From discovery to innovation in animal health: Maturing emerging technologies for industrial development.

The Discovery to Innovation in Animal Health Conference (DIAH) was organised to bridge the gap between early developers, including academia, regulators, research organizations, and spin-offs/start-ups on one side, and medium-to large-sized companies on the other. The DIAH Conference confronted and aligned vision from academia, industry and regulators, emphasizing the need for early collaboration, careful IP management, and strategic planning for successful product development and partnerships. Recent breakthroughs in vaccinology have not only accelerated the vaccine production process but have also improved antigen quality significantly. These novel technologies are likely to transform vaccine development and play a crucial role in addressing both immediate health challenges (such as cancer vaccines) and ensuring preparedness for future pandemics. The potential and pitfalls of leveraging AI to drive forward R&I activities in the field of animal health were also discussed. Researchers and entrepreneurs looking for collaboration or investment presented a series of new technologies and start-ups, respectively. A market analysis showed that the animal health industry, while highly consolidated, also shows great diversity, ranging from big pharma to companies offering diagnostics, nutritional health services, wearables, feed additives, animal feed and genetic analyses. An analysis of the investment landscape, although subject to external factors, showed that the chances for success are high when good science, a well established regulatory pathways, with a clearly defined market need can be combined with experienced management and a strong investor consortium.

Improving Stability of CO2 Electroreduction by Incorporating Ag NPs in N-Doped Ordered Mesoporous Carbon Structures.

The electroreduction of carbon dioxide (eCO2RR) to CO using Ag nanoparticles as an electrocatalyst is promising as an industrial carbon capture and utilization (CCU) technique to mitigate CO2 emissions. Nevertheless, the long-term stability of these Ag nanoparticles has been insufficient despite initial high Faradaic efficiencies and/or partial current densities. To improve the stability, we evaluated an up-scalable and easily tunable synthesis route to deposit low-weight percentages of Ag nanoparticles (NPs) on and into the framework of a nitrogen-doped ordered mesoporous carbon (NOMC) structure. By exploiting this so-called nanoparticle confinement strategy, the nanoparticle mobility under operation is strongly reduced. As a result, particle detachment and agglomeration, two of the most pronounced electrocatalytic degradation mechanisms, are (partially) blocked and catalyst durability is improved. Several synthesis parameters, such as the anchoring agent, the weight percentage of Ag NPs, and the type of carbonaceous support material, were modified in a controlled manner to evaluate their respective impact on the overall electrochemical performance, with a strong emphasis on operational stability. The resulting powders were evaluated through electrochemical and physicochemical characterization methods, including X-ray diffraction (XRD), N2-physisorption, Inductively coupled plasma mass spectrometry (ICP-MS), scanning electron microscopy (SEM), SEM-energy-dispersive X-ray spectroscopy (SEM-EDS), high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM), STEM-EDS, electron tomography, and X-ray photoelectron spectroscopy (XPS). The optimized Ag/soft-NOMC catalysts showed both a promising selectivity (∼80%) and stability compared with commercial Ag NPs while decreasing the loading of the transition metal by more than 50%. The stability of both the 5 and 10 wt % Ag/soft-NOMC catalysts showed considerable improvements by anchoring the Ag NPs on and into a NOMC framework, resulting in a 267% improvement in CO selectivity after 72 h (despite initial losses) compared to commercial Ag NPs. These results demonstrate the promising strategy of anchoring Ag NPs to improve the CO selectivity during prolonged experiments due to the reduced mobility of the Ag NPs and thus enhanced stability.

Potential business model for a European vaccine R&D infrastructure and its estimated socio-economic impact.

