR3 agonists were also investigated in necrotic tumor fluids from five oral cancer patients and three mouse tumor grafts. The release of biomolecules activating TLR3 was demonstrated for all three HNSCC cell lines. External irradiation was the most consistently efficient stimulus, and corresponding TLR3 agonists were conveyed in extracellular vesicles. TLR3-stimulating activity was detected in the fluids from all five patients and three mouse tumor grafts. In most cases, this activity was greatly reduced by RNAse pretreatment or TLR3 blocking antibodies. Our data indicate that TLR3 agonists are consistently present in necrotic fluids from HNSCC cells and mainly made of dsRNA fragments. These endogenous agonists may induce TLR3, which might lead to a protumorigenic effect. Regarding methodological aspects, our study demonstrates that direct investigations—including functional testing—can be performed on necrotic fluids from patient tumors. [ABSTRACT FROM AUTHOR]

The recent and important advances in bottom-up synthetic biology (SB), in particular in the field of the so-called "synthetic cells" (SCs) (or "artificial cells", or "protocells"), lead us to consider the role of wetware technologies in the "Sciences of Artificial", where they constitute the third pillar, alongside the more well-known pillars hardware (robotics) and software (Artificial Intelligence, AI). In this article, it will be highlighted how wetware approaches can help to model life and cognition from a unique perspective, complementary to robotics and AI. It is suggested that, through SB, it is possible to explore novel forms of bio-inspired technologies and systems, in particular chemical AI. Furthermore, attention is paid to the concept of semantic information and its quantification, following the strategy recently introduced by Kolchinsky and Wolpert. Semantic information, in turn, is linked to the processes of generation of "meaning", interpreted here through the lens of autonomy and cognition in artificial systems, emphasizing its role in chemical ones. [ABSTRACT FROM AUTHOR]

In this study, we present a statistical forecasting framework and assess its efficacy using a range of established machine learning algorithms for predicting Particulate Matter (PM) concentrations in the Arctic, specifically in Pallas (FI), Reykjavik (IS), and Tromso (NO). Our framework leverages historical ground measurements and 24 h predictions from nine models by the Copernicus Atmosphere Monitoring Service (CAMS) to provide PM10 predictions for the following 24 h. Furthermore, we compare the performance of various memory cells based on artificial neural networks (ANN), including recurrent neural networks (RNNs), gated recurrent units (GRUs), long short-term memory networks (LSTMs), echo state networks (ESNs), and windowed multilayer perceptrons (MLPs). Regardless of the type of memory cell chosen, our results consistently show that the proposed framework outperforms the CAMS models in terms of mean squared error (MSE), with average improvements ranging from 25% to 40%. Furthermore, we examine the impact of outliers on the overall performance of the model. [ABSTRACT FROM AUTHOR]

Photovoltaic power is a crucial renewable energy source that has the potential to enhance a city's sustainability. However, in order to identify the various issues that may occur during the lifespan of a photovoltaic module, solar module inspection techniques are crucial. One valuable technique that is commonly used is luminescence, which captures silicon emissions. This article focuses on a specific luminescence technique called partial photoluminescence. This technique involves illuminating a specific portion of the solar cell surface and recording the luminescence emission generated in the remaining area. This method has been trialed in a laboratory environment, utilizing infrared LEDs as the excitation source. An analysis of the main parameters that affect the technique is provided, where pictures have been taken under varying exposure times ranging from 50 ms to 400 ms, irradiance levels ranging from 200 W/m2 to 1000 W/m2, and a percentage of illuminated cells ranging from 10% to 40%. Furthermore, the experimental device has been modified to generate images utilizing sunlight as the excitation source. Several pictures of damaged cells were taken under an irradiance range of 340 W/m2 to 470 W/m2. The quality of the partial photoluminescence images is comparable to conventional electroluminescence images, but longer exposure times are required. [ABSTRACT FROM AUTHOR]

Lateral phase separation within lipid bilayer membranes has attracted considerable attention in the fields of biophysics and cell biology. Living cells organize laterally segregated compartments, such as raft domains in an ordered phase, and regulate their dynamic structures under isothermal conditions to promote cellular functions. Model membrane systems with minimum components are powerful tools for investigating the basic phenomena of membrane phase separation. With the use of such model systems, several physicochemical characteristics of phase separation have been revealed. This review focuses on the isothermal triggering of membrane phase separation from a physical point of view. We consider the free energy of the membrane that describes lateral phase separation and explain the experimental results of model membranes to regulate domain formation under isothermal conditions. Three possible regulation factors are discussed: electrostatic interactions, chemical reactions and membrane tension. These findings may contribute to a better understanding of membrane lateral organization within living cells that function under isothermal conditions and could be useful for the development of artificial cell engineering. [ABSTRACT FROM AUTHOR]

Artificial cells are based on dynamic compartmentalized systems. Thus, remodeling of membrane-bound systems, such as giant unilamellar vesicles, is finding applications beyond biological studies, to engineer cell-mimicking structures. Giant unilamellar vesicle fusion is rapidly becoming an essential experimental step as artificial cells gain prominence in synthetic biology. Several techniques have been developed to accomplish this step, with varying efficiency and selectivity. To date, characterization of vesicle fusion has relied on small samples of giant vesicles, examined either manually or by fluorometric assays on suspensions of small and large unilamellar vesicles. Automation of the detection and characterization of fusion products is now necessary for the screening and optimization of these fusion protocols. To this end, we implemented a fusion assay based on fluorophore colocalization on the membranes and in the lumen of vesicles. Fluorescence colocalization was evaluated within single compartments by image segmentation with minimal user input, allowing the application of the technique to high-throughput screenings. After detection, statistical information on vesicle fluorescence and morphological properties can be summarized and visualized, assessing lipid and content transfer for each object by the correlation coefficient of different fluorescence channels. Using this tool, we report and characterize the unexpected fusogenic activity of sodium chloride on phosphatidylcholine giant vesicles. Lipid transfer in most of the vesicles could be detected after 20 h of incubation, while content exchange only occurred with additional stimuli in around 8% of vesicles. [ABSTRACT FROM AUTHOR]

Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers. [ABSTRACT FROM AUTHOR]

Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation of epigenetic mechanisms, including DNA methylation. Our aim was to explore the connections between environmental exposures during gestation with DNA methylation of placental cells, maternal and neonatal buccal cells by applying artificial neural networks (ANNs). A total of 28 mother–infant pairs were enrolled. Data on gestational exposure to adverse environmental factors and on mother health status were collected through the administration of a questionnaire. DNA methylation analyses at both gene-specific and global level were analyzed in placentas, maternal and neonatal buccal cells. In the placenta, the concentrations of various metals and dioxins were also analyzed. Analysis of ANNs revealed that suboptimal birth weight is associated with placental H19 methylation, maternal stress during pregnancy with methylation levels of NR3C1 and BDNF in placentas and mother's buccal DNA, respectively, and exposure to air pollutants with maternal MGMT methylation. Associations were also observed between placental concentrations of lead, chromium, cadmium and mercury with methylation levels of OXTR in placentas, HSD11B2 in maternal buccal cells and placentas, MECP2 in neonatal buccal cells, and MTHFR in maternal buccal cells. Furthermore, dioxin concentrations were associated with placental RELN, neonatal HSD11B2 and maternal H19 gene methylation levels. Current results suggest that exposure of pregnant women to environmental stressors during pregnancy could induce aberrant methylation levels in genes linked to several pathways important for embryogenesis in both the placenta, potentially affecting foetal development, and in the peripheral tissues of mothers and infants, potentially providing peripheral biomarkers of environmental exposure. [ABSTRACT FROM AUTHOR]

Chlamydomonas reinhardtii is a widely used object in studies on green algae concerning both photosynthesis aspects and possible biotechnological approaches. The measurement of the maximum O2 evolution by photosystem II (PSII) in living algal cells in the presence of artificial acceptors is one of the commonly used methods for determining the photosynthetic apparatus state or its change as compared to a control, parent strain, etc., because PSII is the most sensitive component of the thylakoid membrane. The present study shows the need to use low concentrations of 2,6-dichloro-1,4-benzoquinone (DCBQ) paired with potassium ferricyanide (FeCy) for achieving the maximum O2 evolution rate, while a DCBQ concentration above certain threshold results in strong suppression of O2 evolution. The required DCBQ concentration depends on the presence of the cell wall and should be exactly ~0.1 mM or in the range of 0.2–0.4 mM for cells with and without a cell wall, respectively. The inhibition effect is caused, probably, by a higher content of DCBQ in the oxidized form inside cells; this depends on the presence of the cell wall, which influences the efficiency of DCBQ diffusion into and out of the cell, where it is maintained by FeCy in the oxidized state. The possible mechanism of DCBQ inhibition action is discussed. [ABSTRACT FROM AUTHOR]

The cultivation of cells in a favorable artificial environment has become a versatile tool in cellular and molecular biology. Cultured primary cells and continuous cell lines are indispensable in investigations of basic, biomedical, and translation research. However, despite their important role, cell lines are frequently misidentified or contaminated by other cells, bacteria, fungi, yeast, viruses, or chemicals. In addition, handling and manipulating of cells is associated with specific biological and chemical hazards requiring special safeguards such as biosafety cabinets, enclosed containers, and other specialized protective equipment to minimize the risk of exposure to hazardous materials and to guarantee aseptic work conditions. This review provides a brief introduction about the most common problems encountered in cell culture laboratories and some guidelines on preventing or tackling respective problems. [ABSTRACT FROM AUTHOR]

The first results of the physical modeling of positive multistrike lightning formation processes using positively charged artificial thunderstorm cells are presented. Experimental studies have shown a significant influence of the number of thunderstorm cells and groups of model hydrometeors introduced into them on the probability of the initiation of repeated strikes. It was found that with an increased number of cells and groups of model hydrometeors, the probability of the formation of repeated positive discharges increases several times. When the second group of model hydrometeors has been introduced into the artificial thunderstorm cell, or when the number of cells has been increased, the probability of the repeated discharge initiation has increased almost in three and in four times respectively. It has been revealed that, depending on the arrangement of model hydrometeor groups in artificial thundercloud cells, the formation of repeated positive discharges from them may proceed both with the "connection" of the uncharged areas of the lower cell and with the "connection" of the upper cell. The parameters of the first and repeated impulse current pulses between the positively charged cells and the ground were determined. It was found that with an increasing number of model hydrometeor groups, the value of the charge neutralized during the stages of first and repeated discharge formation increases. When forming multistrike positive discharges with the "connection" of the upper artificial thunderstorm cell, 20–30% more cloud charge has been neutralized during the repeated discharge than during the formation of a single positive discharge. It was found that the formation of positive repeated discharges was observed in about half of the cases, and that the radiation power and impulse current amplitude at repeated discharges are higher than at the first discharge. This article discusses some possible reasons for such a ratio between the parameters of the first and repeated discharges. It is assumed that the discovered significant influence of large model hydrometeor groups on the probability of the formation and the characteristics of repeated positive discharges from artificial thunderstorm cells indicate a possible key influence of hail arrays in the thundercloud on the formation of repeated strikes of positive lightning and bipolar lightning. The obtained results show that artificial thunderstorm cells of positive polarity, together with groups of large model hydrometeors, have prospects for physical modeling and the investigation of processes of the formation of positive and bipolar repeated lightning strikes. [ABSTRACT FROM AUTHOR]

