Search

Nucleic acid therapeutics offer a new paradigm to rapidly respond to global health problems. The versatility of nucleic acids, especially in RNA therapies, provides the ability to tune levels of specific protein expression, achieving downregulation through short interfering RNA (siRNA) or upregulation by messenger RNA (mRNA) administration. Recent advances in the development of delivery vehicles, including nonviral nanoparticles are crucial to overcome the innate barriers to nucleic acid delivery. Toward this end, current clinical approaches have utilized mRNA and lipid nanoparticles (LNPs) to address the COVID-19 pandemic through novel vaccine strategies, producing efficacious vaccines within one year of sequencing the SARS-CoV-2 genome. Here, we review fundamental concepts required to achieve successful nucleic acid delivery, including the design of LNP systems optimized for mRNA vaccine applications. Graphic abstract

Increased fluxes of reactive nitrogen (Nr), often associated with N fertilizer use in agriculture, have resulted in negative environmental consequences, including eutrophication, which cost billions of dollars per year globally. To address this, best management practices (BMPs) to reduce Nr loading to the environment have been introduced in many locations. However, improvements in water quality associated with BMP implementation have not always been realised over expected timescales. There is a now a significant body of scientific evidence showing that the dynamics of legacy Nr storage and associated time lags invalidate the assumptions of many models used by policymakers for decision making regarding Nr BMPs. Building on this evidence, we believe that the concepts of legacy Nr storage dynamics and time lags need to be included in these models. We believe the biogeochemical research community could play a more proactive role in advocating for this change through both awareness raising and direct collaboration with policymakers to develop improved datasets and models. We anticipate that this will result in more realistic expectations of timescales for water quality improvements associated with BMPs. Given the need for multi-nutrient policy responses to tackle challenges such as eutrophication, integration of N stores will have the further benefit of aligning both researchers and policymakers in the N community with the phosphorus and carbon communities, where estimation of stores is more widespread. Ultimately, we anticipate that integrating legacy Nr storage dynamics and time lags into policy frameworks will better meet the needs of human and environmental health.

Despite an improvement of water quality across Europe there are many pollution hotspots for both nitrates and PPPs, mainly due to agricultural activities. The BMPs and MMs to reduce pollution from agriculture are well known, and there are policy instruments in place to ensure drinking water standards, but the current approach has not been efficient enough. Within the H2020 Water Protect project the premise was that there is a need for a multi-actor, participatory approach to tackle the issue from a new angle, and to assess why the uptake of known BMPs and MMs was not better among farmers. Seven “Action Labs” were selected that represent major physical, socio-economical, cultural and farming settings across Europe. A methodology of multi-actor engagement was chosen but with different approaches due to the local context. Initially the level of farmers' awareness about water quality issues was matched to the observed uptake rates of BMPs and MMs. In a second survey barriers hindering the uptake of measures were identified. The first survey revealed a low general awareness on the potential pollution to drinking water sources. Despite this, between 24% to 88% of the surveyed farmers per Action Lab were already voluntarily adopting one quarter of the selected BMPs and MMs. The second survey demonstrated the need to address organisational, legislative, sociological and technical barriers. The lack of coordination between different institutional bodies promoting measures and the financial incentives needed to invest and operate these often-costly measures need to be considered. The multi-actor, participatory approach with its improved awareness and collaboration made it possible to identify the crucial factors for improvement - to build a social acceptance among all actors and communicate the issues and solutions from the start.

© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020. Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biological tissues, and the fabrication of cellularized organ and tissue-mimics, among other applications. In this study, we highlight convergent efforts within engineering, cell biology, soft matter, and chemistry in an overview of the 3D bioprinting field, and we then conclude our work with outlooks toward the application of 3D bioprinting for ocular research in vitro and in vivo.

Nucleic acid therapeutics offer a new paradigm to rapidly respond to global health problems. The versatility of nucleic acids, especially in RNA therapies, provides the ability to tune levels of specific protein expression, achieving downregulation through short interfering RNA (siRNA) or upregulation by messenger RNA (mRNA) administration. Recent advances in the development of delivery vehicles, including nonviral nanoparticles are crucial to overcome the innate barriers to nucleic acid delivery. Toward this end, current clinical approaches have utilized mRNA and lipid nanoparticles (LNPs) to address the COVID-19 pandemic through novel vaccine strategies, producing efficacious vaccines within one year of sequencing the SARS-CoV-2 genome. Here, we review fundamental concepts required to achieve successful nucleic acid delivery, including the design of LNP systems optimized for mRNA vaccine applications. Graphic abstract

Worldwide dairy processing plants produce high volumes of dairy processing sludge (DPS), which can be converted into secondary derivatives such as struvite, biochar and ash (collectively termed STRUBIAS). All of these products have high fertilizer equivalent values (FEV), but future certification as phosphorus (P)-fertilizers in the European Union will mean they need to adhere to new technical regulations for fertilizing materials i.e., content limits pertaining to heavy metals (Cd, Cu, Hg, Ni, Pb, and Zn), synthetic organic compounds and pathogens. This systematic review presents the current state of knowledge about these bio-based fertilizers and identifies knowledge gaps. In addition, a review and calculation of greenhouse gas emissions from a range of concept dairy sludge management and production systems for STRUBIAS products [i.e., biochar from pyrolysis and hydrochar from hydrothermal carbonization (HTC)] is presented. Results from the initial review showed that DPS composition depends on product type and treatment processes at a given processing plant, which leads to varied nutrient, heavy metal and carbon contents. These products are all typically high in nutrients and carbon, but low in heavy metals. Further work needs to concentrate on examining their pathogenic microorganism and emerging contaminant contents, in addition to conducting an economic assessment of production and end-user costs related to chemical fertilizer equivalents. With respect to STRUBIAS products, contaminants not present in the raw DPS may need further treatment before being land applied in agriculture e.g., heated producing ashes, hydrochar, or biochar. An examination of these products from an environmental perspective shows that their water quality footprint could be minimized using application rates based on P incorporation of these products into nutrient management planning and application by incorporation into the soil. Results from the concept system showed that elimination of

In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD.