Background: Research infrastructures are facilities or resources that have proven fundamental for supporting scientific research and innovation. However, they are also known to be very expensive in their establishment, operation and maintenance. As by far the biggest share of these costs is always borne by public funders, there is a strong interest and indeed a necessity to develop alternative business models for such infrastructures that allow them to function in a more sustainable manner that is less dependent on public financing. Methods: In this article, we describe a feasibility study we have undertaken to develop a potentially sustainable business model for a vaccine research and development (R&D) infrastructure. The model we have developed integrates two different types of business models that would provide the infrastructure with two different types of revenue streams which would facilitate its establishment and would be a measure of risk reduction. For the business model we are proposing, we have undertaken an ex ante impact assessment that estimates the expected impact for a vaccine R&D infrastructure based on the proposed models along three different dimensions: health, society and economy. Results: Our impact assessment demonstrates that such a vaccine R&D infrastructure could achieve a very significant socio-economic impact, and so its establishment is therefore considered worthwhile pursuing. Conclusions: The business model we have developed, the impact assessment and the overall process we have followed might also be of interest to other research infrastructure initiatives in the biomedical field.

Technology Readiness Levels for vaccine and drug development in animal health: From discovery to life cycle management.

Public research and innovation initiatives in animal health aim to deliver key knowledge, services and products that improve the control of animal infectious diseases and animal welfare to deliver on global challenges including public health threats, environmental concerns and food security. The Technology Readiness Level (TRL) is a popular innovation policy instrument to monitor the maturity of upcoming new technologies in publicly funded research projects. However, while general definition of the 9 levels on the TRL-scale enable uniform discussions of technical maturity across different types of technology, these definitions are very generic which hampers concrete interpretation and application. Here, we aligned innovation pipeline stages as used in the animal health industry for the development of new vaccines or drugs with the TRL scale, resulting in TRL for animal health (TRLAH). This more bespoke scale can help to rationally allocate funding for animal health research from basic to applied research, map innovation processes, monitor progress and develop realistic progress expectations across the time span of a research and innovation project. The TRLAH thus become an interesting instrument to enhance the translation of public research results into industrial and societal innovation and foster public-private partnerships in animal health.

Near-Unity Electrochemical CO2 to CO Conversion over Sn-Doped Copper Oxide Nanoparticles.

Bimetallic electrocatalysts have emerged as a viable strategy to tune the electrocatalytic CO2 reduction reaction (eCO2RR) for the selective production of valuable base chemicals and fuels. However, obtaining high product selectivity and catalyst stability remain challenging, which hinders the practical application of eCO2RR. In this work, it was found that a small doping concentration of tin (Sn) in copper oxide (CuO) has profound influence on the catalytic performance, boosting the Faradaic efficiency (FE) up to 98% for carbon monoxide (CO) at -0.75 V versus RHE, with prolonged stable performance (FE > 90%) for up to 15 h. Through a combination of ex situ and in situ characterization techniques, the in situ activation and reaction mechanism of the electrocatalyst at work was elucidated. In situ Raman spectroscopy measurements revealed that the binding energy of the crucial adsorbed *CO intermediate was lowered through Sn doping, thereby favoring gaseous CO desorption. This observation was confirmed by density functional theory, which further indicated that hydrogen adsorption and subsequent hydrogen evolution were hampered on the Sn-doped electrocatalysts, resulting in boosted CO formation. It was found that the pristine electrocatalysts consisted of CuO nanoparticles decorated with SnO2 domains, as characterized by ex situ high-resolution scanning transmission electron microscopy and X-ray photoelectron spectroscopy measurements. These pristine nanoparticles were subsequently in situ converted into a catalytically active bimetallic Sn-doped Cu phase. Our work sheds light on the intimate relationship between the bimetallic structure and catalytic behavior, resulting in stable and selective oxide-derived Sn-doped Cu electrocatalysts.

Waste-Derived Copper-Lead Electrocatalysts for CO2 Reduction.

It remains a real challenge to control the selectivity of the electrocatalytic CO2 reduction (eCO2R) reaction to valuable chemicals and fuels. Most of the electrocatalysts are made of non-renewable metal resources, which hampers their large-scale implementation. Here, we report the preparation of bimetallic copper-lead (CuPb) electrocatalysts from industrial metallurgical waste. The metal ions were extracted from the metallurgical waste through simple chemical treatment with ammonium chloride, and CuxPby electrocatalysts with tunable compositions were fabricated through electrodeposition at varying cathodic potentials. X-ray spectroscopy techniques showed that the pristine electrocatalysts consist of Cu0, Cu1+ and Pb2+ domains, and no evidence for alloy formation was found. We found a volcano-shape relationship between eCO2R selectivity toward two electron products, such as CO, and the elemental ratio of Cu and Pb. A maximum Faradaic efficiency towards CO was found for Cu9.00Pb1.00, which was four times higher than that of pure Cu, under the same electrocatalytic conditions. In situ Raman spectroscopy revealed that the optimal amount of Pb effectively improved the reducibility of the pristine Cu1+ and Pb2+ domains to metallic Cu and Pb, which boosted the selectivity towards CO by synergistic effects. This work provides a framework of thinking to design and tune the selectivity of bimetallic electrocatalysts for CO2 reduction through valorization of metallurgical waste.