Polymers are sustainable and renewable materials that are in high demand due to their excellent properties. Natural and synthetic polymers with high flexibility, good biocompatibility, good degradation rate, and stiffness are widely used for various applications, such as tissue engineering, drug delivery, and microfluidic chip fabrication. Indeed, recent advances in microfluidic technology allow the fabrication of polymeric matrix to construct microfluidic scaffolds for tissue engineering and to set up a well-controlled microenvironment for manipulating fluids and particles. In this review, polymers as materials for the fabrication of microfluidic chips have been highlighted. Successful models exploiting polymers in microfluidic devices to generate uniform particles as drug vehicles or artificial cells have been also discussed. Additionally, using polymers as bioink for 3D printing or as a matrix to functionalize the sensing surface in microfluidic devices has also been mentioned. The rapid progress made in the combination of polymers and microfluidics presents a low-cost, reproducible, and scalable approach for a promising future in the manufacturing of biomimetic scaffolds for tissue engineering. [ABSTRACT FROM AUTHOR]

(D) Functional artificial stem cell niche relies on the stimuli cues (through direct contact or soluble factors secretion) exerted by neighboring cells (e.g., endothelial cells, MSCs, osteocytes, adipocytes, chondrocytes, neural cells, etc.) and from ECM components (collagen fibers, proteoglycans, elastin, etc.). Major key features of stem cells' functions are self-renewal and their capacity for differentiation, allowing for maintain a proper stem cell reservoir as well as producing lineage-committed cells [[1]]. Moreover, improving our understanding of how the niche can regulate stem cell fate may contribute to better cell administration in different disorders as a potential "advanced stem cell therapy" [[15]]. Stem cells within their niche are subjected to various direct or indirect interactions exerted by both neighboring cells (stem cell niche stroma) and ECM-mediated signals, such as those obtained from shear stress and tissue stiffness [[16], [18]]. [Extracted from the article]

Background: The lack of a stable source of hepatocytes is one of major limitations in hepatocyte transplantation and clinical applications of a bioartificial liver. Human embryonic stem cells (hESCs) with a high degree of self-renewal and totipotency are a potentially limitless source of a variety of cell lineages, including hepatocytes. Many techniques have been developed for effective differentiation of hESCs into functional hepatocyte-like cells. However, the application of hESC-derived hepatocyte-like cells (hESC-Heps) in the clinic has been constrained by the low yield of fully differentiated cells, small-scale culture, difficulties in harvesting, and immunologic graft rejection. To resolve these shortcomings, we developed a novel 3D differentiation system involving alginate-microencapsulated spheres to improve current hepatic differentiation, providing ready-to-use hESC-Heps. Methods: In this study, we used alginate microencapsulation technology to differentiate human embryonic stem cells into hepatocyte-like cells (hESC-Heps). Hepatic markers of hESC-Heps were examined by qPCR and Western blotting, and hepatic functions of hESC-Heps were evaluated by indocyanine-green uptake and release, and ammonia removal. Results: The maturity and hepatic functions of the hESC-Heps derived from this 3D system were better than those derived from 2D culture. Hepatocyte-enriched genes, such as HNF4α, AFP, and ALB, were expressed at higher levels in 3D hESC-Heps than in 2D hESC-Heps. 3D hESC-Heps could metabolize indocyanine green and had better capacity to scavenge ammonia. In addition, the 3D sodium alginate hydrogel microspheres could block viral entry into the microspheres, and thus protect hESC-Heps in 3D microspheres from viral infection. Conclusion: We developed a novel 3D differentiation system for differentiating hESCs into hepatocyte-like cells by using alginate microcapsules. [ABSTRACT FROM AUTHOR]

The objective of this review is to ask whether, and how, principles in conservation biology may need to be revisited in light of new knowledge about the power of epigenetics to alter developmental pathways. Importantly, conservation breeding programmes, used widely by zoological parks and aquariums, may appear in some cases to reduce fitness by decreasing animals' abilities to cope when confronted with the 'wild side' of their natural habitats. Would less comfortable captive conditions lead to the selection of individuals that, despite being adapted to life in a captive environment, be better able to thrive if relocated to a more natural environment? While threatened populations may benefit from advanced reproductive technologies, these may actually induce undesirable epigenetic changes. Thus, there may be inherent risks to the health and welfare of offspring (as is suspected in humans). Advanced breeding technologies, especially those that aim to regenerate the rarest species using stem cell reprogramming and artificial gametes, may also lead to unwanted epigenetic modifications. Current knowledge is still incomplete, and therefore ethical decisions about novel breeding methods remain controversial and difficult to resolve. [ABSTRACT FROM AUTHOR]

Background: Time-lapse microscopy imaging is a key approach for an increasing number of biological and biomedical studies to observe the dynamic behavior of cells over time which helps quantify important data, such as the number of cells and their sizes, shapes, and dynamic interactions across time. Label-free imaging is an essential strategy for such studies as it ensures that native cell behavior remains uninfluenced by the recording process. Computer vision and machine/deep learning approaches have made significant progress in this area. Methods: In this review, we present an overview of methods, software, data, and evaluation metrics for the automatic analysis of label-free microscopy imaging. We aim to provide the interested reader with a unique source of information, with links for further detailed information. Results: We review the most recent methods for cell segmentation, event detection, and tracking. Moreover, we provide lists of publicly available software and datasets. Finally, we summarize the metrics most frequently adopted for evaluating the methods under exam. Conclusions: We provide hints on open challenges and future research directions. [ABSTRACT FROM AUTHOR]

