Synthetic biology approaches for enhancing safety and specificity of CAR-T cell therapies for solid cancers.

CAR-T cell therapies have been successful in treating numerous hematologic malignancies as the T cell can be engineered to target a specific antigen associated with the disease. However, translating CAR-T cell therapies for solid cancers is proving more challenging due to the lack of truly tumor-associated antigens and the high risk of off-target toxicities. To combat this, numerous synthetic biology mechanisms are being incorporated to create safer and more specific CAR-T cells that can be spatiotemporally controlled with increased precision. Here, we seek to summarize and analyze the advancements for CAR-T cell therapies with respect to clinical implementation, from the perspective of synthetic biology and immunology. This review should serve as a resource for further investigation and growth within the field of personalized cellular therapies.

Ecological habitat partitioning and feeding specialisations of coastal minke whales (Balaenoptera acutorostrata) using a recently designated MPA in northeast Scotland.

In the design of protected areas for cetaceans, spatial maps rarely take account of the life-history and behaviour of protected species relevant to their spatial ambit, which may be important for their management. In this study, we examined the distribution and feeding behaviours of adult versus juvenile minke whales (Balaenoptera acutorostrata) from long-term studies in the Moray Firth in northeast Scotland, where a Marine Protected Area (MPA) has recently been designated. Data were collected during dedicated boat surveys between 2001 and 2022 inclusive, from which 784 encounters with 964 whales of confirmed age-class (471 juveniles and 493 adults) were recorded from 56,263 km of survey effort, resulting in 238 focal follows. Adults and juveniles were occasionally seen together, but their distributions were not statistically correlated, and GIS revealed spatial separation / habitat partitioning by age-class-with juveniles preferring shallower, inshore waters with sandy-gravel sediments, and adults preferring deeper, offshore waters with greater bathymetric slope. GAMs suggested that the partitioning between age-classes was predominantly based on the differing proximity of animals to the shore, with juveniles showing a preference for the gentlest seabed slopes, and both adults and juveniles showing a similar preference for sandy gravel sediment types. However, the GAMs only used sightings data with available survey effort (2008 to 2022) and excluded depth due to collinearity issues. Whilst adult minkes employed a range of "active" prey-entrapment specialisations, showing inter-individual variation and seasonal plasticity in their targeted prey, juveniles almost exclusively used "passive" (low energy) feeding methods targeting low-density patches of inshore prey. These findings corroborate the need to incorporate demographic and behavioural data into spatial models when identifying priority areas for protected cetacean species. Not all areas within an MPA have equal value for a population and a better knowledge of the spatial preferences of these whales within the designated Scottish MPAs, appointed for their protection, is considered vital for their conservation.

Automated Analysis of PD1 and PDL1 Expression in Lymph Nodes and the Microenvironment of Transmissible Tumors in Tasmanian Devils.

The wild Tasmanian devil (Sarcophilus harrisii) population has suffered a devastating decline due to two clonal transmissible cancers. The first devil facial tumor 1 (DFT1) was observed in 1996, followed by a second genetically distinct transmissible tumor, the devil facial tumor 2 (DFT2), in 2014. DFT1/2 frequently metastasize, with lymph nodes being common metastatic sites. MHC-I downregulation by DFT1 cells is a primary means of evading allograft immunity aimed at polymorphic MHC-I proteins. DFT2 cells constitutively express MHC-I, and MHC-I is upregulated on DFT1/2 cells by interferon gamma, suggesting other immune evasion mechanisms may contribute to overcoming allograft and anti-tumor immunity. Human clinical trials have demonstrated PD1/PDL1 blockade effectively treats patients showing increased expression of PD1 in tumor draining lymph nodes, and PDL1 on peritumoral immune cells and tumor cells. The effects of DFT1/2 on systemic immunity remain largely uncharacterized. This study applied the open-access software QuPath to develop a semiautomated pipeline for whole slide analysis of stained tissue sections to quantify PD1/PDL1 expression in devil lymph nodes. The QuPath protocol provided strong correlations to manual counting. PD-1 expression was approximately 10-fold higher than PD-L1 expression in lymph nodes and was primarily expressed in germinal centers, whereas PD-L1 expression was more widely distributed throughout the lymph nodes. The density of PD1 positive cells was increased in lymph nodes containing DFT2 metastases, compared to DFT1. This suggests PD1/PDL1 exploitation may contribute to the poorly immunogenic nature of transmissible tumors in some devils and could be targeted in therapeutic or prophylactic treatments.Abbreviations: PD1: programmed cell death protein 1; PDL1: programmed death ligand 1; DFT1: devil facial tumor 1; DFT2: devil facial tumor 2; DFTD: devil facial tumor disease; MCC: Matthew's correlation coefficient; DAB: diaminobenzidine; ROI: region of interest.

Molecular Hydrogen: Is This a Viable New Treatment for Plants in the UK?