In many areas of the globe, the installation of artificial drains on naturally poorly drained soils is a necessary part of farm management. Identifying the location of artificially drained areas is an important step in achieving environmentally sustainable agricultural production. However, in many regions, data on the presence or the distribution of artificial drainage systems are rare. We outline an approach to identify artificially drained soils using Earth observation (EO) satellite imagery and digital elevation data. The method exploits the contrasting phenology of grass during a peak growth stage to identify artificially drained and undrained soils. Two machine-learning techniques, support vector machine and random forest, were tested. Classification accuracy up to 91% was achieved using photo interpreted accuracy points using higher resolution satellite imagery. Additional investigations would be required to establish whether the drained conditions identified were a result of artificial drainage or from naturally well-drained soils occurring within larger soil units. Herein, the Republic of Ireland is used as a test case. Based on our findings, the area of artificially drained grassland within the study area could be revised upward, with 44% (or ∼345; 000 ha) of pasture currently classed as “poorly drained” identified as “artificially drained.” At one location, a change in the modelled drainage condition at field level was demonstrated following drain installation. The presented method demonstrates the ability of EO satellites to quickly and accurately map field drainage status at farm management scales over a wide area. This has the potential to improve management decisions at local scales, but also has implications in terms of national policy development and regulation in areas such as water quality and climate change mitigation

The red seaweed Agarophyton vermiculophyllum is an invasive species native to the north-west Pacific, which has proliferated in temperate estuaries of Europe, North America and Africa. Combining molecular identification tools, historical satellite imagery and one-year seasonal monitoring of biomass and environmental conditions, the presence of A. vermiculophyllum was confirmed, and the invasion was assessed and reconstructed. The analysis of satellite imagery identified the first bloom in 2014 and revealed that A. vermiculophyllum is capable of thriving in areas, where native bloom-forming species cannot, increasing the size of blooms (ca. 10%). The high biomass found during the peak bloom (>2 kg m−2) and the observation of anoxic events indicated deleterious effects. The monitoring of environmental conditions and biomass variability suggests an essential role of light, temperature and phosphorous in bloom development. The introduction of this species could be considered a threat for local biodiversity and ecosystem functioning in a global change context.

Advances in biomaterials for drug delivery are enabling significant progress in biology and medicine. Multidisciplinary collaborations between physical scientists, engineers, biologists, and clinicians generate innovative strategies and materials to treat a range of diseases. Specifically, recent advances include major breakthroughs in materials for cancer immunotherapy, autoimmune diseases, and genome editing. Here, strategies for the design and implementation of biomaterials for drug delivery are reviewed. A brief history of the biomaterials field is first established, and then commentary on RNA delivery, responsive materials development, and immunomodulation are provided. Current challenges associated with these areas as well as opportunities to address long-standing problems in biology and medicine are discussed throughout., National Institutes of Health (Award CA200351), Burroughs Wellcome Fund (Grant 1015145)

Developing strategies to deliver the required dose of therapeutics into target tissues and cell populations within the body is a principal aim of controlled release and drug delivery. Specifically, there is an interest in developing formulations that can achieve drug concentrations within the therapeutic window, for extended periods of time, with tunable release profiles, and with minimal complication and distress for the patient. To date, drug delivery systems have been developed to serve as depots, triggers, and carriers for therapeutics including small molecules, biologics, and cell-based therapies. Notably, the efficacy of these systems is intricately tied to the manner in which they are administered. For example, systemic and oral routes of administration are common, but both can result in rapid clearance from the organism. Towards this end, what formulation and administration route strategies are available to prolong the bioavailability of therapeutics? Here, we discuss historical and modern drug delivery systems, with the intention of exploring how properties including formulation, administration route and chemical structure influence the ability to achieve extended-release drug release profiles within the body.

A photocurable thiol-ene network polymer, poly(limonene thioether) (PLT32o), is synthesized, characterized, fabricated into tissue engineering scaffolds, and demonstrated in vitro and in vivo. Micromolded PLT32o grids exhibit compliant, elastomeric mechanical behavior similar to grids made of poly(glycerol sebacate) (PGS), an established biomaterial. Multilayered PL32o scaffolds with regular, geometrically defined pore architectures support heart cell seeding and culture in a manner similar to multilayered PGS scaffolds. Subcutaneous implantation of multilayered PLT32o scaffolds with cultured heart cells provides long-term 3D structural support and retains the exogenous cells, whereas PGS scaffolds lose both their structural integrity and the exogenous cells over 31 d in vivo. PLT32o membrane implants retain their dry mass, whereas PGS implants lose 70 percent of their dry mass by day 31. Macrophages are initially recruited to PLT32o and PGS membrane implants but are no longer present by day 31. Facile synthesis and processing in combination with the capability to support heart cells in vitro and in vivo suggest that PLT32o can offer advantages for tissue engineering applications where prolonged in vivo maintenance of 3D structural integrity and elastomeric mechanical behavior are required., United States. National Institutes of Health (R01-HL107503)

Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl amino alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve nucleic acid delivery in vivo., National Science Foundation (U.S.). Graduate Research Fellowship Program, Shire Pharmaceuticals, Wellcome Trust-MIT Postdoctoral Fellowship