Mapping Composition-Selectivity Relationships of Supported Sub-10 nm Cu-Ag Nanocrystals for High-Rate CO2 Electroreduction.

Colloidal Cu-Ag nanocrystals measuring less than 10 nm across are promising candidates for integration in hybrid CO2 reduction reaction (CO2RR) interfaces, especially in the context of tandem catalysis and selective multicarbon (C2-C3) product formation. In this work, we vary the synthetic-ligand/copper molar ratio from 0.1 to 1.0 and the silver/copper atomic ratio from 0 to 0.7 and study the variations in the nanocrystals' size distribution, morphology and reactivity at rates of ≥100 mA cm-2 in a gas-fed recycle electrolyzer operating under neutral to mildly basic conditions (0.1-1.0 M KHCO3). High-resolution electron microscopy and spectroscopy are used in order to characterize the morphology of sub-10 nm Cu-Ag nanodimers and core-shells and to elucidate trends in Ag coverage and surface composition. It is shown that Cu-Ag nanocrystals can be densely dispersed onto a carbon black support without the need for immediate ligand removal or binder addition, which considerably facilitates their application. Although CO2RR product distribution remains an intricate function of time, (kinetic) overpotential and processing conditions, we nevertheless conclude that the ratio of oxygenates to hydrocarbons (which depends primarily on the initial dispersion of the nanocrystals and their composition) rises 3-fold at moderate Ag atom % relative to Cu NCs-based electrodes. Finally, the merits of this particular Cu-Ag/C system and the recycling reactor employed are utilized to obtain maximum C2-C3 partial current densities of 92-140 mA cm-2 at -1.15 VRHE and liquid product concentrations in excess of 0.05 wt % in 1 M KHCO3 after short electrolysis periods.

Stabilization effects in binary colloidal Cu and Ag nanoparticle electrodes under electrochemical CO2 reduction conditions.

Nanoparticle modified electrodes constitute an attractive way to tailor-make efficient carbon dioxide (CO2) reduction catalysts. However, the restructuring and sintering processes of nanoparticles under electrochemical reaction conditions not only impedes the widespread application of nanoparticle catalysts, but also misleads the interpretation of the selectivity of the nanocatalysts. Here, we colloidally synthesized metallic copper (Cu) and silver (Ag) nanoparticles with a narrow size distribution (<10%) and utilized them in electrochemical CO2 reduction reactions. Monometallic Cu and Ag nanoparticle electrodes showed severe nanoparticle sintering already at low overpotential of -0.8 V vs. RHE, as evidenced by ex situ SEM investigations, and potential-dependent variations in product selectivity that resemble bulk Cu (14% for ethylene at -1.3 V vs. RHE) and Ag (69% for carbon monoxide at -1.0 V vs. RHE). However, by co-deposition of Cu and Ag nanoparticles, a nanoparticle stabilization effect was observed between Cu and Ag, and the sintering process was greatly suppressed at CO2 reducing potentials (-0.8 V vs. RHE). Furthermore, by varying the Cu/Ag nanoparticle ratio, the CO2 reduction reaction (CO2RR) selectivity towards methane (maximum of 20.6% for dense Cu2.5-Ag1 electrodes) and C2 products (maximum of 15.7% for dense Cu1-Ag1 electrodes) can be tuned, which is attributed to a synergistic effect between neighbouring Ag and Cu nanoparticles. We attribute the stabilization of the nanoparticles to the positive enthalpies of Cu-Ag solid solutions, which prevents the dissolution-redeposition induced particle growth under CO2RR conditions. The observed nanoparticle stabilization effect enables the design and fabrication of active CO2 reduction nanocatalysts with high durability.

