Rapid Synthesis and Evaluation of Resveratrol-Piperazine Cocrystals by Ultrasound and Microwave Methods.

OBJECTIVE: Resveratrol-piperazine cocrystals have been obtained by ultrasound (US) and microwave-assisted (MW) techniques, using the solution and slurry-based methods, to study the influence of the synthesis method on the resulting cocrystal properties, and scalability of the processes. The potential of these cocrystals is represented by the unique properties of their components, resveratrol, and piperazine, which could be also used in veterinary practice. Resveratrol has antimicrobial, antiviral and anticarcinogenic properties, while piperazine can be used in the treatment of parasitic infections. METHODS: The influence of ultrasound and microwave-assisted treatment was studied by varying synthesis parameters such as reaction time, temperature, and US or MW power. The main advantage of using these methods is represented by shorter synthesis time compared to conventional methods, resulting in the direct formation of the cocrystals. RESULTS: All samples were obtained in high purity, above 97%. Cocrystal yield correlated positively with ultrasound reaction time, while temperature was not found to influence the microwave synthesis yield up to 50°C, in the case of solution-based methods. MW and US-assisted solution-based methods lead to yields between 52.9 and 68.1%. In the case of the slurry-based method, a minimum reaction time of 5 min leads to the formation of cocrystals with high purity. The resveratrol-piperazine cocrystal's solubility and in vitro antibacterial activity were also evaluated, showing promising results. CONCLUSIONS: Ultrasound and microwave-assisted techniques offer a viable alternative for synthesizing resveratrol-piperazine cocrystals with short reaction times, high yield, and purity, suitable for scalable resveratrol-piperazine cocrystals.

Standardized generation of human iPSC-derived hematopoietic organoids and macrophages utilizing a benchtop bioreactor platform under fully defined conditions.

BACKGROUND: There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac). METHODS: We describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks. RESULTS: The continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone. CONCLUSIONS: The novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications.

An up-scaled biotechnological approach for phosphorus-depleted rye bran as animal feed.

Side streams from the milling industry offer excellent nutritional properties for animal feed; yet their use is constrained by the elevated phosphorus (P) content, mainly in the form of phytate. Biotechnological P recovery fosters sustainable P management, transforming these streams into P-depleted animal feed through enzymatic hydrolysis. The enzymatic P mobilization not only enables P recovery from milling by-products but also supports the valorization of these streams into P-depleted animal feeds. Our study presents the scalability and applicability of the process and characterizes the resulting P-depleted rye bran as animal feed component. Batch mode investigations were conducted to mobilize P from 100 g to 37.1 kg of rye bran using bioreactors up to 400 L. P reductions of 89% to 92% (reducing from 12.7 gP/kg to 1.41-1.28 gP/kg) were achieved. In addition, High Performance Ion Chromatography (HPIC) analysis showed complete depletion of phytate. The successful recovery of the enzymatically mobilized P from the process wastewater by precipitation as struvite and calcium hydrogen phosphate is presented as well, achieving up to 99% removal efficiency. Our study demonstrates a versatile process that is easily adaptable, allowing for a seamless implementation on a larger scale.

Up-scaling a Sol-Gel Process for the Production of a Multi-Component Xerogel Powder.

A sol-gel process for the synthesis of a multi-component oxide material from the system SiO2-ZrO2-Al2O3underwent optimization and up-scaling. Initially, on a laboratory scale, components including precursors, catalysts, and additives were methodically evaluated to ensure a safe and efficient transition to larger volumes. Subsequently, the equipment for the whole setup of the sol-gel process was strategically selected. Leveraging insights from these optimizations, the process was successfully scaled-up to pilot-scale operation, conducting hydrolysis, condensation reactions, gelation, aging, and drying within a single, integrated conical dryer system for an 80 L batch. A visual test and FTIR spectroscopy were applied for process control and monitoring.

Linkages between the concept of nature-based solutions and the notion of landscape.