The results of the physical modelling of the formation processes of upward discharges from grounded objects in the artificial thunderstorm cell's electric field are presented. We established the considerable influence of the electrode tip's radius on the pulse streamer corona stem's parameters and, subsequently, on the probability of the transformation of the impulse streamer corona first flash's stem into a first stage of upward leader. We determined the diapason of the optimal tip radii for a lightning rod or lightning conductor, which allows for the most probable formation of the first impulse streamer corona, with the parameters providing the best conditions for the upward leader's start, the purpose of which is the lowering of the probability of lightning striking the object under protection. A considerable difference between the electrical characteristics of the first impulse corona flash with and without the streamer–leader transition was established. It was shown that the amplitude of the streamer corona flash current impulse is considerable, but not the main defining factor of the streamer–leader transition. It is established that the charge value of the streamer corona first flash is not a threshold requirement for the formation of the upward leader from a ground object, but only defines the probability of the successful upward leader formation. Based on the analysis of the experimental data received, we suggest that there is a dependency between the probability of upward positive leader formation from the grounded objects and the charge value of the first pulse streamer corona flash for the rod (centered) and rope (elongated) lightning conductors and objects in the electric field of the thundercloud and downward lightning leader. The obtained results can be used for mathematical modelling of the formation processes of upward discharges from grounded objects in the artificial thunderstorm's electric field, as in a natural thunderstorm situation. [ABSTRACT FROM AUTHOR]

A proton exchange membrane fuel cell (PEMFC) is a more environmentally friendly alternative to deliver electric power in various applications, including in the transportation industry. As PEMFC performance characteristics are inherently nonlinear and involved, the prediction of the performance in a given application for different operating conditions is important in order to optimize the efficiency of the system. Thus, modelling using artificial neural networks (ANNs) to predict its performance can significantly improve the capabilities of handling the multi-variable nonlinear performance of the PEMFC. However, further investigation is needed to develop a dynamic model using ANNs to predict the transient behavior of a PEMFC. This paper predicts the dynamic electrical and thermal performance of a PEMFC stack under various operating conditions. The input variables of the PEMFC stack for the analysis consist of the cathode inlet temperature, anode inlet pressure, anode and cathode inlet flow rates, and stack current. The performances of the ANN models using three different learning algorithms are determined based on the stack voltage and temperature, which have been shown to be consistently predicted by most of these models. Almost all models with varying hidden neurons have coefficients of determination of 0.9 or higher and mean squared errors of less than 5. Thus, the results show promise for dynamic modelling approaches using ANNs for the development of optimal operation of a PEMFC in various system applications. [ABSTRACT FROM AUTHOR]

The development of auditory sensors and systems is essential in smart materials of robotics and is placed at the strategic category of mutual communication between humans and robots. We designed prototypes of the rubber-made equilibrium and auditory sensors, mimicking hair cells in the saccule and the cochlea at the vestibule of the human ear by utilizing our previously proposed technique of electrolytic polymerization on the hybrid fluid rubber (HF rubber). The fabricated artificial hair cells embedded with mimicked free nerve endings and Pacinian corpuscles, which are well-known receptors in the human skin and have already been elucidated effective in the previous study, have the intelligence of equilibrium and auditory sensing. Moreover, they have a voltage that is generated from built-in electricity caused by the ionized particles and molecules in the HF rubber due to piezoelectricity. We verified the equilibrium and auditory characteristics by measuring the changes in voltage with inclination, vibration over a wide frequency range, and sound waves. We elucidated experimentally that the intelligence has optimum morphological conditions. This work has the possibility of advancing the novel technology of state-of-the-art social robotics. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) include a heterogeneous group of natural cell-derived nanostructures that are increasingly regarded as promising biotherapeutic agents and drug delivery vehicles in human medicine. Desirable intrinsic properties of EVs including the ability to bypass natural membranous barriers and to deliver their unique biomolecular cargo to specific cell populations position them as fiercely competitive alternatives for currently available cell therapies and artificial drug delivery platforms. EVs with distinct characteristics can be released from various cell types into the extracellular environment as a means of transmitting bioactive components and altering the status of the target cell. Despite the existence of a large number of preclinical studies confirming the therapeutic efficacy of different originated EVs for treating several pathological conditions, in this review, we first provide a brief overview of EV biophysical properties with an emphasis on their intrinsic therapeutic benefits over cell-based therapies and synthetic delivery systems. Next, we describe in detail different EVs derived from distinct cell sources, compare their advantages and disadvantages, and recapitulate their therapeutic effects on various human disorders to highlight the progress made in harnessing EVs for clinical applications. Finally, knowledge gaps and concrete hurdles that currently hinder the clinical translation of EV therapies are debated with a futuristic perspective. [ABSTRACT FROM AUTHOR]

