13C metabolic flux analysis (MFA) has become an indispensable tool to measure metabolic reaction rates (fluxes) in living organisms, having an increasingly diverse range of applications. Here, the choice of the13C labeled tracer composition makes the difference between an information-rich experiment and an experiment with only limited insights. To improve the chances for an informative labeling experiment, optimal experimental design approaches have been devised for13C-MFA, all relying on some a priori knowledge about the actual fluxes. If such prior knowledge is unavailable, e.g., for research organisms and producer strains, existing methods are left with a chicken-and-egg problem. In this work, we present a general computational method, termed robustified experimental design (R-ED), to guide the decision making about suitable tracer choices when prior knowledge about the fluxes is lacking. Instead of focusing on one mixture, optimal for specific flux values, we pursue a sampling based approach and introduce a new design criterion, which characterizes the extent to which mixtures are informative in view of all possible flux values. The R-ED workflow enables the exploration of suitable tracer mixtures and provides full flexibility to trade off information and cost metrics. The potential of the R-ED workflow is showcased by applying the approach to the industrially relevant antibiotic producer Streptomyces clavuligerus, where we suggest informative, yet economic labeling strategies.Cancer is considered one of the most predominant diseases in the world and one of the principal causes of mortality per year. The cellular and molecular mechanisms involved in the development and establishment of solid tumors can be defined as tumorigenesis. Recent technological advances in the 3D cell culture field have enabled the recapitulation of tumorigenesis in vitro, including the complexity of stromal microenvironment. The establishment of these 3D solid tumor models has a crucial role in personalized medicine and drug discovery. Recently, spheroids and organoids are being largely explored as 3D solid tumor models for recreating tumorigenesis in vitro. In spheroids, the solid tumor can be recreated from cancer cells, cancer stem cells, stromal and immune cell lineages. Organoids must be derived from tumor biopsies, including cancer and cancer stem cells. Both models are considered as a suitable model for drug assessment and high-throughput screening. The main advantages of 3D bioprinting are its ability to engineer complex and controllable 3D tissue models in a higher resolution. Although 3D bioprinting represents a promising technology, main challenges need to be addressed to improve the results in cancer research. The aim of this review is to explore (1) the principal cell components and extracellular matrix composition of solid tumor microenvironment; (2) the recapitulation of tumorigenesis in vitro using spheroids and organoids as 3D culture models; and (3) the opportunities, challenges, and applications of 3D bioprinting in this area.Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration after injury, interact. https://www.selleckchem.com/products/clozapine-n-oxide.html Recently, in silico techniques provide a unique integrated platform to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration. Here, we introduce a novel integrated Cartilage Adaptive REorientation Degeneration (CARED) algorithm to predict the interaction between degenerative variations in main cartilage constituents, namely collagen fibril disorganization and degradation, proteoglycan (PG) loss, and change in water content. The algorithm iteratively interacts with a finite element (FE) model of a cartilage explant, withboth on the surface and around the lesion. Our results confirm that the cartilage lesion depth is a crucial parameter affecting tissue degeneration, even under physiological loading conditions. The results suggest that potential fibril reorientation might prevent or slow down fibril degradation under conditions in which the tissue mechanical homeostasis is perturbed like the presence of defects or injurious loading.Background and purpose Tumorous lesions developing in the cerebellopontine angle (CPA) get into close contact with the 1st (cisternal) and 2nd (meatal) intra-arachnoidal portion of the facial nerve (FN). When surgical damage occurs, commonly known reconstruction strategies are often associated with poor functional recovery. This article aims to provide a systematic overview for translational research by establishing the current evidence on available clinical studies and experimental models reporting on intracranial FN injury. Methods A systematic literature search of several databases (PubMed, EMBASE, Medline) was performed prior to July 2020. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Included clinical studies were reviewed and categorized according to the pathology and surgical resection strategy, and experimental studies according to the animal. For anatomical study purposes, l and physiological features of the intracranial FN warrant a distinguishment of experimental models for intracranial FN injuries. New Zealand White rabbits might be a very cost-effective and valuable option to test new experimental approaches for intracranial FN regeneration. Flexible and bioactive biomaterials, commonly used in skull base surgery, endowed with trophic and topographical functions, should address the specific needs of intracranial FN injuries.Animal silk-derived carbon materials are of interest to various applications, such as smart cloth and wearable sensors. However, it remains a challenge to massively transform silks into continuous carbon fibers. In this work, carbon fibers based on two kinds of animal silks, i.e., Bombyx mori (B. mori) silk and Antheraea pernyi (A. pernyi) silk, are prepared by using a large-scale-capable one-step heating process without any additives or activation process. These carbon fibers and yarns are electroconductive and mechanically robust. To expand the application of these carbonized silks, we further weaved them with cotton yarns to obtain composite fabrics with different textures and evaluated their performance for solar steam evaporation. Our results confirmed that the advantages of these composite fabrics in light absorption, large surface area, and hierarchical liquid transport channels allowed them to be used as a solar steam generation for desalination and sewage treatment. In addition, we reported that these conductive carbon fibers could be assembled into fluidic nanogenerators to generate electricity from the water flow.