As the effects of Nature-based solutions (NBS) application are usually much broader than only the area under the project implementation, it is necessary to capture the impact on these actions of landscape as well as the influence of landscape type on the NBS effectiveness. The main aim of this study was to detect linkages between the operational of NBS and the landscape dimention, based on a systematic literature review. The results showed the existence of seven linkages: (1, 2) 'input' and 'output' resulting from the consideration of landscape as a scale of NBS implementation; (3, 4) 'stimulator' and 'inspiration' based on the contribution of landscape-based management to the implementation of NBS; (5) 'co-beneficiary' since the implementation of NBS affects aesthetic dimensions of landscape; (6) 'tool' as landscape-based indicators are used to assess the impacts of NBS; and (7) 'foundation' as health-supporting landscapes may be considered as a type of NBS action.

Cell-free DNA extraction from urine of lung cancer patients and healthy individuals: Evaluation of a simple method using sample volume up-scaling.

BACKGROUND: Urine holds promise as a source for cell-free DNA (cfDNA) analysis of cancer genetics due to its nature as a self-collectable biospecimen available in large quantities. However, pre-analytical variables such as preservation of cfDNA or efficiency of up-scaling specimen volume need to be better explored to increase analysis sensitivity. PATIENTS AND METHODS: Initially effects of pH levels on cfDNA stability of urine preserved with EDTA were investigated in three healthy probands. Furthermore, the efficiency of urine volume up-scaling was examined using a simple DNA extraction method and cfDNA in urine of 32 individuals. Quantification was performed by PCR detection of three relevant targets used for EGFR and KRAS gene mutational analysis. RESULTS: Only samples preserved with EDTA at alkaline pH levels showed cfDNA stability of up to 10 days at room temperature. Moreover, it was found that increasing the volume up to 100 mL was highly efficient. A similar amount of copies was detected in three different gene sites in all specimens indicating both a good availability and a non-random distribution pattern across genes. Since the median cfDNA copy number was 1642 copies/mL, abundance of cfDNA in this type of liquid biopsy is low. CONCLUSION: Predictable sensitivities with different urine volumes on the ground of detectable cfDNA in our study population revealed that up-scaling (>5 mL) is mandatory if the mutation allele frequency is less than 1%.

A circular bioprocess application of algal-based substrate for Bacillus subtilis natto production of γ-PGA.

Poly-γ-glutamic acid (γ-PGA) is a bio-derived water-soluble, edible, hydrating, non-immunogenic polymer. Bacillus subtilis natto is a wild-type γ-PGA producer originally isolated from Japanese fermented natto beans whose activity has been shown to be enhanced through ion-specific activation of Extrachromosomal DNA maintenance mechanisms. Being a GRAS γ-PGA producer, this microorganism has attracted great interest in its use within an industrial context. Here we successfully synthesised amorphous, crystalline and semi-crystalline γ-PGA between 11-27 g/L. In line with circular economy principles, scalable macroalgal biomass has been evaluated as substrate for γ-PGA, displaying great potential in both yields and material composition. In this study whole cell, freeze dried seaweed -namely Laminaria digitata, Saccharina latissima and Alaria esculenta-were pre-treated by means of mechanical methods, sterilised and subsequently inoculated with B. subtilis natto. High shear mixing was found to be the most suitable pre-treatment technique. Supplemented L. digitata (9.1 g/L), S. latissima (10.2 g/L), A. esculenta (13 g/L) displayed γ-PGA yields comparable to those of standard GS media (14.4 g/L). Greatest yields of pure γ-PGA were obtained during the month of June for L. digitata (Avg. 4.76 g/L) comparable to those obtained with GS media (7.0 g/L). Further, pre-treated S. latissima and L. digitata complex media enabled for high molar mass (4,500 kDa) γ-PGA biosynthesis at 8.6 and 8.7 g/L respectively. Compared to standard GS media, algal derived γ-PGA displayed significantly higher molar masses. Further studies will be necessary to further evaluate the impact of varying ash contents upon the stereochemical properties and modify the properties of algal media based γ-PGA with the aid of key nutrients; however, the material synthesised to date can directly displace a number of fossil fuel derived chemicals in drug delivery applications, cosmetics, bioremediation, wastewater treatment, flocculation and as cryoprotectants.