Atractylodes macrocephala Koidz. is primarily used as a raw material in herbal medicine to treat digestive diseases. To improve the functionality of A. macrocephala, its growth patterns under artificial light were studied. A. macrocephala grew better under MEL light, with the highest chlorophyll content (57.07 ± 0.65 SPAD), than under other artificial light sources. The DPPH free radical scavenging activity of 2000 μg·mL−1 underground extract treated with LED-red light was the highest (95.3 ± 1.1%). Furthermore, the total phenol and flavonoid contents of underground extract treated with LED-green light were the highest at 24.93 ± 0.3 mg GAE·g−1 and 11.2 ± 0.3 mg QE·g−1, respectively. Moreover, in the analysis of whitening activity, the tyrosinase inhibition rate of 5000 μg·mL −1 extract treated with LED-red light was the highest (84.6 ± 2.9%). In anti-inflammatory activity assay, LPS- induced RAW 264.7 cells exposed to 100 μg·mL−1 extract treated with fluorescent light showed the lowest NO levels (2.97 ± 0.14%). Finally, the expression of iNOS and COX-2, which are related to anti-inflammatory activity, was suppressed in cells exposed to artificial light-treated extract compared with that in controls, indicating potent anti-inflammatory activity. Therefore, growth under artificial light can improve the various biological functions of A. macrocephala. [ABSTRACT FROM AUTHOR]

The understanding of the shape-change dynamics leading to the budding and division of artificial cells has gained much attention in the past few decades due to an increased interest in designing stimuli-responsive synthetic systems and minimal models of biological self-reproduction. In this respect, membranes and their composition play a fundamental role in many aspects related to the stability of the vesicles: permeability, elasticity, rigidity, tunability and response to external changes. In this review, we summarise recent experimental and theoretical work dealing with shape deformation and division of (giant) vesicles made of phospholipids and/or fatty acids membranes. Following a classic approach, we divide the strategies used to destabilise the membranes into two different types, physical (osmotic stress, temperature and light) and chemical (addition of amphiphiles, the addition of reactive molecules and pH changes) even though they often act in synergy when leading to a complete division process. Finally, we review the most important theoretical methods employed to describe the equilibrium shapes of giant vesicles and how they provide ways to explain and control the morphological changes leading from one equilibrium structure to another. [ABSTRACT FROM AUTHOR]

Nano- and micrometer-sized compartments composed of synthetic polymers are designed to mimic spatial and temporal divisions found in nature. Self-assembly of polymers into compartments such as polymersomes, giant unilamellar vesicles (GUVs), layer-by-layer (LbL) capsules, capsosomes, or polyion complex vesicles (PICsomes) allows for the separation of defined environments from the exterior. These compartments can be further engineered through the incorporation of (bio)molecules within the lumen or into the membrane, while the membrane can be decorated with functional moieties to produce catalytic compartments with defined structures and functions. Nanometer-sized compartments are used for imaging, theranostic, and therapeutic applications as a more mechanically stable alternative to liposomes, and through the encapsulation of catalytic molecules, i.e., enzymes, catalytic compartments can localize and act in vivo. On the micrometer scale, such biohybrid systems are used to encapsulate model proteins and form multicompartmentalized structures through the combination of multiple compartments, reaching closer to the creation of artificial organelles and cells. Significant progress in therapeutic applications and modeling strategies has been achieved through both the creation of polymers with tailored properties and functionalizations and novel techniques for their assembly. [ABSTRACT FROM AUTHOR]

The airway epithelium of children with asthma is characterized by aberrant repair that may be therapeutically modifiable. The development of epithelial-targeting therapeutics that enhance airway repair could provide a novel treatment avenue for childhood asthma. Drug discovery efforts utilizing high-throughput live cell imaging of patient-derived airway epithelial culture-based wound repair assays can be used to identify compounds that modulate airway repair in childhood asthma. Manual cell tracking has been used to determine cell trajectories and wound closure rates, but is time consuming, subject to bias, and infeasible for high-throughput experiments. We therefore developed software, EPIC, that automatically tracks low-resolution low-framerate cells using artificial intelligence, analyzes high-throughput drug screening experiments and produces multiple wound repair metrics and publication-ready figures. Additionally, unlike available cell trackers that perform cell segmentation, EPIC tracks cells using bounding boxes and thus has simpler and faster training data generation requirements for researchers working with other cell types. EPIC outperformed publicly available software in our wound repair datasets by achieving human-level cell tracking accuracy in a fraction of the time. We also showed that EPIC is not limited to airway epithelial repair for children with asthma but can be applied in other cellular contexts by outperforming the same software in the Cell Tracking with Mitosis Detection Challenge (CTMC) dataset. The CTMC is the only established cell tracking benchmark dataset that is designed for cell trackers utilizing bounding boxes. We expect our open-source and easy-to-use software to enable high-throughput drug screening targeting airway epithelial repair for children with asthma. [ABSTRACT FROM AUTHOR]

Solid Oxide Cells (SOCs) are under intensive development due to their great potential to meet the 2030 targets for decarbonization. One of their advantages is that they can work in reversible mode. However, in respect to durability, there are still some technical challenges. Although the quick development of experimental and modeling approaches gives insight into degradation mechanisms, an obligatory step that cannot be avoided is the performance of long-term tests. Taking into account the target for a commercial lifetime is 80,000 h, experiments lasting years are not acceptable for market needs. This work aims to develop accelerated stress tests (ASTs) for SOCs by the artificial aging of the fuel electrode via redox cycling, which follows the degradation processes of calendar aging (Ni coarsening and migration). However, it can cause irreversible damage by the formation of cracks at the interface anode/electrolyte. The advantages of the developed procedure are that it offers a mild level of oxidation, which can be governed and regulated by the direct impedance monitoring of the Ni network resistance changes during oxidation/reduction on a bare anode sample. Once the redox cycling conditions are fixed and the anode/electrolyte sample is checked for cracks, the procedure is introduced for the AST in full-cell configuration. The developed methodology is evaluated by a comparative analysis of current voltage and impedance measurements of pristine, artificially aged, and calendar-aged button cells, combined with microstructural characterization of their anodes. It can be applied in both fuel cell and electrolyzer mode. The results obtained in this study from the electrochemical tests show that the artificially aged experimental cell corresponds to at least 3500 h of nominal operation. The number of hours is much bigger in respect to the microstructural aging of the anode. Taking into consideration that the duration of the performed 20 redox cycles is about 50 to 60 working hours, the acceleration factor in respect to experimental timing is estimated to be higher than 60, without any damaging of the sample. This result shows that the selected approach is very promising for a large decrease in testing times for SOCs. [ABSTRACT FROM AUTHOR]