Despite being trialed in other regions of the world, the use of molecular hydrogen (H2) for enhanced plant growth and the postharvest storage of crops has yet to be widely accepted in the UK. The evidence that the treatment of plants and plant products with H2 alleviates plant stress and slows crop senescence continues to grow. Many of these effects appear to be mediated by the alteration of the antioxidant capacity of plant cells. Some effects seem to involve heme oxygenase, whilst the reduction in the prosthetic group Fe3+ is also suggested as a mechanism. Although it is difficult to use as a gaseous treatment in a field setting, the use of hydrogen-rich water (HRW) has the potential to be of significant benefit to agricultural practices. However, the use of H2 in agriculture will only be adopted if the benefits outweigh the production and application costs. HRW is safe and relatively easy to use. If H2 gas or HRW are utilized in other countries for agricultural purposes, it is tempting to suggest that they could also be widely used in the UK in the future, particularly for postharvest storage, thus reducing food waste.

Molecular hydrogen in agriculture.

MAIN CONCLUSION: H2 gas, usually in the form of H2-saturated water, could play a useful role in improving many aspects of plant growth and productivity, including resistance to stress tolerance and improved post-harvest durability. Therefore, molecular hydrogen delivery systems should be considered as a valuable addition within agricultural practice. Agriculture and food security are both impacted by plant stresses, whether that is directly from human impact or through climate change. A continuously increasing human population and rising food consumption means that there is need to search for agriculturally useful and environment friendly strategies to ensure future food security. Molecular hydrogen (H2) research has gained momentum in plant and agricultural science owing to its multifaceted and diverse roles in plants. H2 application can mitigate against a range of stresses, including salinity, heavy metals and drought. Therefore, knowing how endogenous, or exogenously applied, H2 enhances the growth and tolerance against numerous plant stresses will enhance our understanding of how H2 may be useful for future to agriculture and horticulture. In this review, recent progress and future implication of H2 in agriculture is highlighted, focusing on how H2 impacts on plant cell function and how it can be applied for better plant performance. Although the exact molecular action of H2 in plants remains elusive, this safe and easy to apply treatment should have a future in agricultural practice.

Downstream Signalling from Molecular Hydrogen.

Molecular hydrogen (H2) is now considered part of the suite of small molecules that can control cellular activity. As such, H2 has been suggested to be used in the therapy of diseases in humans and in plant science to enhance the growth and productivity of plants. Treatments of plants may involve the creation of hydrogen-rich water (HRW), which can then be applied to the foliage or roots systems of the plants. However, the molecular action of H2 remains elusive. It has been suggested that the presence of H2 may act as an antioxidant or on the antioxidant capacity of cells, perhaps through the scavenging of hydroxyl radicals. H2 may act through influencing heme oxygenase activity or through the interaction with reactive nitrogen species. However, controversy exists around all the mechanisms suggested. Here, the downstream mechanisms in which H2 may be involved are critically reviewed, with a particular emphasis on the H2 mitigation of stress responses. Hopefully, this review will provide insight that may inform future research in this area.

Hydrogenases and the Role of Molecular Hydrogen in Plants.

Molecular hydrogen (H2) has been suggested to be a beneficial treatment for a range of species, from humans to plants. Hydrogenases catalyze the reversible oxidation of H2, and are found in many organisms, including plants. One of the cellular effects of H2 is the selective removal of reactive oxygen species (ROS) and reactive nitrogen species (RNS), specifically hydroxyl radicals and peroxynitrite. Therefore, the function of hydrogenases and the action of H2 needs to be reviewed in the context of the signalling roles of a range of redox active compounds. Enzymes can be controlled by the covalent modification of thiol groups, and although motifs targeted by nitric oxide (NO) can be predicted in hydrogenases sequences it is likely that the metal prosthetic groups are the target of inhibition. Here, a selection of hydrogenases, and the possibility of their control by molecules involved in redox signalling are investigated using a bioinformatics approach. Methods of treating plants with H2 along with the role of H2 in plants is also briefly reviewed. It is clear that studies report significant effects of H2 on plants, improving growth and stress responses, and therefore future work needs to focus on the molecular mechanisms involved.

Herbal Teas and their Health Benefits: A Scoping Review.

Herbal teas are used as therapeutic vehicles in many forms of traditional medicine and are a popular global beverage. The purpose of this scoping review was to examine the evidence relating to the clinical efficacy and safety of herbal teas, and to identify the main research themes and gaps in knowledge to inform further work. A scoping review methodology was followed that set out the research question and described the sourcing, selection and analysis of studies. Overall, a total of 145 research publications were retrieved from global bibliographic databases, and after applying exclusion criteria, 21 remained. These studies looked at herbal tea use in female health, diabetes, heart disease and weight loss, with plant species including lavender, chamomile, fenugreek, stinging nettle, spearmint, hibiscus, yerba maté, echinacea and combinations of herbs. Observational studies explored associations between herbal tea consumption and cancer risk, liver health, and the risks linked to the consumption of environmental contaminants in the plant material. Despite plant materials being the basis for drug discovery, and the popularity of herbal teas, the number of articles exploring clinical efficacy and safety is small. In this review we discuss how herbal teas may be beneficial in some areas of clinical and preventative health, and what further research is required to understand whether regular consumption can contribute to healthy living more generally.