Building a circular economy around poly(D/L-γ-glutamic acid)- a smart microbial biopolymer.

Bio-derived materials have long been harnessed for their potential as backbones of biodegradable constructs. With increasing understanding of organismal biochemistry and molecular genetics, scientists are now able to obtain biomaterials with properties comparable to those achieved by the petroleum industry. Poly-γ-glutamic acid (γ-PGA) is an anionic pseudopolypeptide produced and secreted by several microorganisms, especially Bacillus species. γ-PGA is polymerised via the pgs intermembrane enzymatic complex expressed by many bacteria (including GRAS member - Bacillus subtilis). γ-PGA can exist as a homopolymer of L- glutamic acid or D- glutamic acid units or it can be a co-polymer comprised of D and L enantiomers. This non-toxic polymer is highly viscous, soluble, biodegradable and biocompatible. γ-PGA is also an example of versatile chiral-polymer, a characteristic that draws great attention from the industry. Increased understanding in the correlation between microbial genetics, substrate compositions, fermentation conditions and polymeric chemical characteristics have led to bioprocess optimisation to provide cost competitive, non-petroleum-based, biodegradable solutions. This review presents detailed insights into microbial synthesis of γ-PGA and summaries current understanding of the correlation between genetic makeup of γ-PGA-producing bacteria, range of culture cultivation conditions, and physicochemical properties of this incredibly versatile biopolymer. Additionally, we hope that review provides an updated overview of findings relevant to sustainable and cost-effective biosynthesis of γ-PGA, with application in medicine, pharmacy, cosmetics, food, agriculture and for bioremediation.

Development and Up-Scaling of Electrochemical Production and Mild Thermal Reduction of Graphene Oxide.

To reduce the global emissions of CO2, the aviation industry largely relies on new light weight materials, which require multifunctional coatings. Graphene and its derivatives are particularly promising for combining light weight applications with functional coatings. Although they have proven to have outstanding properties, graphene and its precursor graphene oxide (GO) remain far from application at the industrial scale since a comprehensive protocol for mass production is still lacking. In this work, we develop and systematically describe a sustainable up-scaling process for the production of GO based on a three-step electrochemical exfoliation method. Surface characterization techniques (XRD, XPS and Raman) allow the understanding of the fast exfoliation rates obtained, and of high conductivities that are up to four orders of magnitude higher compared to GO produced via the commonly used modified Hummers method. Furthermore, we show that a newly developed mild thermal reduction at 250 °C is sufficient to increase conductivity by another order of magnitude, while limiting energy requirements. The proposed GO powder protocol suggests an up-scaling linear relation between the amount of educt surface and volume of electrolyte. This may support the mass production of GO-based coatings for the aviation industry, and address challenges such as low weight, fire, de-icing and lightning strike protection.

A critical review on microbial carbonate precipitation via denitrification process in building materials.

The naturally occurring biomineralization or microbially induced calcium carbonate (MICP) precipitation is gaining huge attention due to its widespread application in various fields of engineering. Microbial denitrification is one of the feasible metabolic pathways, in which the denitrifying microbes lead to precipitation of carbonate biomineral by their basic enzymatic and metabolic activities. This review article explains all the metabolic pathways and their mechanism involved in the MICP process in detail along with the benefits of using denitrification over other pathways during MICP implementation. The potential application of denitrification in building materials pertaining to soil reinforcement, bioconcrete, restoration of heritage structures and mitigating the soil pollution has been reviewed by addressing the finding and limitation of MICP treatment. This manuscript further sheds light on the challenges faced during upscaling, real field implementation and the need for future research in this path. The review concludes that although MICP via denitrification is an promising technique to employ it in building materials, a vast interdisciplinary research is still needed for the successful commercialization of this technique.

Leaf and Community Photosynthetic Carbon Assimilation of Alpine Plants Under in-situ Warming.