The Hubel–Wiesel (HW) model is a classical neurobiological model for explaining the orientation selectivity of cortical cells. However, the HW model still has not been fully proved physiologically, and there are few concise but efficient systems to quantify and simulate the HW model and can be used for object orientation detection applications. To realize a straightforward and efficient quantitive method and validate the HW model's reasonability and practicality, we use McCulloch-Pitts (MP) neuron model to simulate simple cells and complex cells and implement an artificial visual system (AVS) for two-dimensional object orientation detection. First, we realize four types of simple cells that are only responsible for detecting a specific orientation angle locally. Complex cells are realized with the sum function. Every local orientation information of an object is collected by simple cells and subsequently converged to the corresponding same type complex cells for computing global activation degree. Finally, the global orientation is obtained according to the activation degree of each type of complex cell. Based on this scheme, an AVS for global orientation detection is constructed. We conducted computer simulations to prove the feasibility and effectiveness of our scheme and the AVS. Computer simulations show that the mechanism-based AVS can make accurate orientation discrimination and shows striking biological similarities with the natural visual system, which indirectly proves the rationality of the Hubel–Wiesel model. Furthermore, compared with traditional CNN, we find that our AVS beats CNN on orientation detection tasks in identification accuracy, noise resistance, computation and learning cost, hardware implementation, and reasonability. [ABSTRACT FROM AUTHOR]

In fact, due to their characteristics, stem cells from different sources are now considered promising candidates for cell replacement therapies, as well as for drug screening applications and developmental biology studies [[5]]. Stem Cell Rep. 2016; 2: 73-84. 10.1007/s40778-016-0035-7. 29445585 7 Barhouse P.S., Andrade M.J., Smith Q. Home Away From Home: Bioengineering Advancements to Mimic the Developmental and Adult Stem Cell Niche. The term "cellular microenvironment" is a generic expression used to describe the complex collection of stimuli that contribute to cell and tissue functions [[1]]. Other stimuli, more physical in nature, include cell-cell interactions and interactions between cells and components of the extracellular matrix. [Extracted from the article]

The anterior segment of the eye is a complex set of structures that collectively act to maintain the integrity of the globe and direct light towards the posteriorly located retina. The eye is exposed to numerous physical and environmental insults such as infection, UV radiation, physical or chemical injuries. Loss of transparency to the cornea or lens (cataract) and dysfunctional regulation of intra ocular pressure (glaucoma) are leading causes of worldwide blindness. Whilst traditional therapeutic approaches can improve vision, their effect often fails to control the multiple pathological events that lead to long-term vision loss. Regenerative medicine approaches in the eye have already had success with ocular stem cell therapy and ex vivo production of cornea and conjunctival tissue for transplant recovering patients' vision. However, advancements are required to increase the efficacy of these as well as develop other ocular cell therapies. One of the most important challenges that determines the success of regenerative approaches is the preservation of the stem cell properties during expansion culture in vitro. To achieve this, the environment must provide the physical, chemical and biological factors that ensure the maintenance of their undifferentiated state, as well as their proliferative capacity. This is likely to be accomplished by replicating the natural stem cell niche in vitro. Due to the complex nature of the cell microenvironment, the creation of such artificial niches requires the use of bioengineering techniques which can replicate the physico-chemical properties and the dynamic cell-extracellular matrix interactions that maintain the stem cell phenotype. This review discusses the progress made in the replication of stem cell niches from the anterior ocular segment by using bioengineering approaches and their therapeutic implications. [ABSTRACT FROM AUTHOR]

J. Syst. Chem. 2011; 2: 1. 10.1186/1759-2208-2-1 6 Fiore M., Madanamoothoo W., Berlioz-Barbier A., Maniti O., Girard-Egrot A., Buchet R., Strazewski P. Giant vesicles from rehydrated crude mixtures containing unexpected mixtures of amphiphiles formed under plausibly prebiotic conditions. 10.1073/pnas.2012170118 11 Lopez A., Fiore M. Investigating Prebiotic Protocells for a Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective. The Seminal Idea of Systems Chemistry and the Bottom-Up Approach The main purpose of synthetic chemistry is the preparation of pure, designed compounds by using well-defined synthetic pathways and multi-step reactions. [Extracted from the article]

The recapitulation of the stem cell microenvironment is an emerging area of research that has grown significantly in the last 10 to 15 years. Being able to understand the underlying mechanisms that relate stem cell behavior to the physical environment in which stem cells reside is currently a challenge that many groups are trying to unravel. Several approaches have attempted to mimic the biological components that constitute the native stem cell niche, however, this is a very intricate environment and, although promising advances have been made recently, it becomes clear that new strategies need to be explored to ensure a better understanding of the stem cell niche behavior. The second strand in stem cell niche research focuses on the use of manufacturing techniques to build simple but functional models; these models aim to mimic the physical features of the niche environment which have also been demonstrated to play a big role in directing cell responses. This second strand has involved a more engineering approach in which a wide set of microfabrication techniques have been explored in detail. This review aims to summarize the use of these microfabrication techniques and how they have approached the challenge of mimicking the native stem cell niche. [ABSTRACT FROM AUTHOR]