13C metabolic flux analysis (MFA) has become an indispensable tool to measure metabolic reaction rates (fluxes) in living organisms, having an increasingly diverse range of applications. Here, the choice of the13C labeled tracer composition makes the difference between an information-rich experiment and an experiment with only limited insights. To improve the chances for an informative labeling experiment, optimal experimental design approaches have been devised for13C-MFA, all relying on some a priori knowledge about the actual fluxes. If such prior knowledge is unavailable, e.g., for research organisms and producer strains, existing methods are left with a chicken-and-egg problem. In this work, we present a general computational method, termed robustified experimental design (R-ED), to guide the decision making about suitable tracer choices when prior knowledge about the fluxes is lacking. Instead of focusing on one mixture, optimal for specific flux values, we pursue a sampling based approach and introduce a new design criterion, which characterizes the extent to which mixtures are informative in view of all possible flux values. The R-ED workflow enables the exploration of suitable tracer mixtures and provides full flexibility to trade off information and cost metrics. The potential of the R-ED workflow is showcased by applying the approach to the industrially relevant antibiotic producer Streptomyces clavuligerus, where we suggest informative, yet economic labeling strategies.Cancer is considered one of the most predominant diseases in the world and one of the principal causes of mortality per year. The cellular and molecular mechanisms involved in the development and establishment of solid tumors can be defined as tumorigenesis. Recent technological advances in the 3D cell culture field have enabled the recapitulation of tumorigenesis in vitro, including the complexity of stromal microenvironment. The establishment of these 3D solid tumor models has a crucial role in personalized medicine and drug discovery. Recently, spheroids and organoids are being largely explored as 3D solid tumor models for recreating tumorigenesis in vitro. In spheroids, the solid tumor can be recreated from cancer cells, cancer stem cells, stromal and immune cell lineages. Organoids must be derived from tumor biopsies, including cancer and cancer stem cells. Both models are considered as a suitable model for drug assessment and high-throughput screening. The main advantages of 3D bioprinting are its ability to engineer complex and controllable 3D tissue models in a higher resolution. Although 3D bioprinting represents a promising technology, main challenges need to be addressed to improve the results in cancer research. The aim of this review is to explore (1) the principal cell components and extracellular matrix composition of solid tumor microenvironment; (2) the recapitulation of tumorigenesis in vitro using spheroids and organoids as 3D culture models; and (3) the opportunities, challenges, and applications of 3D bioprinting in this area.Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration after injury, interact. https://www.selleckchem.com/products/clozapine-n-oxide.html Recently, in silico techniques provide a unique integrated platform to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration. Here, we introduce a novel integrated Cartilage Adaptive REorientation Degeneration (CARED) algorithm to predict the interaction between degenerative variations in main cartilage constituents, namely collagen fibril disorganization and degradation, proteoglycan (PG) loss, and change in water content. The algorithm iteratively interacts with a finite element (FE) model of a cartilage explant, withboth on the surface and around the lesion. Our results confirm that the cartilage lesion depth is a crucial parameter affecting tissue degeneration, even under physiological loading conditions. The results suggest that potential fibril reorientation might prevent or slow down fibril degradation under conditions in which the tissue mechanical homeostasis is perturbed like the presence of defects or injurious loading.Background and purpose Tumorous lesions developing in the cerebellopontine angle (CPA) get into close contact with the 1st (cisternal) and 2nd (meatal) intra-arachnoidal portion of the facial nerve (FN). When surgical damage occurs, commonly known reconstruction strategies are often associated with poor functional recovery. This article aims to provide a systematic overview for translational research by establishing the current evidence on available clinical studies and experimental models reporting on intracranial FN injury. Methods A systematic literature search of several databases (PubMed, EMBASE, Medline) was performed prior to July 2020. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Included clinical studies were reviewed and categorized according to the pathology and surgical resection strategy, and experimental studies according to the animal. For anatomical study purposes, l and physiological features of the intracranial FN warrant a distinguishment of experimental models for intracranial FN injuries. New Zealand White rabbits might be a very cost-effective and valuable option to test new experimental approaches for intracranial FN regeneration. Flexible and bioactive biomaterials, commonly used in skull base surgery, endowed with trophic and topographical functions, should address the specific needs of intracranial FN injuries.Animal silk-derived carbon materials are of interest to various applications, such as smart cloth and wearable sensors. However, it remains a challenge to massively transform silks into continuous carbon fibers. In this work, carbon fibers based on two kinds of animal silks, i.e., Bombyx mori (B. mori) silk and Antheraea pernyi (A. pernyi) silk, are prepared by using a large-scale-capable one-step heating process without any additives or activation process. These carbon fibers and yarns are electroconductive and mechanically robust. To expand the application of these carbonized silks, we further weaved them with cotton yarns to obtain composite fabrics with different textures and evaluated their performance for solar steam evaporation. Our results confirmed that the advantages of these composite fabrics in light absorption, large surface area, and hierarchical liquid transport channels allowed them to be used as a solar steam generation for desalination and sewage treatment. In addition, we reported that these conductive carbon fibers could be assembled into fluidic nanogenerators to generate electricity from the water flow.
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