The Tibetan Plateau is highly sensitive to elevated temperatures and has experienced significant climate warming in the last decades. While climate warming is known to greatly impact alpine ecosystems, the gas exchange responses at the leaf and community levels to climate warming in alpine meadow ecosystems remain unclear. In this study, the alpine grass, Elymus nutans, and forb, Potentilla anserina, were grown in open-top chambers (OTCs) for 3 consecutive years to evaluate their response to warming. Gas exchange measurements were used to assess the effects of in-situ warming on leaf- and community-level photosynthetic carbon assimilation based on leaf photosynthetic physiological parameters. We introduced a means of up-scaling photosynthetic measurements from the leaf level to the community level based on six easily measurable parameters, including leaf net photosynthetic rate, fresh leaf mass per unit leaf area, fresh weight of all plant leaves in the community, the percentage of healthy leaves, the percentage of received effective light by leaves in the community, and community coverage. The community-level photosynthetic carbon assimilation and productivity all increased with warming, and the net photosynthetic rate at the leaf level was significantly higher than at the community level. Under elevated temperature, the net photosynthetic rate of E. nutans decreased, while that of P. anserina increased. These results indicated that climate warming may significantly influence plant carbon assimilation, which could alter alpine meadow community composition in the future.

Body mass Index of children and adolescent participants in a voucher program designed to incentivise participation in sport and physical activity: A cross-sectional study.

There has been limited population-level success in tackling overweight and obesity. The Active Kids program is a universal intervention that aims to increase participation in structured physical activity and sport among children and adolescents in New South Wales (NSW), Australia. This study examined the prevalence of overweight and obesity across subgroups and by social disadvantage in this large broadly representative sample. A cross-sectional study was conducted including all children (n = 671,375) who registered for an Active Kids Program voucher in 2018. The child's height and weight were obtained from an online registration form. Among children and adolescents who registered in the Active Kids Program, the prevalence of overweight and obesity was 17.2% and 7.6%, respectively. A large number of children and adolescents who lived in the most disadvantaged areas (n = 99,583; 14.8%) registered for the program. There was a clear socio-economic gradient for obesity prevalence across areas of increasing disadvantage, with children and adolescents living in the most disadvantaged area being 1.87 (95% CIs 1.82, 1.93) times more likely to be overweight or obese. The Active Kids program successfully reached a substantial proportion of children who are overweight and obese from socio-economically disadvantaged areas, providing financial support and opportunities for these children to participate in structured sport and physical activity. However, the program did not reach all children, and additional physical activity promotion strategies may be needed in a comprehensive approach. Nonetheless, these findings support government investment in reaching children who are overweight or obese with large-scale programs.

Up-Scaling of Thermomechanically Induced Laves Phase Precipitation in High Performance Ferritic (HiperFer) Stainless Steels.

Fully ferritic stainless steels, strengthened by Laves phase precipitates, were developed for high-temperature application in the next generation of ultra-super-critical thermal power plants. Based on the rapid occurrence of thermomechanically induced precipitation in strengthening Laves phase particles, a novel thermomechanical process route for this class of steels was developed. A controlled precipitation of particles, in a desired morphology and quantity, and an optimization of the corresponding forging parameters was achieved on a laboratory scale. This article outlines the very first up-scaling experiment with these optimized forging parameters from the laboratory scale to the industrial scale. The precipitation behavior was analyzed, utilizing digital particle analysis of scanning electron microscopy (SEM) images, to estimate and compare the phase fraction of the precipitated Laves phase, as well as the particle size and distribution. Due to the up-scaling in the forging process, the behavior of the precipitation changed and the precipitation strengthening effect was decreased, in comparison with the laboratory scale.

Detoxification of oil refining effluents by oxidation of naphthenic acids using TAML catalysts.