Membranes are important components in a number of systems, where separation and control of the flow of molecules is desirable. Controllable membranes represent an even more coveted and desirable entity and their development is considered to be the next step of development. Typically, membranes are considered on flat surfaces, but spherical capsules possess a perfect "infinite" or fully suspended membranes. Similarities and transitions between spherical and flat membranes are discussed, while applications of membranes are also emphasized. [ABSTRACT FROM AUTHOR]

The multifaceted role of biological membranes prompted early the development of artificial lipid-based models with a primary view of reconstituting the natural functions in vitro so as to study and exploit chemoreception for sensor engineering. Over the years, a fair amount of knowledge on the artificial lipid membranes, as both, suspended or supported lipid films and liposomes, has been disseminated and has helped to diversify and expand initial scopes. Artificial lipid membranes can be constructed by several methods, stabilized by various means, functionalized in a variety of ways, experimented upon intensively, and broadly utilized in sensor development, drug testing, drug discovery or as molecular tools and research probes for elucidating the mechanics and the mechanisms of biological membranes. This paper reviews the state-of-the-art, discusses the diversity of applications, and presents future perspectives. The newly-introduced field of artificial cells further broadens the applicability of artificial membranes in studying the evolution of life. [ABSTRACT FROM AUTHOR]

The current review focuses on vesicles obtained from the self-assembly of two types of dendritic macromolecules, namely amphiphilic Janus dendrimers (forming dendrimersomes) and amphiphilic dumbbells. In the first part, we will present some synthetic strategies and the various building blocks that can be used to obtain dendritic-based macromolecules, thereby showing their structural versatility. We put our focus on amphiphilic Janus dendrimers and amphiphilic dumbbells that form vesicles in water but we also encompass vesicles formed thereof in organic solvents. The second part of this review deals with the production methods of these vesicles at the nanoscale but also at the microscale. Furthermore, the influence of various parameters (intrinsic to the amphiphilic JD and extrinsic-from the environment) on the type of vesicle formed will be discussed. In the third part, we will review the numerous biomedical applications of these vesicles of nano- or micron-size. [ABSTRACT FROM AUTHOR]

Acaricidal nylon 66 fabrics (AN66Fs) grafted with clove oil-loaded microcapsules (COMCs) were developed against Dermatophagoides farina (D. gallinae). The average diameter was about 2.9 μm with a range of 100 nm-8.5 μm. COMCs carried clove oil loading of about 65 vol %. COMCs were chemically grafted to electrospun nylon nanofibers by the chemical reactions between -OH groups of COMCs and -COOH end groups of nylon fabrics to form ester linkages. AN66Fs had an effect on D. farinae depending on COMCs loadings. The increase in COMCs loading of AN66Fs from 5 to 15 wt % increased from 22% to 93% mortality against D. farinae within 72 h. However, AN66Fs containing over 20 wt % COMCs were more effective, showing up to 100% mortality within 24 h because the large amount of monoterpene alcohol, eugenol. This research suggests the use of clove oil and its major constituent eugenol as eco-friendly bioactive agents that can serve as a replacement for synthetic acaricides in controlling the population of D. farinae. [ABSTRACT FROM AUTHOR]

Recent progress in the development of phenylboronic acid (PBA)-functionalized layer-by-layer (LbL) assemblies and their biomedical applications was reviewed. Stimuli-sensitive LbL films and microcapsules that exhibit permeability changes or decompose in response to sugars and hydrogen peroxide (H2O2) have been developed using PBA-bearing polymers. The responses of PBA-modified LbL assemblies arise from the competitive binding of sugars to PBA in the films or oxidative decomposition of PBA by H2O2. Electrochemical glucose sensors have been fabricated by coating the surfaces of electrodes by PBA-modified LbL films, while colorimetric and fluorescence sensors can be prepared by modifying LbL films with boronic acid-modified dyes. In addition, PBA-modified LbL films and microcapsules have successfully been used in the construction of drug delivery systems (DDS). Among them, much effort has been devoted to the glucose-triggered insulin delivery systems, which are constructed by encapsulating insulin in PBA-modified LbL films and microcapsules. Insulin is released from the PBA-modified LbL assemblies upon the addition of glucose resulting from changes in the permeability of the films or decomposition of the film entity. Research into insulin DDS is currently focused on the development of high-performance devices that release insulin in response to diabetic levels of glucose (>10 mM) but remain stable at normal levels (~5 mM) under physiological conditions. [ABSTRACT FROM AUTHOR]

