The availability of L-arginine in tumours is a key determinant of an efficient anti-tumour T cell response
. Consequently, increases of typically low L-arginine concentrations within the tumour may ...greatly potentiate the anti-tumour responses of immune checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1)-blocking antibodies
. However, currently no means are available to locally increase intratumoural L-arginine levels. Here we used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumours and continuously converts ammonia, a metabolic waste product that accumulates in tumours
, to L-arginine. Colonization of tumours with these bacteria increased intratumoural L-arginine concentrations, increased the number of tumour-infiltrating T cells and had marked synergistic effects with PD-L1 blocking antibodies in the clearance of tumours. The anti-tumour effect of these bacteria was mediated by L-arginine and was dependent on T cells. These results show that engineered microbial therapies enable metabolic modulation of the tumour microenvironment leading to enhanced efficacy of immunotherapies.
Pesticide impacts are usually discussed in the context of applied amounts while disregarding the large but environmentally relevant variations in substance-specific toxicity. Here, we systemically ...interpret changes in the use of 381 pesticides over 25 years by considering 1591 substance-specific acute toxicity threshold values for eight nontarget species groups. We find that the toxicity of applied insecticides to aquatic invertebrates and pollinators has increased considerably-in sharp contrast to the applied amount-and that this increase has been driven by highly toxic pyrethroids and neonicotinoids, respectively. We also report increasing applied toxicity to aquatic invertebrates and pollinators in genetically modified (GM) corn and to terrestrial plants in herbicide-tolerant soybeans since approximately 2010. Our results challenge the claims of a decrease in the environmental impacts of pesticide use.
In keeping with emerging consumer trends, the food industry is continually searching for cheaper and healthier protein ingredients to replace those derived from animal sources (e.g., whey, casein, ...gelatin, and ovalbumin), gluten-based proteins (e.g., wheat), and soy. Pea protein shows promise in filling this niche because it is non-genetically modified organism (GMO), gluten-free, nutritious, and of low allergenicity. This review discusses structure-function relationships of pea protein isolates, the impact of extraction techniques used to produce the isolate, and the impact of cultivar and environment on ingredient performance in terms of solubility, water- and oil-holding capacities, emulsifying, foaming, and gelation properties.
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•Ultrafast DES pretreatment was developed for deconstructing the compact cell wall.•Transgenic poplars have low “biomass recalcitrance” as compared to control group.•Structural ...changes of lignin during the DES pretreatment were fully investigated.•The regenerated DES lignin fractions exhibited excellent antioxidant properties.•Enzymatic saccharification of the pretreated substrates was observably elevated.
Reducing the “biomass recalcitrance” and simultaneously improving the efficiency of deconstruction and conversion is vitally important in a biorefinery process. Herein, a microwave-assisted deep eutectic solvents (DES) pretreatment was developed to deconstruct the control and transgenic (C3H, HCT and C3H + HCT co-inhibition) poplars, and improve the lignin extractability and valorization. NMR and GPC results showed that native lignin (Double Enzymatic Lignin, DEL) in different poplars exhibited slightly different structural characteristics, affecting the subsequent lignin extractability and value-added applications. After two kinds of DES (ethylene glycol-based and glycerol-based DES) pretreatments, the yield of DES lignin was obviously increased to 45.38–53.09 % and 46.38–54.30 % in transgenic poplar woods as compared to control poplar wood (37.25 and 38.86 %). In addition, molecular weight, and abundances of different linkages (β-O-4, β-β, β-5, etc.) in the DES lignin fractions were significantly decreased, suggesting the microwave-assisted DES pretreatment has a strong deconstruction ability towards to poplar wood. Moreover, the rapid and efficient pretreatment facilitated the isolation of the lignin fractions from transgenic poplars, and the regenerated DES lignin fractions exhibited excellent antioxidant properties, which will lay the foundation for the lignin valorization. Furthermore, the enzymatic saccharification ratios of the DES pretreated substrates were significantly increased to 87.36–96.55 % in control and transgenic poplar woods, indicating that microwave-assisted DES pretreatment indeed boosted cellulose bioconversion. In short, the combination of genetic modification and DES pretreatment can significantly reduce the “biomass recalcitrance” and promote the biomass valorization.
The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and ...resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a 'signalling-precursor' concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function.
The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their ...capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.
Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon-out of up to 6 synonyms-to encode each amino acid. Synonymous codon choice has diverse and ...important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of Escherichia coli with a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme-with simple corrections at just seven positions-to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA.
Introduction: Cancer disease is known due to its unregulated proliferation of cells that have evolved from the body's regular cells. The disease develops as a result of epigenetic and genetic ...modifications, tumor suppressor gene inactivation, and oncogene activation. The present work describes an environmentally benign approach for the synthesis of manganese oxide nanoparticles (MnO.sub.2 NPs) using Gmelina arborea fruit extract (GAE) in an aqueous medium. Methods: The study evaluated the formation of MnO.sub.2 NPs and their anticancer efficacy against MCF-7 breast cancer cell line. Results: The formation of MnO.sub.2 NPs was confirmed through powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared MnO.sub.2 NPs was evident from XRD pattern. The morphology of the material was studied using SEM analysis, which suggested a rod-like nature with an average diameter of 50 nm. Further, the TEM and HR-TEM images confirmed the rod shape of the as-prepared MnO.sub.2 NPs with an interplanar distance of 0.271 nm. In addition, the concentric rings from selected area electron diffraction (SAED) analysis show the crystalline nature of the as-prepared material, which further supports the obtained XRD pattern. The anticancer efficacy of MnO.sub.2 NPs was evaluated against MCF-7 breast cancer cell line, which showed up to 96% inhibition of the cells at 400 microg/mL concentration. Conclusion: Bio-conjugation of MnO.sub.2 NPs can provide enough scope for the therapeutic use of Gmelina arborea, assuming appropriate mechanistic evaluations are conducted. Keywords: Gmelina arborea, MnO.sub.2 NPs, HR-TEM, MCF-7
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