The environmental problem stemming from toxic and recalcitrant naphthenic acids (NAs) present in effluents from the oil industry is well characterized. However, despite the numerous technologies evaluated for their destruction, their up-scaling potential remains low due to high implementation and running costs. Catalysts can help cutting costs by achieving more efficient reactions with shorter operating times and lower reagent requirements. Therefore, we have performed a laboratory investigation to assess iron-TAML (tetra-amido macrocyclic ligand) activators to catalyze the oxidation of NAs by activating hydrogen peroxide - considered environmentally friendly because it releases only water as by-product - under ultra-dilute conditions. We tested Fe-TAML/H2O2 systems on (i) model NAs and (ii) a complex mixture of NAs in oil refining wastewater (RWW) obtained from a refining site in Colombia. Given the need for cost-effective solutions, this preliminary study explores sub-stoichiometric H2O2 concentrations for NA mineralization in batch mode and, remarkably, delivers substantial removal of the starting NAs. Additionally, a 72-h semi-batch process in which Fe-TAML activators and hydrogen peroxide were added every 8 h achieved 90-95% removal when applied to model NAs (50 mg L-1) and a 4-fold reduction in toxicity towards Aliivibrio fischeri when applied to RWW. Chemical characterization of treated RWW showed that Fe-TAML/H2O2 treatment (i) reduced the concentration of the highly toxic O2 NAs, (ii) decreased cyclized constituents in the mixture, and (iii) preferentially degraded higher molecular weight species that are typically resistant to biodegradation. The experimental findings, together with the recent development of new TAML catalysts that are far more effective than the TAML catalysts deployed herein, constitute a foundation for cost-effective treatment of NA-contaminated wastewater.

Microfluidic Assembly: An Innovative Tool for the Encapsulation, Protection, and Controlled Release of Nutraceuticals.

Nutraceuticals have been gradually accepted as food ingredients that can offer health benefits and provide protection against several diseases. It is widely accepted due to potential nutritional benefits, safety, and therapeutic effects. Most nutraceuticals are vulnerable to the changes in the external environment, which leads to poor physical and chemical stability and absorption. Several researchers have designed various encapsulation technologies to promote the use of nutraceuticals. Microfluidic technology is an emerging approach which can be used for nutraceutical delivery with precise control. The delivery systems using microfluidic technology have obtained much interest in recent years. In this review article, we have summarized the recently introduced nutraceutical delivery platforms including emulsions, liposomes, microspheres, microgels, and polymer nanoparticles based on microfluidic techniques. Emphasis has been made to discuss the advantages, preparations, characterizations, and applications of nutraceutical delivery systems. Finally, the challenges, several up-scaling methods, and future expectations are discussed.

Cellulose nanofibrils and silver nanowires active coatings for the development of antibacterial packaging surfaces.

An active ink composed of cellulose nanofibrils and silver nanowires was deposited on flexible and transparent polymer films using the bar coating process, achieving controlled thicknesses ranging from 200 nm up to 2 µm. For 350 nm thick coating on polyethylene terephthalate films, high transparency (75.6% transmittance) and strong reduction of bacterial growth equal to 89.3% and 100% was noted respectively against Gram-negative Escherichia Coli and Gram-positive Staphylococcus Aureus bacteria using AATCC contact active standard test. Retained antibacterial activity was found with films produced by reverse gravure roll-to-roll process, showing the promising capability of this antibacterial solution to be deployed industrially. Finally, the same ink was also deposited on polylactic acid substrate to investigate barrier properties: for 350 nm thick coating, a reduction of 49% of oxygen transmission rate (dry conditions) and 47% reduction of water vapor transmission rate was noted, proving the enhanced barrier properties of the coatings.

Lab and Pilot-Scale Synthesis of MxOm@SiC Core-Shell Nanoparticles.