Self-healing cementitious materials containing a microencapsulated healing agent are appealing due to their great application potential in improving the serviceability and durability of concrete structures. In this study, poly(phenol-formaldehyde) (PF) microcapsules that aim to provide a self-healing function for cementitious materials were prepared by an in situ polymerization reaction. Size gradation of the synthesized microcapsules was achieved through a series of sieving processes. The shell thickness and the diameter of single microcapsules was accurately measured under environmental scanning electron microscopy (ESEM). The relationship between the physical properties of the synthesized microcapsules and their micromechanical properties were investigated using nanoindentation. The results of the mechanical tests show that, with the increase of the mean size of microcapsules and the decrease of shell thickness, the mechanical force required to trigger the self-healing function of microcapsules increased correspondingly from 68.5 ± 41.6 mN to 198.5 ± 31.6 mN, featuring a multi-sensitive trigger function. Finally, the rupture behavior and crack surface of cement paste with embedded microcapsules were observed and analyzed using X-ray computed tomography (XCT). The synthesized PF microcapsules may find potential application in self-healing cementitious materials. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the self-healing behaviors of bitumen using microcapsules containing rejuvenator by a modified fracture healing–refracture method through a repetitive tension test. Microcapsules had mean size values of 10, 20 and 30 μm with a same core/shell ratio of 1/1. Various microcapsules/bitumen samples were fabricated with microcapsule contents of 1.0, 3.0 and 5.0 wt. %, respectively. Tension strength values of microcapsules/bitumen samples were measured by a reparative fracture-healing process under different temperatures. It was found that these samples had tensile strength values larger than the data of pure bitumen samples under the same conditions after the four tensile fracture-healing cycles. Fracture morphology investigation and mechanism analysis indicated that the self-healing process was a process consisting of microcapsules being broken, penetrated and diffused. Moreover, the crack healing of bitumen can be considered as a viscosity driven process. The self-healing ability partly repaired the damage of bitumen during service life by comparing the properties of virgin and rejuvenated bitumen. [ABSTRACT FROM AUTHOR]

The existence of orderly structures, such as tissues and organs is made possible by cell adhesion, i.e., the process by which cells attach to neighbouring cells and a supporting substance in the form of the extracellular matrix. The extracellular matrix is a three-dimensional structure composed of collagens, elastin, and various proteoglycans and glycoproteins. It is a storehouse for multiple signalling factors. Cells are informed of their correct connection to the matrix via receptors. Tissue disruption often prevents the natural reconstitution of the matrix. The use of appropriate implants is then required. This review is a compilation of crucial information on the structural and functional features of the extracellular matrix and the complex mechanisms of cell–cell connectivity. The possibilities of regenerating damaged tissues using an artificial matrix substitute are described, detailing the host response to the implant. An important issue is the surface properties of such an implant and the possibilities of their modification. [ABSTRACT FROM AUTHOR]

Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes using genetically engineered encapsulated cells are discussed here: the chronic administration of monoclonal antibodies for passive immunization against neurodegenerative diseases and the local delivery of a cytokine as an adjuvant for anti-cancer vaccines. [ABSTRACT FROM AUTHOR]

The cellular form, manifesting as a membrane-bounded system (comprising various functional molecules), is essential to life. The ultimate reason for this is that, typically, one functional molecule can only adopt one "correct" structure to perform one special function (e.g., an enzyme), and thus molecular cooperation is inevitable. While this is particularly true for advanced life with complex functions, it should have already been true for life at its outset with only limited functions, which entailed some sort of primitive cellular form--"protocells". At the very beginning, the protocells may have even been unable to intervene in the growth of their own membrane, which can be called "pseudo-protocells". Then, the ability to synthesize membrane components (amphiphiles) may have emerged under selective pressure, leading to "true-protocells". The emergence of a "chromosome" (with genes linked together)--thus avoiding "gene-loss" during the protocell division, was another key event in the evolution of protocells. Such "unitary-protocells", containing a central genetic molecule, may have appeared as a milestone--in principle, since then life could evolve endlessly, "gaining" more and more functions by introducing new genes. To synthesize in laboratory these different types of protocells, which stand at the interface between life and non-life, would greatly enhance our understanding on the essence of life. [ABSTRACT FROM AUTHOR]

Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) biological membranes that serve as protective barriers, while allowing communication between the cells and the environment; (2) transcription and translation machinery that synthesize proteins based on genetic sequences; and (3) genetic modules that control the dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells can be used as biomimetic systems to study and understand natural dynamics of cells with minimal interference from cellular complexity. However, there remain significant gaps between artificial and natural cells. How much information can we encode into artificial cells? What is the minimal number of factors that are necessary to achieve robust functioning of artificial cells? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide or even evolve? Here, we review synthetic biological methods that could shrink the gaps between artificial and natural cells. The closure of these gaps will lead to advancement in synthetic biology, cellular biology and biomedical applications. [ABSTRACT FROM AUTHOR]

Over the past few decades, several protocell models have been developed that mimic certain essential characteristics of living cells. These protocells tend to be highly reductionist simplifications of living cells with prominent bilayer membrane boundaries, encapsulated metabolisms and/or encapsulated biologically-derived polymers as potential sources of information coding. In parallel with this conventional work, a novel protocell model based on droplets is also being developed. Such water-in-oil and oil-in-water droplet systems can possess chemical and biochemical transformations and biomolecule production, self-movement, self-division, individuality, group dynamics, and perhaps the fundamentals of intelligent systems and evolution. Given the diverse functionality possible with droplets as mimics of living cells, this system has the potential to be the first true embodiment of artificial life that is an orthologous departure from the one familiar type of biological life. This paper will synthesize the recent activity to develop droplets as protocell models. [ABSTRACT FROM AUTHOR]

Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulated real-world evidence and the barriers associated with applying clinical trials to clinical practices from the perspective of the quality and technical aspects. After providing an overview of all the moving parts involved in the production of CAR-T-cell products, we discuss the characteristics of immune cells (given that T cells are the raw materials for CAR-T-cell therapy) and elucidate the relationship between lifestyle, including diet and exercise, and immune cells. Finally, we briefly highlight future trends in the development of immune cell therapy. These advancements may help position CAR-T-cell therapy as a standard of care. [ABSTRACT FROM AUTHOR]