Heat-labile enterotoxin of Escherichia coli promotes intestinal colonization of Salmonella enterica.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of infantile and travellers' diarrhoea, which poses a serious health burden, especially in developing countries. In addition, ETEC bacteria are a major cause of illness and death in neonatal and recently weaned pigs. The production of a heat-labile enterotoxin (LT) promotes the colonization and pathogenicity of ETEC and may exacerbate co-infections with other enteric pathogens such as Salmonella enterica. We showed that the intraintestinal presence of LT dramatically increased the intestinal Salmonella Typhimurium load in experimentally inoculated pigs. This could not be explained by direct alteration of the invasion or survival capacity of Salmonella in enterocytes, in vitro. However, we demonstrated that LT affects the enteric mucus layer composition in a mucus-secreting goblet cell line by significantly decreasing the expression of mucin 4. The current results show that LT alters the intestinal mucus composition and aggravates a Salmonella Typhimurium infection, which may result in the exacerbation of the diarrhoeal illness.

Enhanced disease resistance in Artemia by application of commercial beta-glucans sources and chitin in a gnotobiotic Artemia challenge test.

The anti-infectious potential of a selection of putative immunostimulants including six commercial beta-glucans (all extracted from baker's yeast Saccharomyces cerevisiae except for Laminarin) and chitin particles were verified in Artemia nauplii by challenging them under gnotobiotic conditions with the pathogen Vibrio campbellii. Under the described experimental conditions, no differential macroscopic nutritional effect (e.g. growth) was observed among the products. Significant increased survival was observed with beta-glucan (Sigma) and Zymosan and to a lesser extent with MacroGard in challenged nauplii. A poor correlation was found between survival values of the challenged Artemia and the product compositions (such as chitin, mannose and beta-glucan content) indicating that the quality of beta-glucans (e.g. the ratio of beta-1,3 and beta-1,6 glucan, the molecular weight, the dimensional structure, type and frequency of branches), eventually in combination with other unidentified compounds, is more important than the amount of product offered. This small-scale testing under gnotobiotic conditions using freshly hatched Artemia nauplii allows for a rapid and simultaneous screening of anti-infectious and/or putative immunostimulatory polymers, and should be combined with studies on cellular and humoral immune responses in order to gain more quantitative insight into their functional properties.

The deposition of conjugated linoleic acids in eggs of laying hens fed diets varying in fat level and fatty acid profile.

The objective of this study was to investigate the incorporation of conjugated linoleic acid (CLA) into eggs and its effect on the fatty acid metabolism when layers are fed diets with different fat sources and fat levels. Layers were fed either a low fat diet (LF) or one of three high fat diets based on soybean oil (SB), animal fat (AF) or flaxseed oil (FSO). CLA was added at a concentration of 1 g/100 g feed from two different CLA premixes with a different CLA profile. For the trial, 144 laying hens were allocated to 12 treatments (4 basal fat sources x 3 CLA treatments) with 3 replicates of 4 hens each. No significant differences were observed in feed intake, egg weight, feed conversion or laying rate between chickens fed control and CLA-supplemented diets. Differences in yolk fat, cholesterol or yolk color were not clearly related to the dietary CLA. However, the supplementation of CLA to the diets had clear effects on the fatty acid composition, i.e., a decrease in monounsaturated fatty acids (MUFA) and an increase in saturated fatty acids (SFA) was observed, whereas the polyunsaturated fatty acids (PUFA) content were essentially unaffected. The results suggest that CLA may influence the activity of the desaturases to a different extent in the synthesis of (n-6) and (n-3) long-chain fatty acids. These effects of CLA depend on the level of (n-6) and (n-3) fatty acids available in the feed. The apparent deposition rate (%) is clearly higher for the c9, t11 isomer than for the t10, c12 isomer. Adding CLA to layers diets rich in (n-3) fatty acids produces eggs that could promote the health of the consumer in terms of a higher intake of (n-3) fatty acids and CLA.