The addition of light ceramic particles to bulk technological materials as reinforcement to improve their mechanical properties has attracted increasing interest in the last years. The metal matrix composites obtained using nanoparticles have been reported to exhibit an improvement of their properties due to the decrease in the size of the ceramic additives to the nanoscale. Additionally, important effects such as the dispersion of the nanoparticles, wettability, and low reactivity can be controlled by the modification of the nanoparticles' surface. In this work, we present the preparation of core-shell MxOm@SiC nanoparticles with different shell compositions. The accurate and reproducible preparation is developed both at the lab and pilot scale. The synthesis of these core-shell nanoparticles and their scale-up production are fundamental steps for their industrial use as additives in metal matrix composites and alloys. Powder X-ray diffraction and energy dispersive X-ray (EDX) coupled with scanning transmission electron microscopy (STEM) are used to corroborate the formation of the core-shell systems, whereas line scan-EDX analysis allows measuring the average shell thickness.

Towards universal health coverage: what are the system requirements for effective large-scale community health worker programmes?

Against the background of efforts to strengthen health systems for universal health coverage and health equity, many African countries have been relying on lay members of the community, often referred to as community health workers (CHWs), to deliver primary healthcare services. Growing demand and great variability in definitions, roles, governance and funding of CHWs have prompted the need to revisit CHW programmes and provide guidance on the implementation of successful programmes at scale. Drawing on the synthesised evidence from two extensive literature reviews, this article determines foundational elements of functioning CHW programmes, focusing in particular on the systems requirements of large-scale programmes. It makes recommendations for the effective development of large-scale CHW programmes. The key foundational elements of successful CHW programmes identified are (1) embeddedness, connectivity and integration into the larger system of healthcare service delivery; (2) cadre differentiation and role clarity in order to maintain clear scopes of work and accountability; (3) sound programme design based on local contextual factors and effective people management; and (4) ongoing monitoring, learning and adapting based on accurate and timely local data in order to ensure optimal fit to local context since one size does not fit all. We conclude that CHWs are an investment in health systems strengthening and community resilience with enormous potential for contributing to universal health coverage and the sustainable development goals if well designed and managed. While the evidence base is uneven and mixed, it provides extensive insight and knowledge to strengthen, scale up and sustain CHW programmes throughout Africa.

Application of Microfluidics in the Production and Analysis of Food Foams.

Emulsifiers play a key role in the stabilization of foam bubbles. In food foams, biopolymers such as proteins are contributing to long-term stability through several effects such as increasing bulk viscosity and the formation of viscoelastic interfaces. Recent studies have identified promising new stabilizers for (food) foams and emulsions, for instance biological particles derived from water-soluble or water-insoluble proteins, (modified) starch as well as chitin. Microfluidic platforms could provide a valuable tool to study foam formation on the single-bubble level, yielding mechanistic insights into the formation and stabilization (as well as destabilization) of foams stabilized by these new stabilizers. Yet, the recent developments in microfluidic technology have mainly focused on emulsions rather than foams. Microfluidic devices have been up-scaled (to some extent) for large-scale emulsion production, and also designed as investigative tools to monitor interfaces at the (sub)millisecond time scale. In this review, we summarize the current state of the art in droplet microfluidics (and, where available, bubble microfluidics), and provide a perspective on the applications for (food) foams. Microfluidic investigations into foam formation and stability are expected to aid in optimization of stabilizer selection and production conditions for food foams, as well as provide a platform for (large-scale) production of monodisperse foams.

Computational models of memory consolidation and long-term synaptic plasticity during sleep.

The brain stores memories by persistently changing the connectivity between neurons. Sleep is known to be critical for these changes to endure. Research on the neurobiology of sleep and the mechanisms of long-term synaptic plasticity has provided data in support of various theories of how brain activity during sleep affects long-term synaptic plasticity. The experimental findings - and therefore the theories - are apparently quite contradictory, with some evidence pointing to a role of sleep in the forgetting of irrelevant memories, whereas other results indicate that sleep supports the reinforcement of the most valuable recollections. A unified theoretical framework is in need. Computational modeling and simulation provide grounds for the quantitative testing and comparison of theoretical predictions and observed data, and might serve as a strategy to organize the rather complicated and diverse pool of data and methodologies used in sleep research. This review article outlines the emerging progress in the computational modeling and simulation of the main theories on the role of sleep in memory consolidation.